@article {163315, title = {Acquisitive traits improve seedling survival with reduced soil moisture at the edges of a fragmented tropical forest}, journal = { Plant Ecology }, volume = {227}, year = {2026}, month = { 05 December 202}, type = {Research Article}, abstract = {

Climate change and habitat fragmentation threaten biodiversity, but their interactive effects remain poorly understood. In closed-canopy forests, altered rainfall patterns may induce drought conditions that are exacerbated at forest edges due to warmer, drier microclimates. Plant responses to water limitation can be mediated by functional traits related to resource acquisition and stress tolerance. We examined how reduced soil moisture and edge conditions jointly affect seedling survival, and whether species{\textquoteright} responses are explained by their traits. In a human-modified forest in the central Western Ghats, India, we transplanted ~ 1-year-old seedlings in a factorial combination of habitat (forest edge vs. interior) and moisture deficit (throughfall exclusion vs. control). We monitored survival through one year and estimated moisture response (survival in throughfall exclusion vs. control) and tested its relationship with six traits. Throughfall exclusion reduced soil moisture more at edges, particularly during dry months. At the edge, three species showed significantly lower survival under drought, whereas survival in the interior did not differ with water treatment. Acquisitive traits (low stem specific density, low leaf dry matter content, and low leaf mass per area) improved survival with reduced moisture at edges. Trait-mediated responses were not evident in the interior, likely due to buffered microclimates. Multi-trait combinations were better predictors of moisture response than individual traits, indicating trait coordination. Our results suggest that drier conditions may favour acquisitive species at forest edges, which has implications for community composition, management and restoration of fragmented forests in a changing climate.

}, keywords = {Forest fragmentation, Resource acquisition., Seedling survival, Trait-environment interactions, Tropical forests}, doi = {https://doi.org/10.1007/s11258-025-01577-z}, url = {https://link.springer.com/article/10.1007/s11258-025-01577-z}, author = {Peddiraju Bandaru and Lakshmipriya Cannanbilla and Ashish Nambiar and Rishanth Kuruvankunath Ravi and Ashok Kumar Mani and S Saravanan Karuna Moorthy and Sharath Prakash and Ranjana Gauri Muniraja and Malavika Kamath and Meghna Krishnadas} } @article {166225, title = {Adaptation to extreme stress under the growth-survival fitness trade-off}, journal = {Phys. Rev. E}, volume = {113}, year = {2026}, month = {May}, pages = {054403}, abstract = {

Microbial adaptation to extreme stress, such as starvation, antimicrobial exposure, or freezing, often reveals fundamental trade-offs between survival and proliferation. Understanding how populations navigate these trade-offs in fluctuating environments remains a central challenge. We develop a quantitative model to investigate the adaptation of populations of yeast (Saccharomyces cerevisiae) subjected to cycles of growth and extreme freeze-thaw stress, focusing on the role of quiescence as a mediator of survival. Our model links key life-history traits{\textemdash}growth rate, lag time, quiescence probability, and stress survival{\textemdash}to a single underlying phenotype, motivated by the role of intracellular trehalose in the adaptation of yeast to freeze-thaw stress. Through stochastic population simulations and analytical calculation of the long-term growth rate, we identify the evolutionary attractors of the system. We find that the strength of the growth-survival trade-off depends critically on environmental parameters, such as the duration of the growth phase. Crucially, our analysis reveals that populations optimized for growth-stress cycles can maintain viability alongside growth-optimized populations even in the absence of stress. This demonstrates that underlying physiological trade-offs do not necessarily translate into fitness trade-offs at the population level, providing general insights into the complex interplay between environmental fluctuations, physiological constraints, and evolutionary dynamics.

}, doi = {10.1103/nppw-z5lv}, url = {https://link.aps.org/doi/10.1103/nppw-z5lv}, author = {Chaturvedi, Nandita and Tvishamayi, Charuhansini and Thutupalli, Shashi} } @article {164805, title = {Addressing Gaps in Butterfly Population Monitoring to Catalyze Global Insect Conservation}, journal = {Conservation Letter}, year = {2026}, month = {23 March 2026}, abstract = {

The conservation community sorely lacks a global indicator of change in insect populations. Given widespread insect declines, addressing this gap is key for conservation and policy targets. We suggest that butterfly monitoring programs can serve as the foundation for an effective global network of insect monitoring. To assess this potential, we bring together an international consortium and calculate a {\textquotedblleft}Global Butterfly Index{\textquotedblright} using the Living Planet Index approach. Based on 10,386 population trends of 213 univoltine species, we found that overall declines in butterfly populations are predictable based on species traits. Our effort should pave the way for the development of a global network of butterfly population monitoring schemes. Since butterflies are the best monitored insects and have strong emotional value for the public, a global infrastructure for butterfly monitoring can be a flagship for insect conservation, informing policymaking and spurring societal transitions towards sustainable futures.

}, doi = {10.1111/con4.70037}, url = {https://conbio.onlinelibrary.wiley.com/doi/full/10.1111/con4.70037}, author = {F. Riva and R. Schmucki and R. Cooke and M. Balalaikins and J. M. Barea-Azc{\'o}n and D. N. Basu and M. B{\"o}hm and T. C. Bonebrake and S. Chowdhury and O. Comray and A. O. Debrot and A. J. Dolezal and E. E. Dyer and B. Fontaine and Z. F. Fric and R. Girotra and N. J. B. Isaac and K. R. Nagesh and E. K{\"u}hn and K. Kunte and A. S. Kutt and M. Kuussaari and M. Larivee and N. Legall and V. V. Lien and H. M. Madden and D. Maes and S. P. McGaffin and L. McRae and X. Mestdagh and M. L. Munguira and M. Musche and H. I. Mynott and V. Nawge and G. Peer and L. B. Pettersson and J. Pippen and L. Reis and T. Roth and M. {\v S}a{\v s}i{\'c} and J. Settele and C. Sevilleja and S. Sheikh and M. Sielezniew and R. Solis and C. Stefanescu and N. Titeux and E. Tzirkalli and A. Ubach and C. A. M. van Swaay and A. Walker and B. A. Woodcock and David B. Roy} } @article {163840, title = {The assembly and functions of multiway enhancer-promoter hubs.}, journal = {Curr Opin Genet Dev}, volume = {97}, year = {2026}, month = {2026 Feb 19}, pages = {102446}, abstract = {

Single enhancer-promoter communication, once conceptualized through a simple {\textquoteright}bridge model{\textquoteright} of direct molecular contact, is now redefined by the concept of hubs. The term {\textquoteright}hub{\textquoteright} is often used interchangeably with other nuclear structures and concepts; however, in this review, we define a hub as a spatial cluster of multiple cis-regulatory elements (CREs), including enhancers and promoters, originating from the same or different chromosomes. These hubs represent dynamic and transient assemblies that coordinate regulatory interactions within the three-dimensional nuclear landscape. A variety of partially overlapping mechanisms, including phase-separation, loop extrusion, protein scaffolding, and actin myosin-driven chromatin mobility, have been proposed to facilitate their formation. However, the organizational principles governing these multi-CREs interacting hubs and their roles in orchestrating gene expression programs remain only partially understood. In this review, we synthesize emerging insights into the formation, function, and regulatory architecture of these transcriptional hubs and propose that they confer robustness, coordination, and flexibility to gene regulation across diverse cellular and developmental contexts.

}, issn = {1879-0380}, doi = {10.1016/j.gde.2026.102446}, url = {https://www.sciencedirect.com/science/article/pii/S0959437X26000134?ref=pdf_download\&fr=RR-2\&rr=9d0a84d9df331473}, author = {Islam, Zubairul and Shigvan, Sakshi and Singh, Amanjot and Notani, Dimple} } @article {163323, title = {Bottleneck size drives the evolution of cooperative traits in an aggregative multicellular myxobacterium.}, journal = {PLoS Biol}, volume = {24}, year = {2026}, month = {2026 Jan}, pages = {e3003499}, abstract = {

Repeated population bottlenecks influence the evolution and maintenance of cooperation. However, it remains unclear whether bottlenecks select all cooperative traits expressed by an organism or only a subset of them. Myxococcus xanthus, a social bacterium, displays multiple cooperative traits, including growth, predation, sporulation in multicellular fruiting bodies, and germination. Using laboratory evolution experiments, we investigated the effect of repeated stringent versus relaxed population bottlenecks on the evolution of these four cooperative traits when they were all under selection. We found that only fruiting body formation and growth were positively selected under the stringent regimen, while the other two traits were selected against. The pattern was reversed in the relaxed regimen. Populations propagated under the relaxed regimen also exhibited greater fitness across the entire\ life cycle\ and maintained higher trait variations, including coexistence of cooperative and exploitative strategies. Genomic analyses identified mutations in σ54 interacting protein and DNA binding response regulator protein associated with adaptations in stringent and relaxed regimens, respectively. Furthermore, similar trade-offs, for example, between sporulation and germination, are also seen among natural populations of M. xanthus. Overall, we demonstrate that different bottleneck sizes drive the evolution of cooperative life history traits in distinct ways, often via trade-offs that constrain their joint optimization.

}, keywords = {Bacterial Proteins, Biological Evolution, Mutation, Myxococcus xanthus, Selection, Genetic, Spores, Bacterial}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3003499}, url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003499}, author = {Kalathera, Jyotsna and Jaiswal, Prakhar and Mandal, Neha and Patel, Vishwa and Guttal, Vishwesha and Krishna, Sandeep and Pande, Samay} } @article {164001, title = {BPS2026 {\textendash} Membrane proximal actin cytoskeleton and protein crowding synergistically modulate the mesoscale mobility of membrane components in the cell membrane}, journal = {Biophysical Journal}, volume = {125}, year = {2026}, month = {19 February 2026}, chapter = {235a}, doi = {https://doi.org/10.1016/j.bpj.2025.11.1544 }, url = {https://www.sciencedirect.com/science/article/pii/S0006349525022945?via\%3Dihub}, author = {Sankarshan Talluri and Saurav Varma and Pooja S. Krishna and Abhinav Banerjee and , Meenkashi Iyer and Mahipal Ganji and Sumantra Sarkar and Satyajit Mayor} } @article {164003, title = {BPS2026 {\textendash} PickET: An unsupervised method for localizing macromolecules in cryo-electron tomograms}, journal = {Biophysical Journal}, volume = {125}, year = {2026}, month = {19 February 2026}, chapter = {121a}, author = {Shreyas M. Arvindekar and Omkar Golatkar and Shruthi Viswanath} } @article {163998, title = {Cascade PSI-BLAST 2.0: a fast-searching parallelized remote homology detection tool and development of Cascade web server 2.0}, journal = {Springer Nature Link}, year = {2026}, month = {18 February 2026}, abstract = {

Remote homology detection is critical for inferring evolutionary and functional relationships among proteins, but divergence below 30\% identity often hinders standard sequence-based searches. Profile-based methods and HMMs improve sensitivity, yet many distant homologues remain undetected. Cascade PSI-BLAST uses efficient, iterative, multi-generation searches of intermediate hits to bridge sequence gaps, constructing successive PSSMs that reveal remote relationships without structural information. However, its application to ultra-large databases such as NR and UniProt is computationally intensive. We address this limitation by optimizing intermediate selection and enabling distributed execution across multiple CPUs or servers, significantly enhancing throughput and resource utilization while preserving detection sensitivity.

}, keywords = {Cascade PSI_BLAST, GNU parallel, Parallel processing, PSI BLAST, Remote homology search, Webserver}, doi = {https://doi.org/10.1186/s12859-026-06366-7 }, url = {https://link.springer.com/article/10.1186/s12859-026-06366-7}, author = {Soumya Nayak and Dheemanth Reddy Regati and Murugavel Pavalam and R. Sowdhamini} } @article {164790, title = {Comparative transcriptomic insights into iron deficiency response in contrasting rice varieties at the seedling stage reveal distinct response strategies and identify novel candidate genes}, journal = {Frontiers in Plant Science}, volume = {17}, year = {2026}, month = {12 March 2026}, abstract = {

Iron deficiency is a major constraint in rice cultivation, particularly under direct-seeded rice (DSR) systems, where aerobic soil conditions reduce iron availability in plant-accessible forms. In this study, the experiment was initiated with screening of 116 germplasm lines of two weeks old line under hydroponics iron-deficient and sufficient conditions. Based on morphological and SPAD (Soil Plant Analysis Development) values, two contrasting rice genotypes - RA23 (tolerant) and LalatMas (susceptible) were selected and investigated to determine the molecular basis of iron deficiency response through comparative transcriptome analyses. A substantial number of differentially expressed genes (DEGs) were identified in each genotype, revealing distinct transcriptional reprogramming associated with iron acquisition, transport, and homeostasis. Functional classification and enrichment analyses uncovered genotype-specific regulation of pathways related to iron ion transport, general defense and stimulus-response functions, and ADP-binding activity, indicating the involvement of signaling and regulatory proteins. A subset of candidate genes, including both known iron-responsive regulators and previously uncharacterized proteins, was further prioritized based on differential expression patterns, interaction predictions, structural features and expression profiles. Quantitative real-time PCR validation confirmed the expression patterns of selected DEGs, supporting their relevance in iron stress adaptation. Notably, the greater induction of iron transporters in LalatMas likely reflects its stronger compensatory drive to acquire iron relative to RA23. This study provides the first report of leaf-specific transcriptomic signatures associated with iron deficiency in rice and offers a valuable set of candidate genes for functional analysis and breeding of iron-efficient cultivars optimized for DSR and other nutrient-limited agroecosystems.

}, doi = {10.3389/fpls.2026.1764898}, url = {https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2026.1764898/full}, author = {Ananya Sinha and Mohd Fayaz and Siddharth Panda and Ramanathan Sowdhamini} } @article {166220, title = {Cosolutes Modulate Polyubiquitin Fibrillation}, journal = {ACS Omega}, volume = {11}, year = {2026}, pages = {28004-28014}, abstract = {

Ubiquitin, a 76-residue polypeptide, functions as a post-translational modifier and forms polyubiquitin (polyUb) chains on substrate proteins to activate diverse cellular functions. Ubiquitin is often found in the lesions associated with neurodegenerative disorders like Alzheimer{\textquoteright}s and Huntington{\textquoteright}s disease. It was recently observed that polyubiquitin chains, under in vitro conditions, often form β-sheet-rich fibrillar amyloid aggregates. However, the exact mechanism of conversion from monomer polyUb to amyloid-like fibrils is poorly understood. We report that polyubiquitin forms higher-order oligomeric fibrils and temperature, pH, and ionic strength modulate polyubiquitin (polyUb) fibrillation. Cosolutes such as ionic liquids and macromolecular crowding agents also enhance the aggregation rate. These findings uncover that temperature/cosolutes lower the energy barrier to populate a partially unfolded form (M*), which drives amyloid-like fibril formation. Other factors increase the effective protein concentration of these partially unfolded forms, accelerating aggregation. These insights provide the fundamental basis for ubiquitin chain aggregation, which is necessary to guide the development of therapies and diagnostics.

}, doi = {10.1021/acsomega.5c11883}, url = {https://doi.org/10.1021/acsomega.5c11883}, author = {Acharya, Kalpaja and Ainavarapu, Sri Rama Koti and Das, Ranabir} } @inbook {163322, title = {Cryo-Electron Microscopy in the Study of Protein{\textendash}Protein Interactions}, booktitle = { Computational Approaches in Drug Design }, volume = {42}, year = {2026}, pages = {43-76}, publisher = {Springer, Cham}, organization = {Springer, Cham}, chapter = {Cryo-Electron Microscopy in the Study of Protein{\textendash}Protein Interactions}, abstract = {

Protein{\textendash}protein interactions (PPIs) are fundamental to many biological processes, including signal transduction, gene regulation, maintenance of cellular homeostasis, and immune response. Understanding the molecular details of PPIs is vital for elucidating the mechanisms underlying cellular functions and diseases. Traditionally, techniques such as X-ray crystallography and nuclear magnetic resonance (NMR) have provided valuable structural information about PPIs. However, the investigation of protein complexes that are large, dynamic, flexible, or those associated with membranes has proven difficult to characterize structurally. Cryo-Electron Microscopy (Cryo-EM) and Cryo-Electron Tomography (Cryo-ET) have revolutionized the ability to visualize protein{\textendash}protein interactions increasingly at higher resolution and within cellular context. Despite its strengths, imaging with Electron Microscopy (EM) poses challenges in achieving high-resolution structures for small or heterogeneous complexes and requires substantial computational resources for data processing. Nonetheless, its ability to reveal atomic-level details of protein interactions makes it a crucial tool in structural biology and drug discovery. This chapter reviews recent advances in cryo-EM techniques, particularly in the study of PPIs.

}, keywords = {Cryo-EM, Cryo-ET, Drug discovery., Protein{\textendash}protein interaction, Structural biology}, isbn = {Print ISBN 978-3-032-07879-7}, issn = {Online ISBN 978-3-032-07880-3}, doi = {https://doi.org/10.1007/978-3-032-07880-3_3}, url = {https://link.springer.com/chapter/10.1007/978-3-032-07880-3_3}, author = {Trung Thach and Kutti R. Vinothkumar and Ramaswamy Subramanian} } @article {163313, title = {CTCF/cohesin-binding sites are susceptible to replication-associated DNA damage and genomic instability in cancer cells}, journal = {iScience}, volume = {29}, year = {2026}, month = {20 February 2026}, pages = {114646}, type = {Research Article}, abstract = {

CTCF/cohesin-binding sites (CBSs) at the chromatin-loop anchors and topologically associating domains are frequently mutated in cancer; however, the underlying molecular mechanisms remain unclear. Here, we investigate whether CTCF and cohesin co-binding on DNA imposes constraints on DNA replication, leading to DNA damage and genomic instability. Our results reveal that CTCF and cohesin remain co-bound to DNA during replication in cancer cells (HeLa). Furthermore, analysis of DNA damage response/repair (DDR) proteins{\textemdash}including MRE11, STN1, γH2AX, and RAD51{\textemdash}showed a high enrichment of these proteins at CBSs, compared with immediate flanking regions. The loss of DDR genes in tumor genomes showed a significant enrichment of somatic mutations at CBSs compared with those tumors with intact DDR genes. Together, we propose that CTCF and cohesin co-binding can impede replication fork progression, leading to DNA damage and DDR activation. However, in cells with defective DDR, these lesions may promote genomic instability at CBSs.

}, keywords = {Bioinformatics, Cancer, Cell biology}, doi = {https://doi.org/10.1016/j.isci.2026.114646}, url = {https://www.sciencedirect.com/science/article/pii/S2589004226000210?via\%3Dihub}, author = {Elangoli Ebrahimkutty Faseela and Dimple Notani and Radhakrishnan Sabarinathan} } @article {163994, title = {Description of Lyriothemis keralensis sp. n. (Odonata: Libellulidae) from the southwestern coast of India}, journal = {International Journal of Odonatology}, volume = {29}, year = {2026}, month = {2026-02-07}, type = {Research Article}, abstract = {

A new species of dragonfly,\ Lyriothemis keralensis\ sp. n. is described from the coastal plains adjoining the Western Ghats of Kerala, southern India, based on a male holotype (IBC-CD161) and a female paratype (IBC-CD310) (type specimens are deposited in the Biodiversity Lab Research Collections, currently held at the National Centre for Biological Sciences, Bengaluru). This taxon was hitherto misidentified as\ L. acigastra\ (Selys, 1878) from which it differs in having leaner abdomen, and differently shaped secondary genitalia and caudal appendages. Information on its biology and ecology are provided.

}, keywords = {anisoptera, conservation, dragonfly, endemic, insect diversity, new species, taxonomy}, url = {https://www.biotaxa.org/ijo/article/view/88280}, author = {DATTAPRASAD SAWANT and A. Vivek Chandran and Renjith Jacob Mathews and Krushnamegh Kunte} } @article {164793, title = {Detection of germline variants in human population chronically exposed to high level natural background radiation in Kerala coast.}, journal = {Genes Environ}, volume = {48}, year = {2026}, month = {2026 Feb 27}, abstract = {

Genetic effects due to long term exposure to low doses of ionizing radiation (LDIR) in humans are not well understood. Human population living in high level natural radiation areas (HLNRAs) of Kerala coast in India are continuously exposed to chronic LDIR emanating from monazite containing beach sand for many generations. The background radiation level in this area varies from \< 1.0 to 45mGy/year. The people residing in HLNRAs sometimes receives background radiation dose which is approximately 10-40 times higher than the people living in adjacent normal level natural radiation areas (NLNRAs). This population provides a unique opportunity to identify, if present, a mutational signature due to chronic low-dose radiation exposure in humans. We have employed whole exome sequencing approach to determine germline mutational changes in the lymphocytes of healthy individuals from HLNRAs (mean background dose: 31.8 {\textpm} 5.4 mGy/year, mean age: 43.0 {\textpm} 5.9 years) and compared them with healthy individuals from NLNRAs (mean background dose: 0.9 {\textpm} 0.2 mGy/year, mean age: 43.0 {\textpm} 11.3 years).

RESULTS: Our results revealed that the overall number of single nucleotide variants (SNVs) and insertions/deletions (indels) were not significantly different in HLNRA (7744 SNVs, 880 indels) and NLNRA (7951 SNVs, 856 indels) groups. A similar number of protein affecting mutations (PAMs) were observed in HLNRA (1925) and NLNRA (2082) individuals. Interestingly, several unique SNVs were identified in both the groups. In HLNRA, unique SNVs were overrepresented in genes involved in important biological pathways such as DNA repair (EXO1, PARP2, DDB1, POLQ, LIG1), epigenetic modification (KDM5D, SETDB2, KMT2B, BRD8, SIRT1), cell cycle progression (CDK14, CCND1) etc. Furthermore, significant predominance of C \> T transitions which were unique to HLNRA group was observed preferentially at CpG dinucleotide regions. Analysis with REVEL and AloFT tools did not show any increase in potentially pathogenic mutations including those involved in carcinogenesis in HLNRA individuals exposed to chronic radiation.

CONCLUSION: This study did not show any significant changes in genetic variants due to long term exposure to LDIR in human population living in HLNRAs of Kerala coast. However, presence of unique SNVs and C \> T transitions in CpG islands of HLNRA individuals indicate the possible role of epigenetic mechanisms i.e. DNA methylation in response to chronic LDIR in this population. This study significantly enhances the current understanding of radiation induced genetic changes and associated cancer risk in human population.

}, keywords = {Chronic radiation, Exome sequencing, High-level natural radiation areas, Human population, Indels, Low dose ionizing radiation (LDIR), Mutation spectrum, Single nucleotide variations (SNVs).}, issn = {1880-7046}, doi = {10.1186/s41021-026-00352-4}, url = {https://link.springer.com/article/10.1186/s41021-026-00352-4}, author = {Jain, Vinay and Saini, Divyalakshmi and Sabarinathan, Radhakrishnan and Das, Birajalaxmi} } @article {164786, title = {Differences in Cellular mechanics and ECM dynamics shape differential development of wing and haltere in Drosophila.}, journal = {Dev Biol}, year = {2026}, month = {2026 Mar 18}, abstract = {

Diverse organ shapes and sizes arise from the complex interplay between cellular properties, mechanical forces, and gene regulation. Drosophila wing- a flat structure and the globular haltere are two homologous flight appendages emerging from a similar group of progenitor cells. The activity of a single Hox transcription factor, Ultrabithorax (Ubx), governs the development of these two distinct organs- wing and haltere with different cell and organ morphologies. Our work reported here on differential development of wing and haltere suggest that the localisation and abundance of actomyosin complexes, apical cell contractility, properties of extracellular matrix, and cell size and shape, which is a result of various cell intrinsic and extrinsic forces, plausibly influence the flat vs. globular geometry of these two organs. Loss of Ubx function led to wing cell-like cellular features in haltere discs, and corresponding changes at the level of adult organs. We also observed that RNAi-mediated downregulation of Atrophin or Pten, in the background of downregulated Expanded (or elevated Yki), gave rise to varying degrees of wing-like homeotic transformations at the cellular as well as adult organ levels. Finally, we employ a minimal vertex model to demonstrate that the observed differences in tissue architecture are physically sufficient to maintain and elaborate early shape differences and mimic flat wing-like or globular haltere-like morphologies. Together, these findings show how genetic and mechanical factors are integrated to generate organ-specific morphologies and provide a framework for understanding the evolution of organ shape.

}, keywords = {3-D tissue shape, cellular mechanical properties, ECM, epithelial tissue mechanics, Haltere, Morphogenesis, organ shape, Ubx, wing.}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2026.03.012}, url = {https://www.sciencedirect.com/science/article/pii/S0012160626000680?via\%3Dihub}, author = {Dilsha, C and Shiju, Salima and Shah, Neel Ajay and Inamdar, Mandar M and Shashidhara, L S} } @article {163320, title = {Disobind: A sequence-based, partner-dependent contact map and interface residue predictor for intrinsically disordered regions.}, journal = {Cell Syst}, volume = {17}, year = {2026}, month = {2026 Jan 21}, pages = {101486}, abstract = {

Intrinsically disordered proteins or regions (IDPs or IDRs) adopt diverse binding modes with different partners, ranging from coupled folding and binding to fuzzy binding and fully disordered binding. Characterizing IDR interfaces is challenging both experimentally and computationally. State-of-the-art tools such as AlphaFold multimer and AlphaFold3 can be used to predict IDR binding sites, although they are less accurate at their benchmarked confidence cutoffs. Here, we developed Disobind, a deep-learning method that predicts inter-protein contact maps and interface residues for an IDR and its partner, given their sequences. It uses sequence embeddings from the ProtT5 protein language model. Disobind outperforms state-of-the-art interface predictors for IDRs. It also outperforms AlphaFold multimer and AlphaFold3 at multiple confidence cutoffs. Combining Disobind and AlphaFold-multimer predictions further improves performance. In contrast to current methods, Disobind considers the context of the binding partner and does not depend on structures and multiple sequence alignments. Its predictions can be used to localize IDRs in large assemblies and characterize IDR-mediated interactions.

}, keywords = {Amino Acid Sequence, Binding Sites, Computational Biology, Deep learning, Humans, Intrinsically disordered proteins, Protein Binding, Protein Folding}, issn = {2405-4720}, doi = {10.1016/j.cels.2025.101486}, url = {https://pubmed.ncbi.nlm.nih.gov/41534519/}, author = {Majila, Kartik and Ullanat, Varun and Viswanath, Shruthi} } @article {164004, title = {EB1 surges promote ciliary outer-segment growth through periodic tubulin influxes into the Drosophila olfactory cilia.}, journal = {J Cell Sci}, volume = {139}, year = {2026}, month = {2026 Jan 15}, abstract = {

Sensory cilia have a complex bipartite architecture containing 9+0 connecting cilia at the inner segment and singlet microtubule-supported highly membranous outer segments essential for receptor display. The mechanisms underlying the formation of such highly branched morphology and its microtubule-rich ciliary cytoskeleton are unclear. Here, we show that individual olfactory cilium inside the large basiconic sensillum grows in episodic steps following several pulsatile influxes of tubulin in developing Drosophila antenna. Transient elevations of the microtubule end-binding protein EB1 precede the tubulin influx events. We also demonstrate that EB1 interacts explicitly with the cargo-binding tail domain of Drosophila KLP68D, a kinesin-2β orthologue. Loss of EB1 in olfactory neurons during the outer segment growth reduces the tubulin influx and affects cilia stability. Finally, we show that the EB1 and tubulin influxes into the distal outer segment of the olfactory cilia require kinesin-2. Altogether, our findings elucidate a role of active EB1 transport in promoting the growth and stability of long-lived metazoan cilia involved in sensory perception.

}, keywords = {Animals, Cilia, Drosophila melanogaster, Drosophila Proteins, Kinesins, Microtubule-Associated Proteins, Microtubules, Olfactory Receptor Neurons, Tubulin}, issn = {1477-9137}, doi = {10.1242/jcs.263625}, url = {https://pubmed.ncbi.nlm.nih.gov/41630694/}, author = {Agarwal, Riddhi Girdhar and Iyer, Saishree Suresh and Barbora, Ayan and Desai, Minita and Gadgil, Yogesh and Jana, Swadhin Chandra and Ray, Krishanu} } @article {163997, title = {EGFR and AR expression and co-expression in Indian triple-negative breast cancer with patient outcome association.}, journal = {Sci Rep}, year = {2026}, month = {2026 Feb 21}, keywords = {AR, Basal TNBC, co-expression of EGFR and AR., EGFR, Molecular profile}, issn = {2045-2322}, doi = {10.1038/s41598-026-40913-9}, url = {https://pubmed.ncbi.nlm.nih.gov/41723216/}, author = {Vaid, Pooja and Puntambekar, Anirudha and Kanse, Pranali and Kadu, Shweta and Agrawal, Piyush and Khatpe, Aditi and Banale, Rituja and Reddy, Ruhi and Kelkar, Devaki A and Hannenhalli, Sridhar and Shashidhara, L S and Koppiker, Chaitanyanand and Kulkarni, Madhura} } @article {164005, title = {EMBO Press co-evolves with molecular ecology and evolutionary biology.}, journal = {EMBO J}, year = {2026}, month = {2026 Feb 18}, issn = {1460-2075}, doi = {10.1038/s44318-026-00723-1}, url = {https://pubmed.ncbi.nlm.nih.gov/41708875/}, author = {Moran, Yehu and Coelho, Susana M and Ettema, Thijs J G and Feschotte, Cedric and Kaltenpoth, Martin and Khila, Abderrahman and Laine, Anna-Liisa and Liow, Lee Hsiang and Petrov, Dmitri and Ramakrishnan, Uma and Sarkies, Peter and Srivastava, Mansi and Voolstra, Christian and Pulverer, Bernd} } @article {164791, title = {Emerging strategies for computational identification of protein-protein interaction hotspots.}, journal = {Curr Opin Struct Biol}, volume = {98}, year = {2026}, month = {2026 Mar 10}, pages = {103241}, abstract = {

A small number of residues at protein-protein interfaces, commonly referred to as hotspots, dominate binding free energy and play a decisive role in stabilizing protein complexes. Identifying these residues is central to understanding the energetic architecture of protein-protein interactions and to developing strategies for therapeutic intervention. Although experimental approaches such as alanine scanning have provided critical insights, they are often impractical for large or dynamic systems. This has positioned computational approaches at the forefront of hotspot analysis. This review highlights recent developments in molecular dynamics simulations and machine-learning-based predictors for hotspot identification, discusses current challenges, and outlines emerging directions in the field. Finally, we suggest that combining these complementary approaches could offer a powerful framework for capturing the dynamic and energetic complexity of protein interfaces, making hotspot predictions more robust and interpretable.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2026.103241}, url = {https://www.sciencedirect.com/science/article/pii/S0959440X26000230?via\%3Dihub}, author = {Pathak, Aditi and Tiwari, Vikas and Sowdhamini, Ramanathan} } @article {166234, title = {Force patterning drives quasistratification and graded tissue-scale spatial order in auditory epithelia}, journal = {Proceedings of the National Academy of Sciences}, volume = {123}, year = {2026}, pages = {e2519341123}, abstract = {

The ordered arrangement of mechanosensory hair cells in vertebrate auditory epithelia relies on mechanical interactions among multiple cell types. Yet, how local mechanical heterogeneity produces tissue-scale organization remains unresolved. Here we combine experiment and theory to show that spatial patterning of junctional contractility links apical surface remodeling to three-dimensional cellular organization and quasi-stratified architecture across the entire extent of the tissue. Building on previous findings on the regulation of force patterning, our results demonstrate how local junctional force heterogeneity generates graded three-dimensional cellular morphology and coordinated cellular movements at the global tissue scale. These findings identify patterned junctional mechanics as a scalable principle for organizing complex epithelia. During development, coordinated cell behaviors drive epithelial morphogenesis toward precise three-dimensional architectures essential for physiological function. How such coordination arises in epithelia composed of multiple cell types remains unclear. Here, we study development of the avian auditory epithelium comprising sensory hair cells (HCs) and nonsensory supporting cells (SCs). Initially, HCs and SCs are arranged into mosaics by Notch{\textendash}Delta signaling. As development proceeds, HCs partially extrude from the epithelium, establish a tenfold gradient in apical surface area across the tissue, and rearrange with SCs to form near-hexagonal order. Using experiments combined with a three-dimensional vertex model, we show that increased contractility at apical junctions between SCs relative to HC{\textendash}SC junctions drives spatial organization both within the epithelial plane and along the apical{\textendash}basal axis. Consistent with experimental findings, our simulation shows systematic differences in HC apical area expansion generate opposing coordinated movements of HCs and SCs, establishing gradients in HC apical surface area and density while maintaining uniform hexagonal order. Together, these results demonstrate that spatial patterning of junctional contractility coordinates cell behavior across both the plane and depth of a mixed epithelium, producing quasi-stratified architecture and tissue-scale three-dimensional order.

}, keywords = {3D vertex model; basilar papilla; development.}, doi = {10.1073/pnas.2519341123}, url = {https://www.pnas.org/doi/abs/10.1073/pnas.2519341123}, author = {Julian Weninger and Anubhav Prakash and Sukanya Raman and Raj k. Ladher and Madan Rao and Karsten Kruse} } @article {164788, title = {Giants of the grass}, journal = {Routledge Handbook of Grasslands}, year = {2026}, month = {March 2026}, abstract = {

Some of the most unique and iconic wildlife assemblages are found in grasslands and savannas across the world. Of these, large herbivores play an especially important role in regulating the structure and functioning of grasslands. This chapter first discusses how large mammalian herbivores influence grassland structure and function and how these effects vary along environmental gradients and with herbivore body size. Next, it discusses the predominant challenges facing conservation of vertebrate wildlife in grasslands, in particular highlighting the role of land-use changes due to agricultural expansion, afforestation for climate mitigation, and population declines due to hunting and climate change.

}, doi = {10.4324/9781003394969-13}, url = {https://www.researchgate.net/publication/402245290_Giants_of_the_grass}, author = {Mayank Kohli and Mahesh Sankaran} } @article {164008, title = {GRAYU: graph-based database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases}, journal = {frontiers}, volume = {16}, year = {2026}, month = {22 January 2026}, abstract = {

The translation of India{\textquoteright}s extensive traditional knowledge on indigenous medicinal plants into modern therapeutic solutions is contingent upon a systematic framework. While traditional Indian medicine offers a rich source of therapeutic leads, this knowledge is often not structured for modern computational analysis, creating a barrier to systematic drug discovery.
To this end, we present GRAYU, a curated and comprehensive online database that integrates data across multiple categories, connecting 1,039 traditional formulations to 12,743 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases.\ 
GRAYU provides insights into 1,370,257 plant-phytochemical, 116,531 plant-disease, 2,389 plant-formulation, and 4,087 formulation-disease associations. We show potential applications on phytochemical analogs, sustainable plant substitution, and disease-network analysis, highlighting the potential of integrative graphs to decode shared molecular signatures and therapeutic networks across traditional Ayurvedic formulations.
GRAYU represents a user-friendly resource for researchers to investigate complex bio-associations and formulate novel therapeutic hypotheses, with insights from traditional Indian medicine. GRAYU organises reported associations and computational relationships and can hint at mechanistic causality or biological activity; however, all outputs require contextual interpretation and further experimental validation.

}, keywords = {Data integration, Drug repurposing, Endangered plants, Knowledge graph, Network pharmacology, Traditional foods}, doi = {https://doi.org/10.3389/fphar.2025.1727224}, author = {Sarthak Joshi and Aditi Pathak and Dheemanth Reddy Regati and Revathy Menon and Deepthi S. Ajith and Aditya Sheshadri and Neerja Viswanathan and Poulomi Ray and Vimarishi Koul and Pratishruti Panda and Shriya Anand Bhambore and Shailya Verma and Ananya Sinha and K. Mohamed Shafi and Murugavel Pavalam and Ramanathan Sowdhamini} } @article {165836, title = {A growing role for ER-Ca2+ release and store-operated Ca2+ entry in neuronal physiology and pathophysiology}, journal = {Current Opinion in Neurobiology}, volume = {98}, year = {2026}, pages = {103195}, abstract = {

Among its many functions, the endoplasmic reticulum (ER) in eukaryotes serves as a store for intracellular Ca2+. In metazoan cells, there are two classes of ER membrane localized channels that release intracellular Ca2+ in response to external signals. ER-Ca2+ release is followed by extracellular Ca2+ entry through a process called store-operated Ca2+ entry (SOCE), essential for cellular Ca2+ signaling and homeostasis. Recent findings suggest that neuronal SOCE differs based on the nature of ER-Ca2+ release channels activated and the architecture of the ER across neuronal compartments. These properties determine the amplitude and time of ER-Ca2+ release and SOCE, which in turn determine activation of downstream effector molecules. The importance of these findings is discussed in the context of normal physiology and neurodegenerative conditions. Drugs targeting regulators of ER-Ca2+ release and SOCE show promise in terms of reverting symptoms of neurodegenerative conditions such as Alzheimers{\textquoteright} disease.

}, issn = {0959-4388}, doi = {https://doi.org/10.1016/j.conb.2026.103195}, url = {https://www.sciencedirect.com/science/article/pii/S0959438826000310}, author = {Gaiti Hasan} } @article {166232, title = {Histone variant H2A.X represses deposition of active H3K4me3 marks and restricts H2A.W incorporation}, journal = {Nucleic Acids Research}, volume = {54}, year = {2026}, month = {05}, pages = {gkag476}, abstract = {

Histone variant H2A.X is a well-conserved histone that plays crucial roles in mediating DNA damage response across eukaryotes. Although H2A.X expresses and decorates gene bodies of actively expressed genes even without stress, it is not known if H2A.X has functions beyond DNA damage repair. Using genetic, high-throughput genomics, and molecular approaches, we identified a previously unappreciated role of H2A.X in regulating development-associated genes. Using custom-made antibodies specific to the rice H2A.X variant, we show that it repressed the deposition of active H3K4me3 marks over gene bodies and transposable elements (TEs), specifically regulating root development, photosynthesis, and pigmentation-related genes, as seen by the impairment of these processes in rice h2a.x knockout (ko) plants. H2A.X also repressed global deposition of repressive mark H3K9me2 by restricting the activity of H2A variant H2A.W. In agreement with this, there was a genome-wide relocalization of H2A.W to TEs and a few genes in ko plants. H2A.X-overexpressing plants exhibited stress phenotypes, including increased anthocyanin levels, mimicking the transcriptome of DNA-damaged wild-type (WT) plants. The transcriptome of knockdown (kd) lines of facilitates chromatin transcription (FACT) complex, a known chaperone of H2A.X, was largely similar to that of h2a.x ko plants, suggesting that the development-associated functions of FACT are at least partially due to H2A.X. These results suggest a specific role of H2A.X in regulating competing histone marks, a function that might also be conserved across plants.

}, issn = {1362-4962}, doi = {10.1093/nar/gkag476}, url = {https://doi.org/10.1093/nar/gkag476}, author = {Madhu, Aravind and Gandhivel, Vivek Hari-Sundar and Raju, Steffi and Dey, Riju and Shivaprasad, Padubidri V} } @article {161132, title = {Immunofluorescence Staining and Microscopic Imaging of Plant Nuclei for Epigenetic Modifications.}, journal = {Methods Mol Biol}, volume = {2988}, year = {2026}, month = {2026}, pages = {83-92}, abstract = {

Histone posttranslational modifications (PTMs) and DNA methylation are the predominant epigenetic modifications on the chromatin that regulate gene expression. These modifications can be spatially resolved using microscopic examination of the nuclei with the help of commercially available antibodies. Here, we describe a detailed method to obtain intact nuclei from plant tissues and reproducibly immunostain the nuclei for specific chromatin marks and microscopic examination. This method can be readily extended to multiple plant species as the antibodies are raised against conserved epigenetic marks.

}, keywords = {Cell Nucleus, Chromatin, DNA Methylation, Epigenesis, Genetic, Epigenomics, Fluorescent Antibody Technique, Histones, Microscopy, Fluorescence, Plants, Protein Processing, Post-Translational}, issn = {1940-6029}, doi = {10.1007/978-1-0716-4981-7_8}, author = {Gandhivel, Vivek Hari-Sundar and Raju, Steffi and Shivaprasad, P V} } @article {164794, title = {Integrative modeling with AlphaFold.}, journal = {Curr Opin Struct Biol}, volume = {98}, year = {2026}, month = {2026 Mar 10}, pages = {103239}, abstract = {

Macromolecular assemblies underpin essential cellular processes, yet their structural characterization remains challenging. Integrative modeling provides an approach for determining structures of macromolecular assemblies, combining diverse experimental data with physical principles, the statistics of previous structures, and prior models. There is a growing interest in leveraging the implicit structural knowledge learned by artificial intelligence-based structure-prediction methods such as AlphaFold (AF), for integrative modeling. Here, we discuss recent methods that combine AF with experimental data for integrative modeling in four ways: validating AF-based ensembles with experimental data; combining structural priors from AF with experimental data; fine-tuning AF with experimental data; and incorporating experimental data at inference time. We also outline key challenges in integrative structure determination using AF.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2026.103239}, url = {https://www.sciencedirect.com/science/article/pii/S0959440X26000217?via\%3Dihub}, author = {Majila, Kartik and Golatkar, Omkar and Viswanath, Shruthi} } @article {163321, title = {Intraspecific Trait Variation Predicts Species Distributions and Niche Occupancy of Seedlings in a Tropical Wet Forest}, journal = {bioTropica}, year = {2026}, month = {29 December 2025}, type = {Research Article}, abstract = {

Functional traits enable comparison among species to elucidate general patterns and processes. While most work on trait-mediated ecology employs variation among species, recent studies show that intraspecific trait variation (ITV) can significantly affect community dynamics. We examined the extent of ITV in seedlings of woody plants and its influence on abundance patterns and niche parameters in a tropical wet forest. Using 14 species that had at least 5 individuals across 150 2 {\texttimes} 2-m plots arrayed across a gradient of light and water availability, we estimated species{\textquoteright} niche properties (breadth and position) and abundance. We measured eight functional traits corresponding to morphological and allocational features of leaves, stems and roots, from which we estimated ITV and functional position of species. We used variance partitioning to determine the relative extent of trait variation at different ecological levels and used linear models to assess the relationship between ITV, abundance, and niche properties. ITV accounted for 30{\textendash}100\% of trait variation. Only leaf dry matter content showed a significant link between abundance and ITV via niche breadth along light and soil moisture gradients and via niche position along soil organic carbon gradients. While ITV of no other trait correlated with abundance, root, stem, and leaf mass fractions showed significant relations with niche breadth. Overall, ITV in seedlings was substantial and shaped niche properties, but this did not consistently translate to patterns in abundance. Future work should link ITV to species{\textquoteright} performance to better comprehend the mechanisms underlying plant community dynamics.

}, doi = { https://doi.org/10.1111/btp.70150Digital Object Identifier (DOI)}, url = {https://onlinelibrary.wiley.com/doi/10.1111/btp.70150}, author = {Vikhyath Premugh and Rajaditya Das and Ashish Nambiar and Meghna Krishnadas} } @article {163311, title = {Investigating Enzyme-Substrate Interactions in the Assembly of K48/K63 Heterotypic Ubiquitin Chains.}, journal = {Biochemistry}, year = {2026}, month = {2026 Jan 26}, abstract = {

Ubiquitination, a post-translational modification, regulates numerous cellular processes by attaching ubiquitin molecules to the target proteins, thereby altering their cellular levels and functions. A central aspect of ubiquitin-mediated signaling is the formation of different types of polyubiquitin (polyUb) chains, which can be either homotypic or heterotypic, generating a variety of cellular signals that activate distinct downstream pathways. Homotypic chains are linked via the same lysine on each molecule, whereas heterotypic chains are conjugated via multiple lysines. The synthesis of these diverse polyubiquitin chains is driven by interactions between substrate-conjugated ubiquitin molecules, ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). However, the molecular details of these interactions and how they govern the synthesis of different homotypic and heterotypic chains remain poorly understood. The E2 enzyme E2-25K preferentially extends K48-linked polyubiquitin chains on K63-linked template polyubiquitin chains, creating branched K48/K63 chains. In this study, we investigated the role of dynamic interactions between E2-25K and the K63-linked diubiquitin substrate to assess the molecular mechanism of branched-chain assembly. Our data reveal that E2-25K shows no preference for binding to the proximal or distal ubiquitin of a template chain. However, binding to the distal unit activates the complex; binding to the proximal unit does not. This study highlights the critical role of stereospecificity in enzyme/substrate interactions for branched ubiquitin chain synthesis and provides insights into the mechanisms of ubiquitin signaling.

}, keywords = {Conformation, Genetics, Nuclear magnetic resonance spectroscopy, Peptides and proteins, Titration}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5c00709}, url = {https://pubs.acs.org/doi/10.1021/acs.biochem.5c00709}, author = {Singh, Gajendra and Negi, Hitendra and Ravichandran, Aravind and Yadav, Shalu and Das, Ranabir} } @article {164006, title = {The lipid language of tuberculosis: surface molecules in host interaction and drug resistance.}, journal = {mBio}, year = {2026}, month = {2026 Feb 02}, pages = {e0395925}, abstract = {

(), the causative agent of tuberculosis (TB), is a uniquely successful pathogen due in large part to its complex lipid-rich cell envelope. Comprising nearly 40\% of its dry weight, lipids-such as mycolic acids, phthiocerol dimycocerosates (PDIM), trehalose dimycolate (TDM), and sulfolipids (SLs)-play crucial roles in infection, immune evasion, intracellular persistence, granuloma formation, transmission, and drug resistance. These lipids modulate host-pathogen interactions by altering host membrane biophysics, hijacking phagosome maturation, and interfering with host immune pathways, including autophagy and inflammatory signaling. Upon inhalation, surface lipids inhibit pulmonary surfactant function and mask pathogen-associated molecular patterns, facilitating uptake by permissive macrophage subsets. Intracellularly, lipoglycans like mannose-capped lipoarabinomannan block phagolysosome fusion, while PDIM and TDM promote phagosomal escape and subversion of vesicular trafficking. Lipid-mediated modulation of autophagy pathways further enhances bacterial survival within host cells. In addition to shaping host immune responses, lipids orchestrate granuloma development and promote pathological features such as foam cell formation and caseation, which are central to transmission. Specifically, phenolic glycolipids and SLs stimulate neuronal pathways, triggering cough, thereby facilitating aerosol spread. Finally, the lipid-rich envelope acts as a formidable barrier to antibiotics, with resistance partly driven by the altered lipid composition and architecture in multidrug-resistant strains. Targeting lipid biosynthesis and transport pathways offers promising avenues for novel anti-TB therapies. This review highlights the multifaceted roles of lipids at the host-pathogen interface, recent technical advances enabling these insights, and emerging challenges in translating lipid biology into improved TB control.

}, keywords = {cell wall, Host-Pathogen Interactions, Mtb lipids, multidrug resistance, Mycobacterium tuberculosis, pathogenesis.}, issn = {2150-7511}, doi = {10.1128/mbio.03959-25}, url = {https://pubmed.ncbi.nlm.nih.gov/41627032/}, author = {Radhakrishnan, Sandhya Krishnan and Sundaramurthy, Varadharajan} } @article {166233, title = {Minimal Sample, Maximum Insight: DNA Metabarcoding Uncovers the Diet of Endangered Dholes in Central India}, journal = {Environmental DNA}, volume = {8}, year = {2026}, pages = {e70306}, abstract = {

ABSTRACT Understanding the dietary ecology of endangered carnivores is critical for their conservation and management, as it elucidates their interaction with prey, other co-occurring carnivores, and humans. We used DNA metabarcoding to examine the seasonal and spatial variation in the diet of dholes (Cuon alpinus) in Tadoba Andhari Tiger Reserve, a key stronghold for the species in central India. We evaluated a simpler non-invasive fecal sample collection method and optimized a novel blocking oligonucleotide to suppress host DNA amplification. Our results revealed that pinches of scat in lysis buffer, coupled with N-spacer-tagged primers for amplifying diet DNA, significantly improved prey detection, sequencing efficiency, and reduced host contamination compared to traditional whole-scat-in-silica methods. Across 169 genetically confirmed dhole scats collected over two different seasons, we identified 15 vertebrate prey species. Dhole diet was dominated by wild ungulates, especially chital (Axis axis) and sambar (Rusa unicolor), with negligible consumption of domestic species. However, we observed strong seasonal and spatial variation; monsoon diet was diverse with greater variability, while winter diet was more consistent and dominated by large-bodied prey. Core zone exhibited wider dietary profiles than buffer areas that included mixed use landscapes. These findings suggest that wild prey availability, habitat quality, and seasonal foraging constraints shape dhole dietary patterns. Our study underscores the value of improved sampling and sequencing strategies for carnivore dietary studies and highlights the importance of sustaining wild prey populations to ensure the long-term persistence of dholes in multi-use landscapes.

}, keywords = {Cuon alpinus, feeding ecology, N-spacers, non-invasive samples, single amplicon sequencing, Tadoba Andhari Tiger Reserve}, doi = {https://doi.org/10.1002/edn3.70306}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/edn3.70306}, author = {Tyagi, Abhinav and M., Alex and Hushangabadkar, Prajakta and Kale, Nandkishor and Ramgaokar, Jitendra and Ramakrishnan, Uma} } @article {164007, title = {The multifaceted phosphatidylinositol 5 phosphate 4-kinase proteins: molecular properties and biological functions.}, journal = {Biochim Biophys Acta Mol Cell Biol Lipids}, volume = {1871}, year = {2026}, month = {2026 Jan}, pages = {159698}, abstract = {

Phosphoinositides are regulators of key cell biological processes such as plasma membrane function, vesicular transport, cytoskeletal and nuclear organization. In turn, their levels are tightly controlled by the function of lipid kinases and phosphatases that modify specific hydroxyl groups on the inositol ring. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is one such lipid kinase. Although initially discovered as an enzyme that phosphorylates the 4th hydroxyl on the inositol ring of phosphatidylinositol 5 phosphate (PI5P) with exquisite specificity, it has recently emerged that PIP4K may also work on other substrates. Interestingly, recent studies have also proposed functions for this enzyme that do not require its catalytic activity. Although most elements of phosphoinositide signalling are conserved across all eukaryota, a limited number of phosphoinositide kinases and phosphatases including PIP4K seem to be a unique feature of the genomes of organisms that exist in a multicellular state but not unicellular eukaryotes. Genetic studies in model organisms implicate PIP4K function in key processes such as hormone regulated metabolic control as well as cell division and growth. Consequently, PIP4K function has important biomedical implications in the context of cancer, metabolic syndrome and autoimmune disorders. In this review, we analyze emerging findings on PIP4K function and reflect on the biochemical raison d{\textquoteright}{\^e}tre of how this protein regulates cell physiology in metazoans.

}, keywords = {Animals, Humans, Phosphatidylinositol Phosphates, Phosphotransferases (Alcohol Group Acceptor), Signal Transduction}, issn = {1879-2618}, doi = {10.1016/j.bbalip.2025.159698}, url = {https://pubmed.ncbi.nlm.nih.gov/41130585/}, author = {Krishnan, Harini and Venugopal, Aishwarya and Alex, Preethi and Raghu, Padinjat} } @article {166221, title = {NELFA-mediated pausing restrains YAP transcription and context-dependent outcomes in breast cancer}, journal = {Frontiers in Oncology}, volume = {Volume 16 - 2026}, year = {2026}, abstract = {

IntroductionThe Hippo pathway effector YAP signaling is frequently dysregulated in cancer, promoting transcriptional programs linked to tumor progression. However, how general transcriptional control mechanisms intersect with YAP activity remains unclear.MethodsWe investigated the role of NELFA, a component of promoter-proximal pausing (PPP), using genetic perturbation in HEK293T cells and MDA-MB-231. Transcriptomic profiling and analysis of three independent breast cancer cohorts were performed to assess clinical relevance.ResultsNELFA depletion resulted in selective amplification of YAP-dependent transcription in HEK293T and MDA-MB-231. Gene expression analyses showed enrichment of YAP targets alongside epithelial{\textendash}mesenchymal transition and TGF-β signaling{\textendash}associated programs. Clinically, low NELFA expression correlated with poorer disease-free survival in YAP-high tumors, specifically in triple-negative breast cancer.DiscussionThese findings identify PPP as a conserved regulatory layer modulating YAP-driven oncogenic transcription. Loss of NELFA may enhance oncogenic transcriptional programs specifically in TNBC, highlighting its potential relevance as a context-dependent biomarker in aggressive breast cancer subtypes.

}, keywords = {NELFA; TNBC; breast cancer; promoter proximal pausing (PPP) complex; yes-associatedprotein-1 (YAP).}, issn = {2234-943X}, doi = {10.3389/fonc.2026.1808415}, url = {https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1808415}, author = {Vasave, Bhavesh S. and Atreya, Aadya A. and Kulkarni, Rishabh D. and Nagarkar, Sanket S. and Salvi, Khushi R. and Koppiker, C. B. and Shashidhara, L. S. and Kulkarni, Madhura D.} } @article {164000, title = {Odor tracking in insects: a multisensory behavior.}, journal = {J Exp Biol}, volume = {229}, year = {2026}, month = {2026 Feb 15}, abstract = {

Insects rely on sophisticated odor-tracking mechanisms to locate mates and food sources, or follow conspecific trails, in both two (e.g. substrate-based tracking by ants and termites) and three (e.g. airborne pheromone plume tracking by flying insects) dimensions. These behaviors rely on the integration of multisensory information and understanding them requires us to draw upon principles from odor transport physics, odor chemistry and sensory ecology. Airborne odor plumes are typically heterogeneous and turbulent, delivering chemical cues in intermittent bursts, while ground-based odor trails are more stable and localized. Hence, insects employ fundamentally distinct strategies to navigate these environments, shaped by the physical and chemical properties of the odorants. Insect odor-tracking behavior is mediated by an array of sensory modalities, including chemosensory, visual, mechanosensory and thermal inputs. Experimental approaches in both laboratory and field settings have revealed how insects integrate these cues to successfully identify odor sources under complex environmental conditions. Comparative studies, such as those examining diurnal versus nocturnal tracking, highlight how sensory prioritization shifts with ecological context, revealing adaptive neural integration mechanisms. This article reviews the behavioral strategies insects use for odor tracking in air and on the ground, focusing on the role of multisensory integration and the vulnerability of these behaviors to sensory noise. Emerging research on environmental disruptions, such as artificial light at night and air pollution, highlights the ecological threats to odor-mediated behaviors. By synthesizing insights from diverse insect taxa, we examine how sensory noise and anthropogenic change can impair essential behaviors such as foraging and mating.

}, keywords = {Animals, Behavior, Animal, Cues, Insecta, Odorants, Smell}, issn = {1477-9145}, doi = {10.1242/jeb.250945}, url = {https://pubmed.ncbi.nlm.nih.gov/41668668/}, author = {Soman, Shuchita and Ramaswamy, Sree Subha and Sane, Sanjay P} } @article {164800, title = {Partial recovery of large seed arrival following ecological restoration in fragmented tropical rainforests}, journal = {Nordic Society Oikos}, year = {2026}, month = {24 February 2026}, abstract = {

Forest restoration success depends crucially on the reinitiation of ecological processes such as seed arrival that drive natural regeneration. We know little about whether, by increasing and diversifying local seed sources to alleviate seed limitation, and attracting animal frugivores to alleviate dispersal limitation, restoration could shift seed arrival rates and species composition in the direction of mature rainforests, particularly for large-seeded species in degraded fragments. We tested this by examining seed arrival over a year in 189 1-m2\ seed fall traps within 63 seed trapping stations across sites ecologically restored (through maximum diversity mixed-native species planting 13{\textendash}21 years ago) and those left unrestored within degraded rainforests fragments, and in mature {\textquoteleft}benchmark{\textquoteright} rainforests, in India{\textquoteright}s Western Ghats. We found that overall, large-seeded species arrival rates in restored sites was comparable with benchmark, and was higher than unrestored sites. Seeds arriving through dispersal (from fruiting trees absent in the overstory) also showed a recovery towards benchmark levels, but were dominated by alien species abundant in the matrix habitat. Restoration also had no effect on species richness and composition of all arriving seeds, with restored sites closely resembling unrestored sites and remaining distinct from benchmark sites. Further, restoration did not alleviate the effect of fragment isolation on large seed arrival rates, which declined with distance from benchmark forests similarly in restored and unrestored sites. Our results suggest that restoration can increase local availability and dispersal of large seeds, and highlights the value of diverse native species restoration plantings within degraded forests and promoting their use instead of alien tree species in the surrounding matrix. However, our findings also show that recovery of natural regeneration can remain slow or uncertain in restored forest fragments, and underscore the need for sustained monitoring and evaluation of restoration over multiple decades.

}, doi = {10.1002/oik.11945}, url = {https://nsojournals.onlinelibrary.wiley.com/doi/full/10.1002/oik.11945}, author = {Aparna Krishnan and Jyotsna Nag and S. Arun and Divya Mudappa and T. R. Shankar Raman and Mahesh Sankaran and Anand M. Osuri} } @article {163319, title = {Physico-chemical regulation of bacterial growth success under 3D confinement.}, journal = {Soft Matter}, year = {2026}, month = {2026 Jan 22}, abstract = {

How environmental factors influence bacterial growth remains an extensively pursued, yet perennially challenging question. Most natural bacterial habitats are complex 3D spaces, featuring disordered spatial architectures, heterogeneous nutrient availability, and broad temperature ranges. However, state-of-the-art knowledge on bacterial growth almost entirely derives from conventional experimental platforms - liquid culture and 2D flat plates - which offer limited capacity to recapitulate the diverse physico-chemical aspects intrinsic to physiological niches. Consequently, we do not fully understand how manifold environmental variables act in concert to influence growth dynamics. Here, we report the first-such interrogation of bacterial growth success under 3D confinement across combinatorial physico-chemical regimes. We accomplish this by engineering mechanically tunable viscoelastic 3D porous media, multiplexed with three distinct nutrient compositions and five different growth temperatures. Across this parameter space, we discover regimes of either confinement-driven or temperature-driven growth success, as well as nutrient composition-dependent modulation of these effects. Our work identifies a tripartite regulatory framework that captures the inter-linked effects of three generic environmental variables - mechanical constraints, nutrient availability, and temperature - on growth under 3D confinement, supported by direct experimental evidence. Together, our findings establish how environmental factors influence growth across physico-chemically complex 3D milieus.

}, issn = {1744-6848}, doi = {10.1039/d5sm01082a}, url = {https://pubmed.ncbi.nlm.nih.gov/41568648/}, author = {Bagade, Nikita and Sreepadmanabh, M and Ganesan, Gokulnath and Bhattacharjee, Tapomoy} } @inbook {163314, title = {Recent Methods from Statistical Inference for Integrative Structural Modeling}, booktitle = {Springer Handbook of Chem- and Bioinformatics }, year = {2026}, pages = {1075{\textendash}1103}, publisher = {Springer, Cham}, organization = {Springer, Cham}, abstract = {
Integrative modeling of macromolecular assemblies allows for structural characterization of large assemblies that are recalcitrant to direct experimental observation. A Bayesian inference approach facilitates combining data from complementary experiments along with physical principles, statistics of known structures, and prior models, for structure determination. Here, we review recent methods for integrative modeling based on statistical inference and machine learning. These methods improve over the current state-of-the-art by improving data collection, optimizing coarse-grained model representations, making scoring functions more accurate, sampling more efficient, and model analysis more rigorous. We also discuss three new frontiers in integrative modeling: incorporating recent deep learning-based methods, integrative modeling with in situ data, and metamodeling.
}, keywords = {AlphaFold, Crosslinking coupled with mass spectrometry, Deep learning, Dynamical Integrative Structure Modeling, Electron cryo-microscopy, Electron cryo-tomography, Integrative structure modeling, Whole-cell modeling}, isbn = {Print ISBN 978-3-031-81727-4}, issn = {Online ISBN 978-3-031-81728-1}, doi = {https://doi.org/10.1007/978-3-031-81728-1_47}, url = {https://link.springer.com/chapter/10.1007/978-3-031-81728-1_47}, author = {Shreyas Arvindekar and Kartik Majila and Shruthi Viswanath} } @article {164787, title = {Responses of African Savanna Trees to Large Herbivore Extinction and Rewilding.}, journal = {Ecol Lett}, volume = {29}, year = {2026}, month = {2026 Mar}, pages = {e70360}, abstract = {

The global decline or extinction of large mammals over the last 50,000 years has caused sweeping changes in the ecosystems they once inhabited. Trophic rewilding holds promise for returning lost ecological function and restoring processes that support ecosystem resilience, but there remains considerable uncertainty surrounding the efficacy of rewilding. To address this uncertainty, we experimentally excluded a diverse African savanna mammal community from replicated plots for 18 years to simulate extinction. Herbivore exclusion caused a rapid increase in tree cover, which was underlain by shifts in community composition and increases in canopy area, growth rate and density. We then removed the exclosure fences, simulating rewilding. Reintroducing herbivores rapidly reduced tree cover and largely reversed individual phenotypic shifts, but tree density remained elevated despite increased mortality rates after reintroduction. Our results suggest that even short-term extirpation can cause complex shifts in vegetation communities, some of which may be resistant to rewilding.

}, keywords = {Africa, Animals, Conservation of Natural Resources, Extinction, Biological, Grassland, Herbivory, Mammals, Trees}, issn = {1461-0248}, doi = {10.1111/ele.70360}, url = {https://onlinelibrary.wiley.com/doi/10.1111/ele.70360}, author = {Coverdale, Tyler C and Sankaran, Mahesh and Davies, Andrew B and Ratnam, Jayashree and Wigley, Benjamin J and Augustine, David J} } @article {164795, title = {Restoration goals: Insights from antiquity and dynamics of forest{\textendash}savanna mosaics in Central India during the Holocene}, journal = {ResearchGate}, year = {2026}, month = {24 March 2026}, abstract = {

Forest{\textendash}savanna mosaics are important for biodiversity, but the savannas in these mosaics are often considered degraded forests due to low tree cover, and are thus targeted for tree planting. Yet, these mosaics may be naturally bistable systems, wherein disturbance regimes such as fire and herbivory create alternative stable states of forest and savanna. Globally, forest{\textendash}savanna mosaics have been present from pre-historic times and map to regions with high biodiversity today. Here, we conduct a meta-analysis of paleo-ecological studies in Central India{\textemdash}a highly biodiverse forest{\textendash}savanna mosaic landscape threatened by tree plantations today{\textemdash}to understand the spatiotemporal antiquity and dynamics of the mosaics across this region. We find that alternate states of low and high tree cover have been present in Central India since the early Holocene and that the tree cover is explained by the interaction of mean annual precipitation (MAP) and the disturbance regime of fire. We find no statistical evidence for bimodality or hysteresis{\textemdash}conditions that are required for alternative stable states{\textemdash}although patterns suggestive of alternative stable states are present. Further, in contradiction to the hypothesis of high and low tree cover states being stable, this system transitions between alternate states of high and low tree cover at time periods ranging from ~40 to 220 years. Switching back and forth between alternate states is significantly more frequent in sites with higher richness of fire-resistant tree taxa. Our historical data thus lend support to the idea that low tree cover regimes have been created or maintained through interactions between climatic conditions and disturbance regimes such as fire, and that tree cover can increase when either of these factors changes. The study further suggests that restoration should focus on maintaining the ability to switch between low and high tree cover rather than increasing tree cover in Central India.

}, doi = {10.1002/eap.70188 }, url = {https://esajournals.onlinelibrary.wiley.com/doi/abs/10.1002/eap.70188}, author = {Meghna Agarwala and Krishna Pavan Komanduri and Mohammad Firoz Quamar and Charuta Kulkarni and Jayashree Ratnam} } @article {163993, title = {Selective Sequestration of Cardenolides Shapes Chemical Defense in an Aposematic Butterfly.}, journal = {J Chem Ecol}, volume = {52}, year = {2026}, month = {2026 Feb 19}, pages = {20}, abstract = {

Aposematic insects often sequester plant toxins as chemical defenses, but the extent to which they selectively retain or eliminate specific compounds remains poorly understood. We investigated toxin sequestration in Danaus chrysippus, a chemically defended butterfly that feeds on the cardenolide-rich milkweed Calotropis gigantea. Using untargeted metabolomics, targeted cardenolide quantification, and Na$^{+}$/K$^{+}$-ATPase inhibition assays, we tested whether sequestration is compound-selective and compared the biochemical potency of plant and insect samples. Untargeted profiles showed that caterpillars and adults converge on an insect-specific metabolome, while frass retains a plant-like chemical signature. Targeted analyses showed consistent retention of four cardenolides (calotropagenin, coroglaucigenin, uzarigenin, frugoside) across developmental stages, complete exclusion of uscharin, and progressive loss of calotropin and calotoxin across metamorphosis. Enzyme assays revealed strong differences among sample types: frass showed the strongest inhibition (~ 5-fold weaker than the ouabain standard), adults were intermediate (~ 18-19-fold), and leaves and caterpillars were the weakest (~ 45-58-fold). These potency differences mirrored qualitative composition, frass contained the full set of detected cardenolides, whereas adults retained only a reduced subset. While porcine Na$^{+}$/K$^{+}$-ATPase assays quantify biochemical activity rather than predator deterrence, our results demonstrate clear compound-level selectivity and suggest that physiological filtering shapes the repertoire of plant toxins available for defense in aposematic insects.

}, keywords = {Animals, Asclepias, Butterflies, Cardenolides, Larva, Plant Leaves, Sodium-Potassium-Exchanging ATPase}, issn = {1573-1561}, doi = {10.1007/s10886-026-01695-6}, url = {https://link.springer.com/article/10.1007/s10886-026-01695-6}, author = {Mushtaq, Saleem and Kunte, Krushnamegh and Venkatesan, Radhika} } @article {163999, title = {Sensory biology in a changing world: multisensory systems and interdisciplinary collaboration.}, journal = {J Exp Biol}, volume = {229}, year = {2026}, month = {2026 Feb 15}, abstract = {

Animals have evolved multiple sensory systems that can acquire environmental information guiding their behaviour, allowing them to adapt physiological parameters to current conditions. However, over the past century, anthropogenic changes have increasingly made information on environmental conditions less reliable, by introducing novel elements (such as synthetic chemicals or artificial light), by altering environmental parameters such as temperature, and by introducing fluctuations. Animals using multimodal information perceived through multiple senses may be more resilient to changes, as they can adjust their sensory strategy, giving more weight to information channels that are less disturbed than others. In this Commentary, we propose that to better understand how animals are affected by disturbed access to sensory information that is caused by anthropogenic influences, sensory biologists need to study all developmental stages of a wide range of species, and include entire ecosystems in their thinking. Comparative, interdisciplinary studies will be increasingly important if we are to understand and mitigate the sensory consequences of anthropogenic changes for animals.

}, keywords = {Animals, Ecosystem, Interdisciplinary Communication, Sensation}, issn = {1477-9145}, doi = {10.1242/jeb.251786}, url = {https://pubmed.ncbi.nlm.nih.gov/41668653/}, author = {Kelber, Almut and Gilmour, Kathleen M and Sane, Sanjay P} } @article {164799, title = {Six new species of Calicnemia Strand, 1926 and one new species of Coeliccia Kirby, 1890 (Odonata: Zygoptera: Platycnemididae) from northeastern India}, volume = {5760}, year = {2026}, month = {2026-02-25}, chapter = {401-449}, abstract = {

We erect six new species of the genus Calicnemia Strand, 1926, namely, Ca. ardena sp. nov., Ca. arunachala sp. nov., Ca. flavovittata sp. nov., Ca. mimumkoa sp. nov., Ca. naga sp. nov. and Ca. rubromacula sp. nov.; and one new species of Coeliccia Kirby, 1890, Co. magna sp. nov., from northeastern India. The new Calicnemia spp. are distinguished based on the structure of the genital ligula, colouration patterns of the thorax and abdomen, and the shape of caudal appendages. Based on the morphology of the genital ligula, we propose a third species group within Calicnemia, in addition to the two previously recognised species groups. This new species group accommodates Ca. ardena sp. nov. and Ca. rubromacula sp. nov., which possess short, bifurcated genital filaments that do not align with the diagnostic characteristics of the existing species groups. Additionally, Ca. erythromelas (Selys, 1891) previously reported from India is shown to be misidentified, and the Indian material is identified as Ca. naga sp. nov. Updated identification keys for all known Calicnemia males are provided, along with detailed illustrations of diagnostic features. Coeliccia magna sp. nov., erected from Arunachal Pradesh, is distinguished from congeners by its larger body size, complete blue antehumeral stripes, and distinct male and female morphological features. We further provide lateral thoracic illustrations of Coeliccia spp.

}, doi = {10.11646/zootaxa.5760.4.1}, url = {https://www.mapress.com/zt/article/view/zootaxa.5760.4.1}, author = {DATTAPRASAD SAWANT and SHANTANU JOSHI and UJWALA PAWAR and FAHIM KHAN and VIRAJ NAWGE and Krushnamegh Kunte} } @article {166224, title = {Strengthening India{\textquoteright}s field biology infrastructure: establishing a network of field stations}, journal = {Journal of Experimental Biology}, volume = {229}, year = {2026}, month = {05}, pages = {jeb252222}, abstract = {

India harbours diverse ecosystems {\textendash} ranging from alpine meadows to coral reefs, grasslands to wetlands, deserts to tropical rainforest {\textendash} each supporting unique flora and fauna. This exceptional diversity is compressed into a relatively small geographical area and coexists with the world{\textquoteright}s largest human population amidst rapid infrastructural development, leading to significant changes in India{\textquoteright}s habitats and biodiversity. There is an urgent need for long-term field-based research to document and understand the biogeography, behaviour comparative physiology and ecology of organisms in these ecosystems, especially in the context of climate change. This would advance fundamental biological science and generate the conceptual and empirical evidence required for effective conservation policy. However, field research depends critically on clearly defined long-term vision and access to well-equipped field stations. Many existing Indian field stations are institution specific and provide rudimentary facilities, often functioning from rented premises and lacking dedicated research infrastructure, laboratories, reliable power supply, connectivity and facilities for systematic data collection and long-term monitoring. This Perspective aims to highlight scientific opportunities offered by India{\textquoteright}s diverse ecosystems, identify major infrastructural lacunae and bottlenecks that limit these opportunities, and outline ways to address these challenges. We argue for the establishment of a country-wide network of modern field stations to support sustained long-term field-based studies through stable funding and multi-institutional cooperation. These field stations are envisaged as permanent research and monitoring centres located within key ecological landscapes. Beyond research, such stations can serve as hubs for training, capacity building, public engagement and knowledge integration, thereby strengthening conservation outcomes and policies.

}, keywords = {Asian tropics; Biodiversity; Comparative studies; Functional biology; Long-term ecological monitoring.}, issn = {0022-0949}, doi = {10.1242/jeb.252222}, url = {https://doi.org/10.1242/jeb.252222}, author = {Somanathan, Hema and Jain, Manjari and Habib, Bilal and Sane, Sanjay P. and Singh, Mewa} } @article {161131, title = {Targeted Bisulfite Sequencing and DNA Methylation Analysis in Rice Endosperm and Other Tissues.}, journal = {Methods Mol Biol}, volume = {2988}, year = {2026}, month = {2026}, pages = {71-82}, abstract = {

DNA methylation is a major epigenetic mark on chromatin. Tissue-specific DNA methylation in the regulatory regions of key genes modulates their tissue-specific expression. To study DNA methylation levels at specific sequence contexts across tissues or during various environmental conditions, whole-genome DNA methylation analysis is widely used. However, whole-genome methylation analysis is an expensive, time-consuming technique and requires specific skills. To understand the role of DNA methylation in a small number of candidate loci, targeted bisulfite (BS) PCR-sequencing analysis is an attractive option. Here, we describe a detailed method to understand DNA methylation by targeted-BS PCR analysis using rice endosperm tissues. This method can be readily extended to multiple monocots, across various tissues and various stress conditions.

}, keywords = {DNA Methylation, DNA, Plant, Endosperm, Epigenesis, Genetic, Genome, Plant, High-Throughput Nucleotide Sequencing, Oryza, Polymerase Chain Reaction, Sequence Analysis, DNA, Sulfites}, issn = {1940-6029}, doi = {10.1007/978-1-0716-4981-7_7}, author = {Pal, Avik Kumar and Gandhivel, Vivek Hari-Sundar and Shivaprasad, P V} } @article {166217, title = {Three new species of Sarasaeschna Karube \& Yeh, 2001 (Odonata: Anisoptera: Aeshnidae) from northeastern India; with a new record of Sarasaeschna khasiana (Lieftinck, 1968)}, journal = {Zootaxa}, volume = {5796}, year = {2026}, month = {21st April 2026}, type = {Article}, abstract = {

We erect three new species of Sarasaeschna Karube \& Yeh, 2001 (Odonata: Anisoptera: Aeshnidae): Sarasaeschna dosdewaensis sp. nov., S. nuboides sp. nov. and S. sigotaayo sp. nov., and provide a new record of S. khasiana (Lieftinck, 1968) based on specimens collected from northeastern India. We illustrate male caudal appendages of all Sarasaeschna and provide taxonomic keys to males (n=20) of all Sarasaeschna spp.

}, keywords = {Odonata, OdonataIndia, Sarasaeschna}, doi = {https://doi.org/10.11646/zootaxa.5796.2.3}, url = {https://www.mapress.com/zt/article/view/zootaxa.5796.2.3}, author = {SHANTANU JOSHI and DATTAPRASAD SAWANT and UJWALA PAWAR and FAHIM KHAN and REJOICE GASSAH and VIJAY ANAND ISMAVEL and Krushnamegh Kunte} } @article {163316, title = {Three{\textquoteright}s Company: Human infrastructure and diminishing savannas accentuate meso-carnivore interactions in a shared landscape of western India}, journal = {Biological Conservation}, volume = {313}, year = {2026}, month = { January 2026}, pages = {111618}, type = {Research Article}, abstract = {

Human modifications to natural landscapes negatively impact carnivore communities. Some species may yet benefit from habitat modifications by way of resource subsidisation or reduced competition, while trading-off heightened risks. We examined a meso-carnivore community comprising golden jackal\ Canis aureus, jungle cat\ Felis chaus, Indian fox\ Vulpes bengalensis\ and desert cat\ Felis lybica ornata\ in a semi-arid landscape of Kachchh, India. First, we mapped their potential habitats and gauged the extent of fragmentation as a measure of vulnerability. Using camera-trapping and indirect sign surveys within an occupancy modelling framework, we then examined species{\textquoteright} space use and interactions, incorporating the potential mediating influence of anthropogenic factors. Finally, we assessed temporal and fine-scale spatio-temporal co-occurrence. The most fragmented native habitat, open savanna, was positively associated with the occurrence of three of the four species. We found some evidence for body size-based dominance shaping patterns of species{\textquoteright} spatial overlap. Spatially co-occurring species also showed temporal overlaps; temporally overlapping species further seemed to aggregate at fine spatio-temporal scales. Human disturbance mediated species interactions, wherein species pairs tended to co-occur less frequently in human-modified areas (e.g., metalled roads). Rectifying policy surrounding savanna habitats informed by species space use and interactions and affording them protection may help preserve species, prevent potential competition-driven species loss and homogenisation of the biotic communities in semi-arid landscapes.

}, keywords = {Carnivores, Free-ranging dogs, Habitat use, Human impacts, Interspecific interactions, Shared landscapes, Tropics}, doi = {https://doi.org/10.1016/j.biocon.2025.111618}, url = {https://www.sciencedirect.com/science/article/pii/S000632072500655X?via\%3Dihub}, author = {Divyajyoti Ganguly and Arjun Srivathsa and Divya Vasudev and Uma Ramakrishnan} } @article {165751, title = {Transcriptional noise sets fundamental limits to decoding circadian clock phase from single-cell RNA snapshots}, journal = {iScience}, volume = {29}, year = {2026}, pages = {115394}, abstract = {

Summary The circadian clock drives rhythmic physiological variations, making accurate clock-phase measurement essential. Single-sample phase inference from bulk RNA is an exciting alternative to time-series methods, but its applicability to single cells remains unclear. Using multiplexed smFISH to quantify up to six core-clock genes in mouse fibroblasts, combined with a Gaussian process-based algorithm, we show that even with minimal technical dropouts, transcriptional noise in core-clock genes prevents reliable single-cell phase estimation. Simulations predict that measuring \~{}50 low-noise, clock-like oscillatory genes is required for accurate single-cell inference. In scRNA-seq data, non-core genes were too noisy, and adding hundreds of them did not improve accuracy. Remarkably, averaging smFISH counts from only three core-clock genes across \~{}70 cells enabled robust phase estimation. In desynchronized fibroblasts, spatially heterogeneous phases indicating local inter-cellular coupling were revealed only upon averaging, not at single-cell resolution. Coarse graining is, therefore, essential for circadian phase inference from RNA measurements alone.

}, keywords = {classification of bioinformatical subject, integrative aspects of cell biology, noise control, transcriptomics}, issn = {2589-0042}, doi = {https://doi.org/10.1016/j.isci.2026.115394}, url = {https://www.sciencedirect.com/science/article/pii/S2589004226007698}, author = {Anjoom Nikhat and Taniya Mandal and Nivedha Veerasubramanian and Shaon Chakrabarti} } @article {166238, title = {A Tubules-First Model for the Origin of Eukaryotic Membrane Traffic}, journal = {Annual Review of Biophysics}, volume = {55}, year = {2026}, pages = {301-322}, type = {Journal Article}, abstract = {

The discovery of membrane trafficking proteins in Asgard archaea{\textemdash}the closest archaeal relatives of eukaryotes{\textemdash}reveals the deep evolutionary roots of the eukaryotic endomembrane system. This review synthesizes genomic, structural, and functional studies of archaea and eukaryotes to explore how these ancient proteins contributed to the emergence of intracellular membranes. While Asgard archaea appear to lack the canonical machinery for coated vesicle formation, they encode a full complement of proteins involved in membrane tubulation, scission, tethering, and fusion. This molecular repertoire suggests that the archaeal ancestor of eukaryotes was capable of membrane remodeling, potentially via transient tubules. In early eukaryotes{\textemdash}following mitochondrial acquisition and internalization of the endoplasmic reticulum{\textemdash}tubules may have served as the principal carriers of membrane traffic. Coated vesicles{\textemdash}spherical vesicles that use scaffold proteins and sterol-rich membranes to stabilize high-curvature buds{\textemdash}may represent a later innovation prior to the last eukaryotic common ancestor. Archaea-derived tubular trafficking pathways play essential roles in modern eukaryotic cells.

}, keywords = {Asgard archaea; FECA; eukaryogenesis; evolutionary cell biology; first eukaryotic common ancestor; membrane traffic; membrane tubules.}, issn = {1936-1238}, doi = {https://doi.org/10.1146/annurev-biophys-021424-013933}, url = {https://www.annualreviews.org/content/journals/10.1146/annurev-biophys-021424-013933}, author = {Thattai, Mukund} } @article {165841, title = {Unifying theories in high-dimensional biophysics: approaches, challenges and opportunities}, year = {2026}, abstract = {
Across biological subdisciplines, the last decade has seen an explosion of high-dimensional datasets. At the ICTS workshop {\textquoteleft}Unifying Theories in High-Dimensional Biophysics{\textquoteright}, we discussed whether this high dimensionality poses a challenge or an opportunity for theoretically describing, understanding and predicting biological systems. We discussed methods, models and frameworks that can be used for this purpose. This Comment summarizes our discussions from the perspectives of individual participants.
} } @article {164002, title = {Unraveling functions of a novel miRNA-aquaporin module linked to rice domestication}, journal = {Springer Nature Link}, volume = {263}, year = {2026}, month = {11 February 2026}, abstract = {

Most of the cultivated rice originated from ancestors that were semi-aquatic plants, having semi-prostrate stems bearing negligible seeds. It is not known how domesticated rice achieved delicate water relations during the transition to irrigated and gradually terrestrial ecosystem. Here, we show the involvement of an aquaporin that is differentially expressed between cultivated and wild rice, contributing to yield-related traits. Small (s)RNA-sequencing and degradome analysis identified specific targeting of this aquaporin by differentially expressing a well-conserved micro(mi)RNA named miR169. Although miR169 was previously implicated in stress tolerance, its targeting of aquaporin or the consequences of such a targeting were unknown. Using whole-genome approaches, such as sRNA-sequencing, RNA-seq, CRISPR-knockout lines, and stress assays, we show the involvement of this regulatory module in water-stress-associated traits. In agreement with its importance in domestication and yield-related traits, a known QTL for stress tolerance overlapped with this aquaporin. These results indicate yet another involvement of sRNA-mediated module in crop domestication.

}, keywords = {Aquaporin, Domestication, Gene Silencing, MiRNA, PIP, Stress}, doi = {https://doi.org/10.1007/s00425-026-04932-0 }, url = {https://link.springer.com/article/10.1007/s00425-026-04932-0?error=server_error}, author = {T. N. Sujith and A. Archana and N. Anushree and P. V. Shivaprasad} } @article {158512, title = {Active drive towards elastic spinodals}, year = {2025}, abstract = {

Active matter, exemplified by adaptive living materials such as the actomyosin cytoskeleton, can navigate material parameter space, leading to unconventional mechanical responses. In particular, it can self-drive toward\ elastic spinodal\ regimes, where inhomogeneous floppy modes induce elastic degeneracy and enable a controlled interplay between rigidity loss and recovery. Proximity to such marginal states leads to stress localization and the formation of force chains that can be actively assembled and disassembled. Here we extend the classical notion of spinodal states to active solids and demonstrate how these extreme mechanical regimes can be actively accessed. Moreover, we show that in a nonlinear setting, crossing elastic spinodals generates new energy wells and makes force channeling an intrinsic feature of the emerging microstructure.

}, doi = {DOI: https://doi.org/10.1103/h2yp-d2s2}, url = {https://journals.aps.org/pre/abstract/10.1103/h2yp-d2s2}, author = {Ayan Roychowdhury and Madan Rao and Lev Truskinovsky} } @article {157488, title = {Additions to the moth (Lepidoptera) fauna of India from the eastern Himalaya and northeastern region: Part 2}, journal = {Tropical Lepidoptera Research}, volume = {35}, year = {2025}, month = {16 May 2025}, type = {Research Article}, abstract = {

Thirteen moth species,\ Pyrinioides oquiho\ Owada \& Kobayashi, 2020,\ Mellea atristrigulalis\ (Hampson, 1896) (Thyrididae),\ Rotunda rotundapex\ (Miyata \& Kishida, 1990) (Bombycidae),\ Metabraxas pectinella\ Yazaki, 2020 and\ Psilalcis inoueorum\ Sato, 2008 (Geometridae),\ Garudinia latana\ (Walker, 1863),\ Teulisna maculata\ Fang, 2000,\ Sesapa honbaensis\ Dubatolov \& Bucsek, 2013,\ Ovipennis milani\ (Černý, 2009),\ Nudina ankistro\ Volynkin, Huang, Bolotov \& Spitsyn, 2021,\ Nudina witti\ Spitsyn, Volynkin, Huang \& Bolotov, 2021 (Erebidae, Arctiinae),\ Lymantria\ (Beatria)\ hauensteinihauensteini\ Schintlmeister, 2004 (Erebidae, Lymantriinae), and\ Hepsidera lignea\ Swinhoe, 1902 (Eerebidae, Herminiinae) are reported from India for the first time. Of these records, two genera,\ Rotunda\ Wang, X. \& Zolotuhin, 2015 and\ Nudina\ Staudinger, 1887 are reported from India for the first time.

}, doi = {10.5281/zenodo.15359779}, url = {Additions to the moth (Lepidoptera) fauna of India from the eastern Himalaya and northeastern region: Part 2}, author = {Sanjay Sondhi and Rachit Pratap Singh and Ujawala Pawar and Krushnamegh Kunte} } @article {158949, title = {Alien plants and novel ecosystems in the Greater Tropics.}, year = {2025}, abstract = {

The tropics and subtropics, collectively the Greater Tropics, are home to most of Earth{\textquoteright}s biodiversity and humanity, and are undergoing unprecedented transformations driven by global change. In this Review, we assess how alien plants, an underappreciated component of these transformations, interact with other global changes, including land-use shifts, climate change and biotic attrition, to reshape socioecological systems in the Greater Tropics. Whereas many alien plants initially act as passengers of global change, others can become powerful drivers, reconfiguring ecological communities and catalysing novel ecosystem dynamics. Arising changes risk creating homogenized plant communities further disrupted by intense human pressure and social vulnerability. Drawing on insights from community ecology, biogeography and evolutionary theory, we examine the implications of these transformations and the potential for alien plants to both exacerbate and buffer the impact of global change. Given the rapid ecological shifts underway, we highlight the critical need for forwards-looking management that integrates ecological complexity with social realities. We advocate for adaptive, evidence-based frameworks {\textemdash} including nature-based solutions and the resist{\textendash}accept{\textendash}direct typology {\textemdash} that support both biodiversity and human well-being. A proactive, inclusive approach to managing alien plants is essential to safeguard socioecological resilience in the Greater Tropics.

}, doi = {10.1038/s44358-025-00068-3}, url = {https://doi.org/10.1038/s44358-025-00068-3 }, author = {Ninad Mungi and Mauro Galetti and Jayashree Ratnam and Desalegn Chala and Mar{\'\i}a Jos{\'e} San{\'\i}n and Jens-Christian Svenning} } @article {152899, title = {The alteration of structural network upon transient association between proteins studied using graph theory.}, journal = {Proteins}, volume = {93}, year = {2025}, month = {2025 Jan}, pages = {217-225}, abstract = {

Proteins such as enzymes perform their function by predominant non-covalent bond interactions between transiently interacting units. There is an impact on the overall structural topology of the protein, albeit transient nature of such interactions, that enable proteins to deactivate or activate. This aspect of the alteration of the structural topology is studied by employing protein structural networks, which are node-edge representative models of protein structure, reported as a robust tool for capturing interactions between residues. Several methods have been optimized to collect meaningful, functionally relevant information by studying alteration of structural networks. In this article, different methods of comparing protein structural networks are employed, along with spectral decomposition of graphs to study the subtle impact of protein-protein interactions. A detailed analysis of the structural network of interacting partners is performed across a dataset of around 900 pairs of bound complexes and corresponding unbound protein structures. The variation in network parameters at, around, and far away from the interface are analyzed. Finally, we present interesting case studies, where an allosteric mechanism of structural impact is understood from communication-path detection methods. The results of this analysis are beneficial in understanding protein stability, for future engineering, and docking studies.

}, keywords = {Algorithms, Allosteric Regulation, Databases, Protein, Models, Molecular, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Interaction Maps, Proteins}, issn = {1097-0134}, doi = {10.1002/prot.26606}, author = {Prabantu, Vasam Manjveekar and Tandon, Himani and Sandhya, Sankaran and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {160486, title = {Analyzing sub-millisecond timescale protein dynamics using eCPMG experiments.}, journal = {J Biomol NMR}, year = {2025}, month = {2025 Sep 17}, abstract = {

Cellular functions require biomolecules to transition among various conformational sub-states in the energy landscape. A mechanistic understanding of cellular functions requires quantitative knowledge of the kinetics, thermodynamics, and structural features of the biomolecules experiencing exchange between several states. High-power Relaxation Dispersion (RD) NMR experiments have proven very effective for such measurements if the exchange occurs in timescales ranging from microseconds to milliseconds. However, scanning the significantly larger kinetic window within the time limit of instrumental availability and sample stability requires careful optimization of experiments. Understanding biomolecular functions at a mechanistic level depends on fitting such experimental data to theoretical models. However, the reliability of the fit parameters depends on the measurement schemes and is sensitive to experimental noise. Here, we benchmark different measurement schemes along with theoretical models for sub-millisecond timescale exchange and determine the robustness of these models in providing information when the measurements contain noise. Our results show that kinetics can be measured reliably from such experiments. The structural features of the exchanging sub-states, encoded in the chemical shift differences between the states, can be fitted, albeit with significant uncertainties. Information about the minor states is difficult to obtain exclusively from the RD data due to large uncertainties and sensitivity to noise.

}, issn = {1573-5001}, doi = {10.1007/s10858-025-00475-w}, author = {Phale, Apurva and Tewari, Aishani and Tendulkar, Gayatri and Das, Ranabir and Srinivasan, Sivakumar and Chakrabarti, Kalyan S} } @article {156309, title = {Androgen receptor activation for breast cancer therapy.}, journal = {Nat Rev Cancer}, year = {2025}, month = {2025 Apr 24}, abstract = {

Breast cancer overwhelmingly affects women (approximately 1000:1 ratio of women to men), with around 80\% of cases driven by oncogenic oestrogen receptor-α (ERα) activity. Endocrine therapy, including surgical removal of ovaries (oophorectomy), aromatase inhibitors or pharmaceutical ERα ablation, has long been the cornerstone of treatment in ER+\ breast cancer. Although effective in localized disease, it fails against metastatic endocrine-resistant breast cancer, the primary cause of mortality. This underscores the need for new treatment strategies beyond targeting oestrogen and ERα. In this context, the androgen receptor (AR), a key player in breast cancer biology, has long been overlooked. In the normal breast, oestrogen drives mammary gland growth, while androgens counterbalance it. The majority of ER+\ breast cancers also express AR, and treatment strategies adapted from prostate cancer using AR antagonists have failed in clinical trials. Considering the role of AR in normal breast biology, this might have been the wrong approach. Instead of blocking AR, does it need to be activated?

Hickey et al. tackled this question, conducting a large-scale preclinical study using cell lines and patient-derived breast cancer models, including endocrine-resistant ones with\ ESR1\ and\ CCND1\ amplification or mutations. The authors used ChIP{\textendash}seq (chromatin immunoprecipitation followed by sequencing) to map genome-wide interactions of AR and ERα with chromatin under different hormonal conditions. When AR was activated with dihydrotestosterone (DHT) and ERα with oestradiol, AR hijacked the transcriptional program of ERα by sequestering shared transcriptional coactivators such as SRC3 and p300 from ERα genomic sites. In doing so, AR effectively displaced ERα from target chromatin, shutting down ERα-driven tumour growth.

This explained why past AR antagonists such as enzalutamide had failed; blocking AR removed a crucial tumour suppressor. However, AR agonists such as DHT or the selective, non-virilizing agonist enobosarm suppressed tumour growth in ER+\ breast cancer models.

Encouragingly, a phase II clinical trial (NCT02463032) confirmed that enobosarm was not only effective but also well tolerated in women who had exhausted standard endocrine therapies.

The study by Hickey et al. represents a paradigm shift, highlighting how the intricate cross-talk between steroid receptors, beyond a singular focus on ERα, can be strategically leveraged for breast cancer therapy. It also underscores the need for further research into the dynamic hormonal landscape in women, particularly the substantial hormonal shifts post-menopause, which may alter transcriptional programs and influence responses to endocrine therapy.

{\textquotedblleft}blocking AR removed a crucial tumour suppressor{\textquotedblright}

My lab explores transcriptional mechanisms of nuclear receptors and, inspired by the study discussed here, we are examining the ERα{\textendash}AR interplay across a range of oestradiol-to-DHT ratios to mimic shifts from pre- to post-menopause. Our initial findings suggest that ligand balance shapes receptor interactions, highlighting the need to consider ligand ratios for effective therapy.

}, issn = {1474-1768}, doi = {10.1038/s41568-025-00821-y}, url = {https://www.nature.com/articles/s41568-025-00821-y}, author = {Notani, Dimple} } @article {158508, title = {Announcement: Biotropica{\textquoteright}s New Subject Editors 2025}, year = {2025}, abstract = {

Biotropica, the flagship journal of the Association for Tropical Biology and Conservation, is a highly regarded source of original research on the ecology, conservation, and management of all tropical ecosystems, and on the biology and evolution of tropical organisms. We aim for timely, fair, transparent, and constructive reviews and editorial decisions on the 400{\textendash}500 manuscripts received yearly. We value a geographically diverse Editorial Board with broad expertise in tropical taxa and ecological, evolutionary, and conservation research, reflecting our diverse authorship and readership.

In 2024, we ran our second open call for service on our Editorial Board. This year, we selected seven new Subject Editors from a highly qualified pool (Figure\ 1). Their expertise includes taxa such as mammals, birds, epiphytes, and micro-organisms, and conceptual areas, such as habitat fragmentation, pollination, frugivory, restoration, and plant{\textendash}soil interactions. Our new Subject Editors represent a geographically diverse group of institutions in Brazil, India, Mexico, Poland, and the United States. Please join us in welcoming our new Subject Editors and thanking those who are rotating off the Editorial Board, which now comprises 64 members based in 20 countries. The open call for editorial service will be an annual call, so please consider serving on our Editorial Board in the future.

}, doi = {https://doi.org/10.1111/btp.70048}, url = {https://onlinelibrary.wiley.com/doi/10.1111/btp.70048?af=R}, author = {11. Jennifer S. Powers and Francis Q. Brearley, and Jayashree Ratnam and Eleanor M. Slade} } @article {155541, title = {Around the World in 26 Million Years: Diversification and Biogeography of Pantropical Grass-Yellow Eurema Butterflies (Pieridae: Coliadinae)}, journal = {Journal of Biogeography}, year = {2025}, month = {22 February 2025}, abstract = {

Grass-yellow butterflies (Eurema) are a group of pantropical Pieridae distributed throughout Asia, Australasia, Africa and the New World. However, little is known about their diversification, including the biogeographic mechanism(s) explaining their circumglobal distribution. We present the first densely sampled, time-calibrated phylogeny and biogeographic reconstruction of grass-yellows to confirm the monophyly of the genera, re-evaluate their taxonomy and infer the biogeographic events contributing to their worldwide distribution.

}, doi = {https://doi.org/10.1111/jbi.15107}, url = {https://onlinelibrary.wiley.com/doi/10.1111/jbi.15107}, author = {Jing V. Leong and P{\'a}vel Matos-Marav{\'\i} and Rayner N{\'u}{\~n}ez and Renato Nunes and Weijun Liang and Krushnamegh Kunte} } @article {157493, title = {Artery regeneration: Molecules, mechanisms and impact on organ function.}, journal = {Semin Cell Dev Biol}, volume = {171}, year = {2025}, month = {2025 May 02}, pages = {103611}, abstract = {

Replenishment of artery cells to repair or create new arteries is a promising strategy to re-vascularize ischemic tissue. However, limited understanding of cellular and molecular programs associated with artery (re-)growth impedes our efforts towards designing optimal therapeutic approaches. In this review, we summarize different cellular mechanisms that drive injury-induced artery regeneration in distinct organs and organisms. Artery formation during embryogenesis includes migration, self-amplification, and changes in cell fates. These processes are coordinated by multiple signaling pathways, like Vegf, Wnt, Notch, Cxcr4; many of which, also involved in injury-induced vascular responses. We also highlight how physiological and environmental factors determine the extent of arterial re-vascularization. Finally, we discuss different in vitro cellular reprogramming and tissue engineering approaches to promote artery regeneration, in vivo. This review provides the current understanding of endothelial cell fate reprogramming and explores avenues for regenerating arteries to restore organ function through efficient revascularization.

}, keywords = {Artery; Cellular reprogramming; Collateral arteries; Development; Endothelial cells; Genetic lineage tracing; Regeneration.}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2025.103611}, url = {https://www.sciencedirect.com/science/article/pii/S1084952125000217?via\%3Dihub}, author = {Ghosh, Swarnadip and Bishnoi, Bhavnesh and Das, Soumyashree} } @article {158958, title = {Assessing germline mutational profile and its clinicopathological associations in Triple Negative Breast Cancer.}, journal = {Cancer Genet}, volume = {296-297}, year = {2025}, month = {2025 Jun 18}, pages = {65-75}, abstract = {

BACKGROUND: Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (\>25 \%) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are, however, predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in India METHODS: Multigene NGS (next-generation sequencing) panel testing of Triple Negative Breast Cancer patients was conducted. All patients were offered pre-test and post-test counseling.

RESULTS: In our study cohort of 192 TNBC patients, median age at diagnosis was 47 years (23-78). Germline pathogenic mutations were identified in 28.6 \% cases. Of the 58 pathogenic mutations identified, BRCA1 accounted for 72.4 \% and BRCA2 for 13.8 \%. Eight pathogenic mutations were identified in non-BRCA genes associated with DNA damage response pathway. Ten novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100 K indicated that the novel mutations were unique.

CONCLUSIONS: Our study confirms the major proportion of mutations in BRCA1/2 genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Large scale studies are warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.

}, issn = {2210-7762}, doi = {10.1016/j.cancergen.2025.06.004}, author = {John, Jisha and Bapat, Ashwini and Gahlaut, Siddharth and Luke, Naveen and Kumar, Rahul and Thakur, Yashaswi and Mathew, Christina and Konnur, Aishwarya and Namewar, Namrata and Reddy, Ruhi and Nagarkar, Sanket and Nare, Smeeta and Thomas, George and Busheri, Laleh and Reddy, Asha and Kelkar, Devaki and Dixit, Santosh and Deshmukh, Chetan and Ul Mannan, Ashraf and Sabarinathan, Radhakrishnan and Radhakrishna, Selvi and Mishra, Rupa and Koppiker, Chaitanyanand B} } @article {158495, title = {Assessing ungulate response to conservation-oriented village relocations and their associated management practices in a tiger reserve in central India}, year = {2025}, abstract = {

Conservation-oriented village relocations are used as tools for wildlife conservation in developing nations like India, despite the potential sociocultural and economic costs associated with displacement. In tiger reserves in central India, abandoned village sites are developed as grasslands to improve tiger prey numbers. However, little is known about how village relocations and their associated management interventions influence ungulate habitat use. The aim of the study was to understand the impact of village relocations on ungulates by assessing how the intensity of habitat use by five ungulate species (sambar, chital, gaur, nilgai, wild pig), quantified using dung accumulation rates, changed with respect to time since relocation and distance from the edge of a site (relocated/active village) in the Satpura Tiger Reserve, central India. The intensity of use of relocated village sites by sambar, chital, gaur, and nilgai increased with time since relocation, while for wild pigs, it decreased. The intensity of habitat use by all five species of ungulates was negatively correlated with distance from the edge of the site. Our results suggest that village relocations coupled with grassland management activities lead to increased intensity of habitat use by some species and, over time, this may lead to increased populations of these large herbivores, aiding the recovery of large mammalian predators. While this study focused on the ecological implications of relocations, there is also a critical need to view relocations as coupled social-ecological systems to better understand their viability as conservation interventions.

}, doi = {10.1007/s10531-025-03101-1}, url = {https://link.springer.com/article/10.1007/s10531-025-03101-1}, author = {R. Yashaswi Rao and Mahesh Sankaran and Devcharan Jathanna and Anish Andheria} } @article {162692, title = {Associating cancer-related RNA structure disrupting SNPs in LincRNAs to function.}, journal = {BMC Genomics}, volume = {26}, year = {2025}, month = {2025 Dec 12}, pages = {1100}, abstract = {

BACKGROUND: Long intergenic non-coding RNAs (lincRNAs) and single nucleotide polymorphisms (SNPs) have been associated with cancers for years, yet the molecular mechanism is mostly unclear. The secondary structure of lincRNAs is often crucial for their biological function but can be disrupted by SNPs. However, only a small number of studies investigated how lincRNAs function through secondary structure. Given that the vast majority of cancer-related SNPs are located mainly in non-coding regions, there is a large potential for associating SNPs to disrupted structure in lincRNAs.

METHODS: To estimate the structural impacts of cancer-associated SNPs on lincRNAs, we predicted local secondary structures for lincRNAs and computed structural distances between structural ensembles of the wild-type and mutant sequences. Manual literature curation was performed to study the function of lincRNAs that are structurally disrupted by cancer-associated SNPs. By integrating with RBP binding sites annotation, we estimated the impacts of structural changes from cancer-associated SNPs on the protein binding of lincRNAs.

RESULTS: We predict 559 SNPs to cause significant structural disruption in 231 lincRNAs using RNAsnp (-value \< 0.1). In addition, we find that these disrupted regions have the potential to alter the binding ability of lincRNAs with RBPs. An example is the structural change in the lincRNA small nucleolar RNA host gene 25 (SNHG25), which overlaps the binding site of protein insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) in glioblastoma multiforme.

CONCLUSIONS: The results show the importance of the lincRNA secondary structure in understanding their biological function, especially the structural changes from SNPs in cancer. The predicted structural change in lincRNA SNHG25 holds a potential insight into the mechanism of protein IGF2BP2 in recognizing RNA methylation signals in glioblastoma multiforme.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-025-12226-0.

}, issn = {1471-2164}, doi = {10.1186/s12864-025-12226-0}, author = {Han, Xueer and Anthon, Christian and Geissler, Adrian Sven and Sabarinathan, Radhakrishnan and Seemann, Stefan Ernst and Havgaard, Jakob Hull and Gorodkin, Jan} } @article {152131, title = {Avenues towards reconciling wild and managed bee proponents.}, journal = {Trends Ecol Evol}, volume = {40}, year = {2025}, month = {2024 Dec 06}, pages = {7-10}, abstract = {

Bees are crucial for food security and biodiversity. However, managed bees are increasingly considered drivers of wild bee declines, leading to stakeholder conflicts and restrictive policies. We propose avenues to reconcile wild and managed bee proponents and point out knowledge gaps that hinder the development of evidence-based policies.

}, issn = {1872-8383}, doi = {10.1016/j.tree.2024.11.009}, author = {Beaurepaire, Alexis L and Hogendoorn, Katja and Kleijn, David and Otis, Gard W and Potts, Simon G and Singer, Theresa L and Boff, Samuel and Pirk, Christian and Settele, Josef and Paxton, Robert J and Raine, Nigel E and Tosi, Simone and Williams, Neal and Klein, Alexandra-Maria and Le Conte, Yves and Campbell, Joshua W and Williams, Geoffrey R and Marini, Lorenzo and Brockmann, Axel and Sgolastra, Fabio and Boyle, Natalie and Neuditschko, Markus and Straub, Lars and Neumann, Peter and Charri{\`e}re, Jean-Daniel and Albrecht, Matthias and Dietemann, Vincent} } @book {155537, title = {Bacterial Genomes Trees and Networks}, series = {Bacterial Genomes Trees and Networks}, volume = {1}, year = {2025}, pages = {254}, publisher = {Open Book Publishers}, organization = {Open Book Publishers}, abstract = {
Microbes form the {\textquotedblleft}unseen majority{\textquotedblright} of life on Earth, with bacteria at the forefront as both the architects of life{\textquoteright}s chemical foundations and agents of disease. But their story is far more complex. Bacteria thrive in diverse and extreme environments, driven by the dynamic evolution of their genomes. These tiny organisms wield an extraordinary ability to adapt, balancing genetic changes across generations with rapid physiological responses to environmental shifts.
In Bacterial Genomes, the evolutionary and regulatory processes that shape bacterial life are brought to life. This textbook offers a conceptual exploration of how bacterial genomes are organized, how they evolve, and how their genetic information is interpreted through intricate molecular networks. Drawing on both cutting-edge research and the historical milestones that shaped microbiology, it illuminates how bacteria navigate the intersection of genetic adaptation and ecological resilience.
Designed for college students, interdisciplinary researchers, and even the determined amateur, Aswin Seshasayee moves beyond technical jargon to provide a thought-provoking synthesis of bacterial evolution and adaptation. Unlike traditional genomics texts, this book blends historical insights with contemporary discoveries, offering a fresh perspective on the role of bacteria in shaping the living world.
}, isbn = {Paperback: 978-1-80511-495-6; Hardback: 978-1-80511-496-3; PDF 978-1-80511-497-0; HTML:978-1-80511-499-4; EPUB:978-1-80511-498-7}, doi = {https://doi.org/10.11647/OBP.0446}, url = {https://www.openbookpublishers.com/books/10.11647/OBP.0446}, author = {Aswin Sai Narain Seshasayee} } @article {158514, title = {Balancing act: persistence of the red fox in the dog-dominated landscapes of the Trans-Himalaya}, year = {2025}, abstract = {

Free-ranging dogs pose a growing threat to wildlife globally. In the Indian Trans-Himalaya, growing populations of dogs raise concerns about their impact on native carnivores. Red foxes in Spiti Valley share spatial and dietary niches with dogs, despite intraguild killing pressure. Sampling across a gradient of dog density in the winter, we investigated two potential mechanisms that might enable the observed sympatry between foxes and dogs. Using a cue-based foraging station experiment, we investigated the use of anti-predatory vigilance by foxes. We also used a camera trap array to assess temporal partitioning between the two canids and the relative abundance of foxes across the dog-density gradient. Foxes only increased vigilance in response to simulated dog presence at sites with high dog densities. We found that temporal overlap was low across the dog-density gradient in the winter. Fox relative abundances increased with dog-density, indicating a potential lack of apparent top-down effects by dogs. Our findings suggest that while temporal partitioning may reduce encounters, increased vigilance in high-dog-density areas may be crucial for coexistence. We highlight the complex behavioural mechanisms facilitating the persistence of a generalist mesocarnivore in the face of increasing pressure from free-ranging dogs and underscore the need for similar investigations in other human-dominated landscapes.

}, doi = {https://doi.org/10.1098/rspb.2025.0333}, url = {https://royalsocietypublishing.org/doi/10.1098/rspb.2025.0333}, author = {Herman Ramesh and Rumaan Malhotra and Sai Khurana and Deepraj Pandey and Tandup Chhering and Kulbhushansingh Ramesh Suryawanshi} } @article {161979, title = {Beyond degradation tags: How FAT10 and ubiquitin shape substrate energy landscapes.}, journal = {Essays Biochem}, year = {2025}, month = {2025 Nov 06}, abstract = {

Protein degradation via the proteasome is a fundamental process for maintaining proteostasis. The post-translational modification of substrate proteins by ubiquitin and the ubiquitin-like modifier FAT10 targets them for proteasomal degradation. While ubiquitin and FAT10 have traditionally been perceived as passive signals for proteasomal targeting, emerging evidence indicates that they actively influence both the thermodynamic and conformational landscapes of their respective substrates. In this review, we explore recent mechanistic insights into how the modification site and the intrinsic characteristics of the modifier dictate substrate stability. Ubiquitin destabilizes proteins in a site-specific manner through entropic restriction or enthalpic disruption, thereby modulating degradation efficiency. It is noteworthy that well-folded ubiquitin substrates require unfoldases such as p97/valosin-containing protein for successful degradation. Conversely, FAT10 acts as a significant destabilizer across various substrates due to its inherent low thermodynamic stability and flexible structure, thereby facilitating rapid degradation independent of unfoldases. These findings redefine post-translational tagging as an active regulator of protein fate and propose novel strategies for manipulating protein turnover within disease contexts.

}, keywords = {Protein{\textendash}protein interactions; thermodynamics; ubiquitin{\textendash}proteasome system.}, issn = {1744-1358}, doi = {10.1042/EBC20253034}, author = {Ravichandran, Aravind and Sivakumar, Adarshan and Das, Ranabir} } @article {159714, title = {Biodiversity effects on seedling growth are modified by light environment across functional groups.}, journal = {Ecol Appl}, volume = {35}, year = {2025}, month = {2025 Jul}, pages = {e70087}, abstract = {

Numerous studies have shown that biodiversity influences the functioning of ecosystems over space and time. The sensitivity of such biodiversity-ecosystem effects to environmental heterogeneity, however, remains poorly understood. In forests, seedling recruitment is a critical phase of forest dynamics, and this phase is highly sensitive to environmental heterogeneity and biotic interactions with surrounding plants. In closed-canopy forests, local variation in light due to variation in canopy cover can result in heterogeneous microenvironments that can enhance or constrain seedling growth and ultimately forest regeneration. Here, we ask, how do light and seedling diversity influence the growth and biomass gain of seedlings in tropical forests? We tested the effects of and interactions between seedling diversity and light availability on the growth of seedlings consisting of tropical broad-leaved evergreen and deciduous forest species using a fully factorial manipulated experiment in the Andaman Islands, India. We compared results from this manipulated experiment with field observations from a long-term forest plot. We show that during the critical seedling establishment phase, species richness and light availability additively increased biomass accumulation of seedlings in communities consisting of evergreen and deciduous species. Moreover, the positive effect of light on biomass gain was consistent across species in these different functional groups. We conclude that the diversity effect on biomass gain is explained more by species complementarity across conditions rather than by compensatory effects by different species under different light conditions or simple probabilistic effects of including faster growing species in species-rich communities. Taken together, our results show that the potential for biodiversity to increase ecosystem functioning in seedling communities is modified by light availability. Although many factors are often important in designing replanting efforts in forest management or restoration, our results suggest that key factors are likely to be the interaction between neighborhood diversity and canopy-mediated light on forest understory, which can be managed to enhance seedling establishment at the early stages of forestry projects aimed at maintaining forest diversity, composition, and functioning.

}, keywords = {Biodiversity, Biomass, Forests, India, Light, Seedlings, Trees}, issn = {1051-0761}, doi = {10.1002/eap.70087}, author = {Anujan, Krishna and Shabnam, Alisha and Ali, Irfan and Gummadi, Ashok Kumar and Sankaran, Mahesh and Krishnadas, Meghna and Naeem, Shahid} } @article {161133, title = {Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Oct 23}, pages = {9370}, abstract = {

Effective clearance of Mycobacterium tuberculosis (Mtb) requires targeting drug-tolerant populations within host macrophages. Here, we show that macrophage metabolic states govern redox heterogeneity and drug response in intracellular Mtb. Using a redox-sensitive fluorescent reporter (Mrx1-roGFP2), flow cytometry, and transcriptomics, we found that macrophages with high oxidative phosphorylation (OXPHOS) and low glycolysis harbor reductive, drug-tolerant Mtb, whereas glycolytically active macrophages generate mitochondrial ROS via reverse electron transport, imposing oxidative stress on Mtb and enhancing drug efficacy. Computational and genetic analyses identified NRF2 as a key regulator linking host metabolism to bacterial redox state and drug tolerance. Pharmacological reprogramming of macrophages with the FDA-approved drug meclizine (MEC) shifted metabolism towards glycolysis, suppressed redox heterogeneity, and reduced Mtb drug tolerance in macrophages and mice. MEC exhibited no adverse interactions with frontline anti-TB drugs. These findings demonstrate the therapeutic potential of host metabolic reprogramming to overcome Mtb drug tolerance.

}, keywords = {Animals, Antitubercular Agents, Drug Tolerance, Energy Metabolism, Female, Glycolysis, Humans, Macrophages, Mice, Mice, Inbred C57BL, Mitochondria, Mycobacterium tuberculosis, NF-E2-Related Factor 2, Oxidation-Reduction, Oxidative Phosphorylation, Oxidative Stress, Reactive Oxygen Species, Tuberculosis}, issn = {2041-1723}, doi = {10.1038/s41467-025-64407-w}, author = {Yadav, Vikas and Sahoo, Sarthak and Malhotra, Nitish and Mishra, Richa and Sreedharan, Sreesa and Rajmani, Raju S and Shanmugam, Siva and Shandil, Radha K and Narayanan, Shridhar and Thacker, Vivek V and Laxman, Sunil and Jolly, Mohit Kumar and Seshasayee, Aswin Sai Narain and Singh, Amit} } @article {154351, title = {BPS2025 - Recent developments in integrative structural modeling of macromolecular assemblies}, journal = {Biophysical Journal}, volume = {124}, year = {2025}, month = {13 February 2025}, chapter = {323A}, abstract = {

Integrative structure determination allows us to determine the structures of large macromolecular assemblies by combining data from complementary experimental methods with physical principles, statistical inference, and prior models. This talk will focus on efforts towards improving integrative modeling by my group in the last few years. Specifically, I will describe methods to optimize coarse-grained representations, annotate precision for integrative models, and obtain binding sites for intrinsically disordered regions. First, we developed methods to optimize the coarse-graining of subunits for an integrative modeling system, based on the amount of input information. The optimization is based on Bayesian model selection and we demonstrate that the optimized representations enable efficient sampling and result in models that fit the input data well. Second, we developed an efficient method to annotate regions of high- and low-precision in an integrative model ensemble. Low-precision regions can suggest where the next set of experimental data would be most impactful and high-precision regions can be used for identifying binding interfaces and suggesting new mutations. Finally, we developed a method to identify binding sites for intrinsically disordered regions (IDRs) of proteins in assemblies. Often, IDRs are challenging to localize in macromolecular assemblies, since they are associated with sparse structural as well as other interaction data. I will discuss a recent deep-learning method that we developed to predict binding regions for IDRs in large assemblies; the method outperforms AlphaFold3 on this task on benchmarks. Finally, I will also discuss emerging frontiers in the field: methods for utilizing data from cryo-electron tomography and methods that build upon AI-based structure predictions. In all, these methods will result in an improved spatio-temporal characterization of macormolecular structures in cells.

}, doi = {10.1016/j.bpj.2024.11.1782}, url = {https://www.cell.com/biophysj/fulltext/S0006-3495(24)02510-4}, author = {Shruthi Viswanath} } @article {154149, title = {BPS2025 - Structural network comparison of domains across remote homologs}, journal = {Biophysical Journal}, volume = {124}, year = {2025}, month = {13 February 2025}, pages = {215a-216a}, chapter = {215a}, abstract = {

Protein domains serve as essential structural and functional units within proteins, with their organization largely defined by a limited set of domain architectures. Traditional structural comparison metrics like RMSD, TM-score, and GDT scores focus on protein backbones and often fail to capture the subtleties of inter-domain interactions and intradomain communication, which are crucial for diverse protein functions. Our work employs the use of protein structural network (PSN) analysis, which includes main-chain and side-chain atoms to investigate homologous domains. The PSN is a node and edge representation of amino acid residues, where an edge is defined between a pair of nodes (residues) that are within the interaction distance threshold. We examined the homologous domain pairs, in association with another homologous domain pair within and across proteins (type 1 and 2), vs. homologous domain pairs connected to structurally unrelated domains (type 2) by comparing their PSN. The study revealed significant variability in the network parameters (like degree change, hub preservation) between these types of domain comparisons. These findings may suggest mechanisms of having different domain functionality and structural integrity albeit maintaining similar structures. Furthermore, through graph spectral analysis, the networks of domain pairs in different types were studied to understand residue organization within individual domains and how the domain interaction partnership affects the domain structure and function. The network of two domains interacting permanently and transiently was also studied to reveal striking differences in their interfaces and beyond. This study would pave to better understand domain interactions in monomeric multi-domain proteins and eventually enable better homology differentiation of domains, thereby shedding light of folding of small multi-domain proteins.

}, doi = {10.1016/j.bpj.2024.11.1190}, url = {https://www.cell.com/biophysj/fulltext/S0006-3495(24)01914-3}, author = {Sidhanta Swayam Prakash Das and Vasam Manjveekar Prabantu and Ramanathan Sowdhamini and Narayanaswamy Srinivasan} } @article {155676, title = {Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors.}, journal = {J Cell Biol}, volume = {224}, year = {2025}, month = {2025 May 05}, abstract = {

Membrane contact sites (MCS) between the plasma membrane (PM) and endoplasmic reticulum (ER) regulate Ca2+ influx. However, the mechanisms by which cells modulate ER-PM MCS density are not understood, and the role of Ca2+, if any, in regulating these is unknown. We report that in Drosophila photoreceptors, MCS density is regulated by the Ca2+ channels, TRP and TRPL. Regulation of MCS density by Ca2+ is mediated by Drosophila extended synaptotagmin (dEsyt), a protein localized to ER-PM MCS and previously shown to regulate MCS density. We find that the Ca2+-binding activity of dEsyt is required for its function in vivo. dEsytCaBM, a Ca2+ non-binding mutant of dEsyt is unable to modulate MCS structure. Further, reconstitution of dEsyt null photoreceptors with dEsytCaBM is unable to rescue ER-PM MCS density and other key phenotypes. Thus, our data supports a role for Ca2+ binding to dEsyt in regulating ER-PM MCS density in photoreceptors thus tuning signal transduction during light-activated Ca2+ influx.

}, keywords = {Animals, Calcium, Calcium Signaling, Cell Membrane, Drosophila melanogaster, Drosophila Proteins, Endoplasmic Reticulum, Photoreceptor Cells, Invertebrate, Synaptotagmins, Transient Receptor Potential Channels}, doi = {10.1083/jcb.202407190}, author = {Nath, Vaisaly R and Krishnan, Harini and Mishra, Shirish and Raghu, Padinjat} } @article {158956, title = {Caenorhabditis elegans germline flux pulls its stem-cell niche cells into shape.}, journal = {J Biosci}, volume = {50}, year = {2025}, month = {2025}, abstract = {

Morphogenesis is the process by which tissues and organs acquire their unique shapes and functions. Several cellular events, including cell shape changes, cell movement, cell proliferation, apoptosis, and others, act in concert to sculpt an organ. While these cellular behaviors are well-recognized to be essential for morphogenesis, whether organ-scale dynamics influence these cellular processes has remained unresolved. In a recent study published in , Tolkin (2024) investigated the mechanisms underlying the dramatic morphogenesis of the distal tip cell (DTC), a leader cell and germline stem-cell niche in the gonad (Byrd 2014; Lee 2016). They uncovered a novel {\textquoteright}hitch-and-tow{\textquoteright} mechanism whereby germline flux drives a complex change in DTC shape. This work sheds light on how mechanical forces at the organ level influence cellular morphogenesis.

}, keywords = {Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Movement, Cell Proliferation, Cell Shape, Germ Cells, Gonads, Morphogenesis, Stem Cell Niche, Stem Cells}, issn = {0973-7138}, author = {Agarwal, Priti} } @article {157485, title = {Caliphaea sinuofurcata sp. nov. (Odonata: Zygoptera: Calopterygidae) from Arunachal Pradesh, India}, journal = {Zootaxa}, volume = {5637}, year = {2025}, month = {20 May 2025}, pages = {139-154}, type = {Research Article}, chapter = {139}, abstract = {

We describe a new species,\ Caliphaea sinuofurcata\ sp. nov.,\ based on two male and one female specimens collected from Upper Siang District and Lower Dibang Valley District, Arunachal Pradesh, India. The newly described species can be distinguished from its congeners by characteristic shape of paraproct and genital ligula. Additionally, we provide illustrations of the male caudal appendages for all known\ Caliphaea\ spp.

}, doi = {10.11646/zootaxa.5637.1.6}, url = {https://mapress.com/zt/article/view/zootaxa.5637.1.6}, author = {DATTAPRASAD SAWANT and SHANTANU JOSHI and UJWALA PAWAR and VIRAJ NAWGE and Krushnamegh Kunte} } @article {162688, title = {Cold and lithium delay forgetting of olfactory memories in Caenorhabditis elegans.}, journal = {Nat Neurosci}, year = {2025}, month = {2025 Dec 18}, abstract = {

The persistence of memory reflects not only how it is formed but also how forgetting is delayed. The mechanisms controlling forgetting remain obscure, and in particular it is unclear to what degree this process is actively regulated. We discovered that cold exposure delays forgetting of specific olfactory memories by more than eight-fold and that adaptation to cold abolishes this effect. To study the underlying mechanism, we performed RNA sequencing, mutant analyses and pharmacological assays. Here we show that regulation of membrane properties underlies the presence and absence of cold-induced delayed forgetting. Furthermore, lithium can also delay forgetting in cold-sensitive worms but not in cold-tolerant worms; this effect involves downregulation of the diacylglycerol pathway in AWC neurons and long-term suppression of activity in the downstream AIY interneurons. Thus, the genetic tractability of worms might be harnessed to study the mechanism of action of lithium and cold exposure and, more fundamentally, how memory is stored and lost.

}, issn = {1546-1726}, doi = {10.1038/s41593-025-02143-6}, author = {Landschaft-Berliner, Dana and Goldstein, Kesem and Teichman, Guy and Anava, Sarit and Gingold, Hila and Salzberg, Yehuda and Rieger, Itai and Levy, Noam and Pechuk, Vladyslava and Setty, Hagar and Agarwal, Priti and Sagi, Dror and Cohen, Dror and Nikelshparg, Evelina and Ben-Zvi, Anat and Miranda-Vizuete, Antonio and Zaidel-Bar, Ronen and Oren-Suissa, Meital and Rechavi, Oded} } @article {158955, title = {Combating Tuberculosis: Obstacles, Innovations, and the Road Ahead.}, journal = {ACS Infect Dis}, volume = {11}, year = {2025}, month = {2025 Jul 11}, pages = {1754-1755}, issn = {2373-8227}, doi = {10.1021/acsinfecdis.5c00495}, author = {Sundaramurthy, Varadharajan and Strauss, Erick} } @article {157495, title = {Combining lineage correlations and a small molecule inhibitor to detect circadian control of the cell cycle}, journal = {Cell Press}, volume = {28}, year = {2025}, month = {18 April 2025}, abstract = {

Chronotherapy offers an exciting possibility for improving cancer treatments by leveraging the influence of the circadian clock on the cell cycle. While several molecular interactions coupling the two oscillators have been identified, whether they lead to emergent control of cellular proliferation remains unclear. Using stochastic simulations, we demonstrate that the established gene networks underlying the two oscillators are sufficient to generate lineage correlations in cell cycle times, as observed in single-cell microscopy data. The interactions also create a {\textquoteleft}therapeutic window{\textquoteright} between cancer and normal cell proliferation peaks that can be leveraged for chronotherapy. Surprisingly, our model predicts that KL001, a clock inhibitor, minimally affects population growth but significantly alters lineage correlations. Our results suggest that clock control of the cell cycle may not be detectable by measuring changes in population dynamics, but combining measurements of lineage correlations with KL001 treatment may provide a more sensitive approach to detecting the coupling.

}, doi = {https://doi.org/10.1016/j.isci.2025.112269}, url = {https://www.sciencedirect.com/science/article/pii/S2589004225005309}, author = {Anjoom Nikhat and Arsh Shaikh and Shaon Chakrabarti} } @article {156901, title = {Combining lineage correlations and a small molecule inhibitor to detect circadian control of the cell cycle.}, journal = {iScience}, volume = {28}, year = {2025}, month = {2025 Apr 18}, pages = {112269}, abstract = {

Chronotherapy offers an exciting possibility for improving cancer treatments by leveraging the influence of the circadian clock on the cell cycle. While several molecular interactions coupling the two oscillators have been identified, whether they lead to emergent control of cellular proliferation remains unclear. Using stochastic simulations, we demonstrate that the established gene networks underlying the two oscillators are sufficient to generate lineage correlations in cell cycle times, as observed in single-cell microscopy data. The interactions also create a {\textquoteright}therapeutic window{\textquoteright} between cancer and normal cell proliferation peaks that can be leveraged for chronotherapy. Surprisingly, our model predicts that KL001, a clock inhibitor, minimally affects population growth but significantly alters lineage correlations. Our results suggest that clock control of the cell cycle may not be detectable by measuring changes in population dynamics, but combining measurements of lineage correlations with KL001 treatment may provide a more sensitive approach to detecting the coupling.

}, keywords = {Cell biology; Small molecule.}, issn = {2589-0042}, doi = {10.1016/j.isci.2025.112269}, url = {https://www.sciencedirect.com/science/article/pii/S2589004225005309?via\%3Dihub}, author = {Nikhat, Anjoom and Shaikh, Arsh and Chakrabarti, Shaon} } @article {152167, title = {Comparative analysis of permanent and transient domain-domain interactions in multi-domain proteins.}, journal = {Proteins}, volume = {93}, year = {2025}, month = {2025 Jan}, pages = {197-208}, abstract = {

Protein domains are structural, functional, and evolutionary units. These domains bring out the diversity of functionality by means of interactions with other co-existing domains and provide stability. Hence, it is important to study intra-protein inter-domain interactions from the perspective of types of interactions. Domains within a chain could interact over short timeframes or permanently, rather like protein-protein interactions (PPIs). However, no systematic study has been carried out between two classes, namely permanent and transient domain-domain interactions. In this work, we studied 263 two-domain proteins, belonging to either of these classes and their interfaces on the basis of several factors, such as interface area and details of interactions (number, strength, and types of interactions). We also characterized them based on residue conservation at the interface, correlation of residue motions across domains, its involvement in repeat formation, and their involvement in particular molecular processes. Finally, we could analyze the interactions arising from domains in two-domain monomeric proteins, and we observed significant differences between these two classes of domain interactions and a few similarities. This study will help to obtain a better understanding of structure-function and folding principles of multi-domain proteins.

}, keywords = {Binding Sites, Databases, Protein, Humans, Models, Molecular, Protein Binding, Protein Domains, Protein Folding, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Proteins}, issn = {1097-0134}, doi = {10.1002/prot.26581}, author = {Sidhanta, Swayam Prakash Das and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {162679, title = {Computational Analyses of Bifurcated Inter-Protein Interactions in Protein-Protein Assemblies Reveal Their Pivotal Role in Conferring Stability.}, journal = {Proteins}, year = {2025}, month = {2025 Nov 28}, abstract = {

Majority of the proteome is constituted by oligomers and their function is governed by underlying protein-protein interactions. Interfacial residues, namely residues right at the interface of two protein chains, are known to confer stability and specificity in dimers. However, other interactions play a significant role in the formation and maintenance of oligomers in protein assemblies as well. Inter-protein bifurcated interactions are those where one residue simultaneously interacts with two residues belonging to two neighboring protein chains. The characteristic features of such higher-order interactions remain largely unexplored and unknown. In this study, we focused on residues specifically involved in bifurcated interactions (referred as RBI). We examine the bifurcated inter-protein interactions by assembling a dataset of protein assemblies of known 3D structures. We have characterized the type of interactions and the residues involved in the interactions using parameters like energy contributions and conservation scores. We find that the residues participating in bifurcated inter-protein interactions contribute more to the stability of the complex than other interfacial residues. Furthermore, we have presented examples where mutation of a residue involved in a bifurcated interaction results in detrimental outcomes. This study highlights the significance of inter-protein bifurcated interactions that contribute to the stability of multiple interfaces in protein oligomers and hence contribute to the expansion of the understanding of protein assemblies.

}, issn = {1097-0134}, doi = {10.1002/prot.70090}, author = {Bheemireddy, Sneha and Menon, Revathy and Chavali, Sreenivas and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {153398, title = {Computational analysis of the effect of a binding protein (RbpA) on the dynamics of Mycobacterium tuberculosis RNA polymerase assembly.}, journal = {PLoS One}, volume = {20}, year = {2025}, month = {2025}, pages = {e0317187}, abstract = {

BACKGROUND: RNA polymerase-binding protein A (RbpA) is an actinomycetes-specific protein crucial for the growth and survival of the pathogen Mycobacterium tuberculosis. Its role is essential and influences the transcription and antibiotic responses. However, the regulatory mechanisms underlying RbpA-mediated transcription remain unknown. In this study, we employed various computational techniques to investigate the role of RbpA in the formation and dynamics of the RNA polymerase complex.

RESULTS: Our analysis reveals significant structural rearrangements in RNA polymerase happen upon interaction with RbpA. Hotspot residues, crucial amino acids in the RbpA-mediated transcriptional regulation, were identified through our examination. The study elucidates the dynamic behavior within the complex, providing insights into the flexibility and functional dynamics of the RbpA-RNA polymerase interaction. Notably, potential allosteric mechanisms, involving the interface of subunits α1 and α2 were uncovered, shedding light on how RbpA modulates transcriptional activity.

CONCLUSIONS: Finally, potential ligands meant for the α1-α2 binding site were identified through virtual screening. The outcomes of our computational study serve as a foundation for experimental investigations into inhibitors targeting the RbpA-regulated dynamics in RNA polymerase. Overall, this research contributes valuable information for understanding the intricate regulatory networks of RbpA in the context of transcription and suggests potential avenues for the development of RbpA-targeted therapeutics.

}, keywords = {Bacterial Proteins, Binding Sites, DNA-Directed RNA Polymerases, Molecular Dynamics Simulation, Mycobacterium tuberculosis, Protein Binding, Transcription, Genetic}, issn = {1932-6203}, doi = {10.1371/journal.pone.0317187}, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0317187}, author = {Bheemireddy, Sneha and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {158502, title = {Computational exploration of Arabidopsis thaliana N-Myc downregulated-like-1 for protein{\textendash}protein interaction and phylogenetic conservation}, year = {2025}, abstract = {

N-Myc downregulated-like (NDL) proteins belong to the α/β-hydrolase-fold-containing protein family. NDLs are interacting partners of G-protein subunits which are involved in abiotic and biotic stress signaling mechanisms in plants. Three NDLs (NDL1, NDL2, and NDL3) have been identified in\ Arabidopsis thaliana. The NDL1 interactome reveals its interaction with numerous proteins involved in diverse plant functions, suggesting its role in various signaling mechanisms. The current study was designed to explore the level of conservation of NDL proteins across the plant kingdom to analyze protein structure for the conserved sites involved in protein{\textendash}protein interactions. We analyzed NDL proteins from different plant groups for sequence conservation patterns through phylogenetic and motif analyses. Subsequently, homology-based models were built for NDLs and their selected interactors using MODELLER, and interaction sites were also analyzed using molecular docking. Overall, our study revealed sequence conservation within the NDL family and the presence of several conserved motifs across diverse plant groups. Additionally, docking analysis suggests that two specific regions, spanning positions 40{\textendash}50 and 135{\textendash}170 in the NDL1 structure, may serve as hotspots for various protein{\textendash}protein interactions.

}, doi = {10.1007/s12038-025-00520-8 }, url = {https://link.springer.com/article/10.1007/s12038-025-00520-8}, author = {Abhishek Kanojia and Asani Bhaduri and Soumya Nayak and R Sowdhamini and Yashwanti Mudgil} } @article {161125, title = {Computational structural analysis sheds light on the molecular grammar of gap junction proteins.}, journal = {Biochimie}, year = {2025}, month = {2025 Oct 06}, abstract = {

Gap junctions are multimeric intercellular channels that permit ions and small molecules to pass directly from one cell to another. Despite being fundamental to multicellular life, these channels are formed by distantly related protein families: innexins in invertebrates and connexins in vertebrates. Vertebrates also express pannexins, distant homologues of primordial innexins, which only form hemichannels. While these families have diverse sequences and different oligomeric states, their monomeric structures are highly similar. We generated structure-guided sequence alignments to establish equivalent residues across innexins, connexins, and pannexins. Further, computational approaches for determining protein-protein interaction hotspots, residue conservation, accessible surface area and local conformations of residues, provide insights into the relationships between residue positions and channel properties. We find that exposed transmembrane residues of TM1 and TM2 are more conserved than those in TM3 and TM4, especially in connexins and pannexins. Moreover, we see that residues in the extracellular extended hairpins of pannexins show more conformational flexibility, in variable protein blocks, than equivalent residues in connexins. This hints that the rigidity of this element could be a prerequisite for hemichannel docking. Finally, we identify inter- and intra-hemichannel interface hotspots that are positionally conserved across the families, implying their role in hemichannel and, ultimately, gap junction formation. Such analyses reveal a molecular grammar that underlies gap junction design and offer a basis for targeted perturbation of channel properties.

}, issn = {1638-6183}, doi = {10.1016/j.biochi.2025.10.001}, author = {Pathak, Aditi and Sowdhamini, Ramanathan} } @article {152902, title = {Conformational diversity in class C GPCR positive allosteric modulation.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Jan 13}, pages = {619}, abstract = {

The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to the transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G protein binding and activation. The mGlu receptors signal transduction can be allosterically potentiated by positive allosteric modulators (PAMs) binding to the 7TMs, which are of therapeutic interest in various neurological disorders. Here, we report the cryoEM structures of metabotropic glutamate receptor 5 (mGlu) purified with three chemically and pharmacologically distinct PAMs. We find that the PAMs modulate the receptor equilibrium through their different binding modes, revealing how their interactions in the 7TMs impact the mGlu receptor conformational landscape and function. In addition, we identified a PAM-free but agonist-bound intermediate state that also reveals interactions mediated by intracellular loop 2. The activation of mGlu receptor is a multi-step process in which the binding of the PAMs in the 7TM modulates the equilibrium towards the active state.

}, keywords = {Allosteric Regulation, Animals, Cryoelectron Microscopy, Glutamic Acid, HEK293 Cells, Humans, Models, Molecular, Protein Binding, Protein Conformation, Protein Domains, Receptor, Metabotropic Glutamate 5, Receptors, Metabotropic Glutamate, Signal Transduction}, issn = {2041-1723}, doi = {10.1038/s41467-024-55439-9}, author = {Cannone, Giuseppe and Berto, Ludovic and Malhaire, Fanny and Ferguson, Gavin and Fouillen, Aurelien and Balor, St{\'e}phanie and Font-Ingles, Joan and Llebaria, Amadeu and Goudet, Cyril and Kotecha, Abhay and Vinothkumar, Kutti R and Lebon, Guillaume} } @article {162686, title = {Conservation Genomics-Making a Difference.}, journal = {Mol Ecol}, volume = {34}, year = {2025}, month = {2025 Dec}, pages = {e70191}, abstract = {

Conservation genomics has increasingly transitioned from a promising concept to a science that integrates a range of advanced analytical approaches, providing new insights into inbreeding, genetic load, demographic history and adaptive divergence in species of conservation concern. Yet, questions remain about how effectively these advances translate into practical conservation action. This Special Issue, Conservation Genomics-Making a Difference, brings together 37 papers that collectively assess how genomic data are contributing to conservation science and management. The contributions encompass empirical studies, reviews, and perspectives that together demonstrate how genomic tools are now used to identify management units, quantify inbreeding, analyse inbreeding depression, reveal adaptive variation, forecast genomic vulnerability under climate change, and guide genetic rescue and assisted migration. Several papers show direct integration of genomics into conservation planning, including fisheries management, guiding restoration of endangered or habitat-forming species, and monitoring of genetic indicators under the Convention on Biological Diversity. Others highlight emerging questions in conservation, such as the significance of structural variation, and the genomic basis of invasiveness. However, persistent challenges remain, notably in bridging the gap between research and policy, uneven global distribution of genomic resources, and translating complex analyses into practical management advice. Nevertheless, the advances presented in the 37 papers show that conservation genomics is moving beyond its early theoretical and technical focus towards real-world applications. The field is maturing and is increasingly fulfilling its promise to make a real difference for populations, species, and ecosystems.

}, keywords = {Animals, Conservation of Natural Resources, Endangered Species, Genetics, Population, Genomics, Inbreeding}, issn = {1365-294X}, doi = {10.1111/mec.70191}, author = {Hansen, Michael M and Edwards, Christine and Grossen, Christine and Kardos, Marty and Laikre, Linda and Ramakrishnan, Uma} } @article {160477, title = {Conservation: Sequencing and saving the Saola?}, journal = {Curr Biol}, volume = {35}, year = {2025}, month = {2025 Sep 22}, pages = {R878-R880}, abstract = {

The Critically Endangered Saola is a unique and cryptic Asian member of the cattle family. A new study analyses its genome, identifying evolutionary affinities, genetic variation and a possible path for conservation through captive breeding. But saving the Saola from extinction will require much more.

}, keywords = {Animals, Cattle, Conservation of Natural Resources, Endangered Species, Genetic Variation, Genome}, issn = {1879-0445}, doi = {10.1016/j.cub.2025.07.086}, author = {Ramakrishnan, Uma} } @article {158507, title = {Conserved biochemical activity and function of phosphatidylinositol 5 phosphate 4 kinase regulates growth \& development}, year = {2025}, abstract = {

Co-ordination of function between multiple cells, mediated by hormones or growth factors, is a critical requirement for multi-cellularity. Phosphoinositides, generated by lipid kinase activity, are second messengers that mediate such signalling. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is a lipid kinase that phosphorylates phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. A comprehensive bioinformatics analysis of the tree of life, revealed that PIP4K is a metazoan-specific enzyme, but with homologs in choanoflagellates. We find that PIP4K from the sponge\ Amphimedon queenslandica\ (AqPIP4K), regarded as the earliest evolved metazoan, shows biochemical activity highly conserved with human PIP4K. Further, AqPIP4K was able to rescue the reduced cell size, growth and development of a\ Drosophila\ PIP4K mutant. These phenotypes are regulated through activity of the insulin receptor, a member of the receptor tyrosine kinase family, that is unique to metazoans. Overall, our work defines PIP4K as part of a signal transduction motif required to regulate receptor tyrosine kinase signalling for intercellular communication in the earliest forms of metazoans.

}, keywords = {Amphimedon queenslandica, Drosophila melanogaster, Growth and development, Insulin signalling, Lipid kinase}, doi = {https://doi.org/10.1242/jcs.263881}, url = {https://journals.biologists.com/jcs/article-abstract/doi/10.1242/jcs.263881/368299/Conserved-biochemical-activity-and-function-of?redirectedFrom=PDF}, author = {Krishnan, H and Muzaffar, S and Sharma, S and Ramya, V and Ghosh, A and Sowdhamini, R and Padinjat, R} } @article {158516, title = {Correlates of Tree Cavity Presence in a Tropical Deciduous Forest of the Northern Western Ghats, India}, year = {2025}, abstract = {

Close to 18\% of the global avifauna require tree cavities for breeding and roosting. Cavities are therefore a critical resource for birds, and an understanding of its dynamics is vital to safeguard populations of cavity-users vis-{\`a}-vis forest management practices. Only a small proportion of trees in an ecosystem host this resource, and the likelihood of cavity presence on a tree may depend on how suitable its wood is for cavity formation, particularly through excavation by birds such as woodpeckers. Such understanding of which trees are more likely to host cavities than others is still lacking in the global tropics. To develop a baseline understanding of cavity resource dynamics in the Indian tropics, we estimated cavity abundance in a dry deciduous forest ecosystem in the northernmost Western Ghats, India, and investigated the ecological correlates of cavity occurrence. We recorded cavities only on trees with girth (GBH) greater than 80 cm, and limited our analyses to such trees. We found that 6.4\% of 843 trees harboured cavities, and that 48\% of all cavities were excavated. The study area contained a mean of 5.4 (95\%CI 3.50{\textendash}7.50) cavity trees, and 10.3 cavities (95\%CI 8.60{\textendash}12.20) per hectare. Species like Indian Rosewood\ Dalbergia latifolia\ and Teak\ Tectona grandis\ that are moderately hard-wooded were more likely to harbour cavities than the especially hard-wooded\ Terminalia crenulata, or soft-wooded species. We also found that trees with larger girth hosted cavities more often than smaller trees, with the relationship particularly strong in Teak. Our study suggests that prioritizing the preservation of large trees and cavity-associated tree species can aid in safeguarding cavities as a resource in such landscapes.

}, doi = {https://doi.org/10.3161/00016454AO2024.59.2.006}, url = {https://bioone.org/journals/acta-ornithologica/volume-59/issue-2/00016454AO2024.59.2.006/Correlates-of-Tree-Cavity-Presence-in-a-Tropical-Deciduous-Forest/10.3161/00016454AO2024.59.2.006.full$\#$:~:text=We\%20found\%20that\%206.4\%25\%20of,8.60\%E2\%80\%9312.20)\%20p}, author = {Muhammedmaaz S. Mukardamwala and Pranav G. Trivedi and Dhawal Mehta and Ashwin Viswanathan} } @article {160482, title = {Coupling between spatial compartments integrates morphogenetic patterning in the organ of Corti.}, journal = {PLoS Biol}, volume = {23}, year = {2025}, month = {2025 Sep}, pages = {e3003350}, abstract = {

Morphogenetic information arises from a combination of genetically encoded cellular properties and emergent cellular behaviors. The spatio-temporal implementation of this information is critical to ensure robust, reproducible tissue shapes, yet the principles underlying its organization remain unknown. We investigated this principle using the mouse auditory epithelium, the organ of Corti (OC). OC consists of a sensory domain, which transduces sound through polar mechanosensory hair cells (HC), part of a mosaic with supporting cells (SC). On either side of the sensory domain are non-sensory domains. These domains undergo cellular rearrangements, which, together, lead to a spiral cochlea that contains planar polarized HCs. This makes the mammalian cochlea a compelling system to understand coordination across spatial scales. Using genetic and ex vivo approaches, we found patterning of OC into sensory and non-sensory domains is associated with a combinatorial expression of adhesion molecules, which underpins OC into spatially defined compartments, enabling planar cell polarity (PCP) cues to regulate compartment-specific organization. Through compartment-specific knockouts of the PCP protein, Vangl2, we find evidence of compartment coupling, a non-linear influence on the organization within one compartment when cellular organization is disrupted in another. In the OC, compartment coupling originates from vinculin-dependent junctional mechanics, coordinating cellular dynamics across spatial scales.

}, keywords = {Animals, Body Patterning, Cell Polarity, Hair Cells, Auditory, Mice, Mice, Knockout, Morphogenesis, Nerve Tissue Proteins, Organ of Corti}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3003350}, author = {Prakash, Anubhav and Raman, Sukanya and Kaushik, Raman and Manchanda, Pallavi and Iyer, Anton S and Ladher, Raj K} } @article {158504, title = {Cryo-EM structures of Mycobacterium tuberculosis imidazole glycerol phosphate dehydratase in the apo state and in the presence of small molecules.}, year = {2025}, abstract = {

Unlike humans,\ Mycobacterium tuberculosis\ (Mtb), the causative agent of human tuberculosis, has a\ de novo\ histidine-biosynthesis pathway. The enzyme imidazole glycerol phosphate dehydratase (IGPD), which catalyses the conversion of imidazole glycerol phosphate to imidazole acetol phosphate, has been studied extensively from various organisms and has become a major target for the development of antibacterial, antiweed and antifungal small molecules. In our previous studies, we have shown that in crystals IGPD forms a 24-mer oligomeric state in which the monomers are arranged in 432 symmetry. In order to gain insights into the oligomeric state of\ Mtb\ IGPD in solution, we determined cryogenic sample electron microscopy (cryo-EM) structures of apo IGPD at 2.2 and 3.1 {\r A} resolution. In addition, we also determined the cryo-EM structure of IGPD in the presence of 3-amino-1,2,4-triazole (ATZ) to 2.8 {\r A} resolution. The results of this work, which corroborate those from the crystallographic studies, indicate that IGPD forms a homo-oligomeric structure in solution comprising of 24 subunits. ATZ binds in the active-site pocket of the enzyme, which is located at the interface of three monomers and tethers 24 ATZ molecules. The results of this study suggest that cryo-EM, in addition to being a rapidly evolving and complementary imaging technology for elucidating 3D structures of biological macromolecules, can be useful in pinpointing the mode of binding small molecules of low mass (here \~{}85 Da) and mapping protein-ligand interactions, which could assist in the design of accurate (high-potency) inhibitors.

}, keywords = {cryo-EM; tuberculosis; histidine-biosynthesis pathway; imidazole glycerol phosphate dehydratase; drug discovery.}, doi = {https://doi.org/10.1107/S2053230X25004595}, url = {https://scripts.iucr.org/cgi-bin/paper?buy=yes\&cnor=ih5008\&showscheme=yes\&sing=yes}, author = {Raina, R and Kar, D and Singla, M and Tiwari, S and Kumari, S and Aneja, S and Kumar, V and Banerjee, S and Goyal, S and Pal, RK and Vinothkumar, KR and Biswal, B} } @article {158494, title = {Decadal scale fire dynamics in savannas and forests of the Nilgiri Biosphere Reserve, India}, year = {2025}, abstract = {
Background

The Nilgiri Biosphere Reserve (NBR) in the Western Ghats, India, contains a mosaic of savannas and forests. This landscape experiences wildfires regularly, but we lack an understanding of factors driving fire regimes in the region.

Aims

To examine the effects of climate, vegetation and human activity on wildfires in the NBR.

Methods

Using remotely sensed datasets, we examine how mean annual rainfall (MAR), topographic complexity and human activity influence fires in savannas and forests of the NBR across a wet (2001{\textendash}2010) and dry decade (2011{\textendash}2020).

Key results

Across both decades, savannas burned more frequently and over larger areas than forests. Burnt area and fire frequency in both habitats were higher in the wet decade. Human modification was the major driver of fire occurrence in the wet decade, but MAR took on greater importance in the dry decade.

Conclusions

Savannas and forests in the NBR have differing fire regimes. During dry periods, these systems are fuel limited and MAR best describes the occurrence of fires. During wet periods when fuel is not limiting, proxies for anthropogenic ignitions best explain fire occurrence.

Implications

Climate, vegetation and humans collectively determine fire regimes in the NBR. Fire management must integrate across all these factors at the landscape scale to be effective.

}, keywords = {fire management, Forests, savannas, Southern India, traditional burning practices, Western Ghats.}, doi = {doi.org/10.1071/WF24174 }, url = {https://www.publish.csiro.au/WF/WF24174 }, author = {Pradyumna Rajashekar and Aparna Krishnan and Varun Varma and Jayashree Ratnam and Mahesh Sankaran and Caroline E. R. Lehmann} } @article {157498, title = {Differential impacts of grazing on grassland plant diversity, biomass, soil C, and soil N across an elevation gradient}, journal = {Ecological Applications}, year = {2025}, month = {28 April 2025}, type = {Research Article}, abstract = {

Understanding how vegetation traits and soil characteristics respond to grazing in grasslands is fundamental to their restoration and management. Here, we investigated changes in species diversity, plant productivity, soil total nitrogen (STN), and soil organic carbon (SOC) storage following grazer exclusion at three grassland sites along an elevation gradient in the Kashmir Himalaya. Plant cover, aboveground and belowground biomass (AGB and BGB, respectively), SOC, and STN increased following six years of grazing exclusion, though species diversity indices declined over this period. Grazer exclusion increased the biomass of all functional groups (sedges, grasses, legumes, and forbs), with sedges, particularly\ Carex muricata, showing the highest increase. Grazer effects on AGB and BGB, SOC, and STN varied with elevation, with the most pronounced effect of grazing detected at the highest elevation site. Grazer effects on the vertical distribution of root biomass, SOC, and STN were restricted to topsoil (10 cm) at low-elevation sites but extended to deeper layers of soil at high-elevation sites.

}, doi = {https://doi.org/10.1002/eap.70031}, url = {https://esajournals.onlinelibrary.wiley.com/doi/10.1002/eap.70031?af=R}, author = {Ishrat Shaheen and Rayees A. Malik and Mahesh Sankaran and Manzoor A. Shah} } @article {153341, title = {Discriminating neural ensemble patterns through dendritic computations in randomly connected feedforward networks.}, journal = {Elife}, volume = {13}, year = {2025}, month = {2025 Jan 24}, abstract = {

Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.

}, keywords = {Animals, Axons, Computer Simulation, Dendrites, Hippocampus, Models, Neurological, Nerve Net, Neurons, Rats, Synapses}, issn = {2050-084X}, doi = {10.7554/eLife.100664}, author = {Bhanu Priya Somashekar and Upinder Singh Bhalla} } @article {160484, title = {Distinct Chemical Cues Reprogram Cellular and Multicellular Phenotypes in Ovarian Cancer Spheroids.}, journal = {Small}, year = {2025}, month = {2025 Sep 16}, pages = {e06120}, abstract = {

The self-organization of cellular collectives is crucial in development and cancer. Multicellular aggregation in cancer is associated with a higher efficiency of metastasis. However, it is not fully understood how mechanochemical microenvironmental cues affect the organization and stability of such ensembles. Here, using a model system of ovarian cancer spheroids, which temporally transit from solid, dysmorphic moruloids to structurally plastic, lumen-containing blastuloids, it is shown that the periodic volume fluctuations observed in blastuloids are driven by lumenal fluid influx and cell-cell junctional states. Furthermore, blastuloid cell states are reprogrammed, which enables them to rapidly recover from even complete structural disintegration and self-organize into fully lumenized ensembles. Using targeted chemical perturbations, two distinct cues are identified that regulate separate transition traits: calcium levels establish cell states cognate to, and pH regulates the fluctuation dynamics of blastuloid phenotypes. The work holds significant implications toward understanding mechanisms governing structural resilience and plasticity in complex cellular assemblies.

}, issn = {1613-6829}, doi = {10.1002/smll.202506120}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Langthasa, Jimpi and Bhat, Ramray and Bhattacharjee, Tapomoy} } @article {159720, title = {Distinct filament morphology and membrane tethering features of the dual FtsZ paralogs in Odinarchaeota.}, journal = {EMBO J}, year = {2025}, month = {2025 Aug 08}, abstract = {

The Asgard phylum has emerged as a model to study eukaryogenesis because of their close relatedness with the eukaryotes. In this study, we use FtsZ proteins from a member of the class Odinarchaeia as representatives to investigate the probable origin, evolution, and assembly of the FtsZ/tubulin protein superfamily in Asgard archaea. We performed a comparative analysis of the biochemical properties and cytoskeletal assembly of FtsZ1 and FtsZ2, the two FtsZ isoforms in the Odinarchaeota metagenome. Our electron microscopy analysis reveals that OdinFtsZ1 assembles into curved single protofilaments, while OdinFtsZ2 forms stacked spiral ring-like structures. Upon sequence analysis, we identified an N-terminal amphipathic helix in OdinFtsZ1, which mediates direct membrane tethering. In contrast, OdinFtsZ2 is recruited to the membrane by the anchor OdinSepF via OdinFtsZ2{\textquoteright}s C-terminal tail. Overall, we report the presence of two distant evolutionary paralogs of FtsZ in Odinarchaeota, with distinct filament assemblies and differing modes of membrane targeting. Our findings highlight the diversity of FtsZ proteins in the archaeal phylum Asgardarchaeota, providing valuable insights into the evolution and differentiation of tubulin-family proteins.

}, issn = {1460-2075}, doi = {10.1038/s44318-025-00529-7}, author = {Kumari, Jayanti and Uthaman, Akhilesh and Bose, Sucharita and Kundu, Ananya and Sharma, Vaibhav and Dutta, Soumyajit and Dhar, Anubhav and Roy, Srijita and Srinivasan, Ramanujam and Pande, Samay and Vinothkumar, Kutti R and Gayathri, Pananghat and Palani, Saravanan} } @article {155514, title = {DNA barcodes narrow down the possible sources of introductions of an invasive banana skipper, Erionota torus Evans (Lepidoptera, Hesperiidae)}, journal = {CABI Agriculture and Bioscience}, volume = {6}, year = {2025}, month = {27 February 2025}, abstract = {

The banana skipper,\ Erionota torus\ Evans (Lepidoptera, Hesperiidae, Hesperiinae, Erionotini) is a South-east Asian pest of banana that, in the last 60 years, has spread to the southern Philippines, Taiwan, Japan, India, Sri Lanka, Mauritius and La R{\'e}union, and potentially threatens Africa and Tropical America. A partial library of DNA barcodes from the indigenous and introduced ranges was built. Based on our analysis, the indigenous populations can be divided into an {\textquoteleft}East{\textquoteright} group, in China and Vietnam, and a {\textquoteleft}West{\textquoteright} group in India, Nepal, Myanmar and west Malaysia. Further, within the {\textquoteleft}West{\textquoteright} group, there is a coherent {\textquoteleft}Malaysia{\textquoteright} subgroup from west Malaysia. Introduced populations in south India, La R{\'e}union and Taiwan showed almost no variation in barcodes, suggesting they are each based on a single homogenous introduction. We conclude that the introduced populations in Taiwan and Japan match the {\textquoteleft}East{\textquoteright} group, the introduced populations in Mauritius and La R{\'e}union match the {\textquoteleft}Malaysia{\textquoteright} subgroup and the introduced population in south India matches the {\textquoteleft}West{\textquoteright} group. These results are discussed in the context of existing ideas regarding the source of each introduction, and the implications in terms of pathways of entry.

}, doi = {https://doi.org/10.1079/ab.2025.0016}, url = {https://www.cabidigitallibrary.org/doi/10.1079/ab.2025.0016}, author = {Matthew J.W. Cock and Alan G. Buddie and Giovanni Cafa and Hideyuki Chiba and Athulya Girish Kizhakke and Hsu Yu-Feng and Krushnamegh Kunte} } @article {152904, title = {Is Drosophila Larval Competition Involved in Incipient Speciation?}, journal = {J Chem Ecol}, volume = {51}, year = {2025}, month = {2025 Jan 22}, pages = {2}, abstract = {

Geographical, ethological, temporal and ecological barriers can affect interbreeding between populations deriving from an ancestral population, this progressively leading to speciation. A rare case of incipient speciation currently occurs between Drosophila melanogaster populations sampled in Zimbabwe (Z) and all other populations (M). This phenomenon was initially characterized by Z females refusing to mate with M males. Despite the fact that Z and M flies produce different amounts of cuticular pheromones, their manipulation and that of other sensory signals exchanged during courtship behavior only marginally rescued the behavioral isolation. To further explore the putative mechanisms involved in this phenomenon, we first assessed the fecundity in matings between Z and M flies. Then, we measured the reproduction and survival in adults resulting of co-cultured Z and M larvae. In these two experiments, Z flies rarely emerged. Z and M larvae produced different amounts of food-derived metabolites which were altered in co-culture condition. This maybe related to the different bacteria composition in the gut and body of Z and M flies. However, the mating behavior of co-cultured flies did not change and their cuticular pheromone profile was slightly altered. Thus, the Z/M larval competition could reinforce the barriers induced by gametic and behavioral isolation processes on this incipient speciation phenomenon.

}, keywords = {Animals, Competitive Behavior, Drosophila melanogaster, Female, Fertility, Genetic Speciation, Larva, Male, Pheromones, Reproduction, Sexual Behavior, Animal}, issn = {1573-1561}, doi = {10.1007/s10886-025-01560-y}, author = {Jean-Fran{\c c}ois, Ferveur and Pratibha, Sanjenbam and Baptiste, Regnier and Jean-Pierre, Farine and J{\'e}r{\^o}me, Cortot and Deepa, Agashe and Claude, Everaerts} } @article {158517, title = {The dynamics of cave roost use by bats in the central Himalayas of Nepal: implications for conservation}, year = {2025}, abstract = {

The seasonal use of caves by bats can be attributed to physiologically demanding activities like mating and reproduction in spring and torpor in winter. Cave use, however, varies within and across species and can depend on the physical and microclimatic conditions of the caves. Understanding the current patterns and predictors of cave use is therefore crucial to develop a reference for assessing the response of bats to future changes in climatic conditions. We quantified the diversity and abundance of bats in 41 caves that varied in structure and temperature across a seasonal (mid-winter, late-winter and early-spring) and an elevational (400{\textendash}2700 m above sea level) gradient in the central Himalayas. Richness and abundance of bat species exhibited seasonal variation, with more species and individuals present in caves during early-spring (n = 15) compared to mid-winter (n = 9). Species richness declined linearly with elevation in mid-winter but remained relatively similar until 900 msl and then declined in late-winter and early-spring. Species such as\ Hipposideros armiger\ (20.14 {\textpm} 1.60{\textdegree}C in spring and 17.97 {\textpm} 0.88{\textdegree}C in mid-winter),\ Rhinolophus affinis\ (19.98 {\textpm} 1.76{\textdegree}C in spring and 16.18 {\textpm} 3.09{\textdegree}C in mid-winter) and\ Rhinolophus cf. pusillus\ (19.55 {\textpm} 1.64{\textdegree}C in spring and 15.43 {\textpm} 2.87{\textdegree}C in mid-winter) preferred warmer microclimates within caves during early-spring compared to mid-winter. The season- and species-specific cave use that we report here suggests that even minor fluctuations in cave temperatures could potentially alter the composition of bat communities inside caves. Prioritization assessment based on a bat cave vulnerability index indicates that different caves must be protected based on their specific usage patterns and the abundance of species they support at various times. Overall, we highlight the importance of studying cave-dwelling bats in climate-vulnerable areas such as the Himalayas where species richness is high to help understand and predict the responses of animals to climate change.

}, keywords = {Chiroptera, Climate Change, community structure, elevation, roost use, Seasons}, doi = {https://doi.org/10.1111/jzo.70018}, url = {https://zslpublications.onlinelibrary.wiley.com/doi/10.1111/jzo.70018?af=R}, author = {S. Baniya and K. Neupane, M and Thaker, V. R and Goswami and V. Ramachandran} } @article {161986, title = {Ecological Risk-Benefit Analysis for Assisted Colonization.}, journal = {Glob Chang Biol}, volume = {31}, year = {2025}, month = {2025 Nov}, pages = {e70613}, abstract = {

Assisted colonization (AC), translocating a species outside its indigenous range to avoid its extinction, is one of the few conservation options for some species. It is also controversial because of the history of ecological impacts of invasive species, including the extinction of native species as a result of novel ecological interactions resulting from the introduction. Although several national and international organizations have issued guidelines related to AC, none allow case-specific decision-making based on risks and benefits to biodiversity. We propose a two-pronged approach to fill this gap. The first step aims to separate clear-cut cases of AC from those that require an in-depth risk analysis. We propose a set of seven qualitative criteria to identify AC projects that are clearly low-risk and high-benefit, and therefore should not be controversial, and those that are clearly high-risk or low-benefit and therefore should not be attempted. This identifies only the most obvious cases, leaving out many cases to be determined through a quantitative analysis to estimate the probabilities of extirpation of the resident species because of AC, which is the second step of our approach. We propose a roadmap for developing such a system based on community ecology theory, and a framework for considering the estimated probabilities in a global context. Our framework recommends an AC project only if it would result in a larger number of globally extant species than a scenario of no action. We propose large-scale testing of the clear-cut approach, further development of the quantitative approach, and wide consultation for adopting international guidelines for risk assessment of AC projects.

}, keywords = {Biodiversity, Conservation of Natural Resources, Ecosystem, Extinction, Biological, Introduced Species, Risk Assessment}, issn = {1365-2486}, doi = {10.1111/gcb.70613}, author = {D{\textquoteright}Andrea, Rafael and Barab{\'a}s, Gy{\"o}rgy and Dalrymple, Sarah E and Foden, Wendy and Genovesi, Piero and Krishnadas, Meghna and Leibold, Mathew A and McPeek, Mark A and Moehrenschlager, Axel and Rodriguez, Jon Paul and Ak{\c c}akaya, H Re{\c s}it} } @article {155512, title = {Editorial: Biotropica Announces a New Paper Category: Synthesis}, year = {2025}, abstract = {

What does it take to tackle big questions in ecology, evolution, and conservation that do not have quick answers? Several important tools have emerged in recent years including literature synthesis and meta-analysis (Halpern et\ al.\ 2023; Lortie\ 2014), complemented by distributed network experiments (Powers et\ al.\ 2009; Roslin et\ al.\ 2017). Synthesis often consists of meta-analyses and data integration, wherein researchers compile and analyze data from multiple sources in the literature. Often, these studies integrate information from multiple spatial sources and yield inferences at continental or global scales. The success of this approach is underscored by the creation of centers for ecological synthesis, such as the National Center for Ecological Analysis and Synthesis (NCEAS) in the United States or the Synthesis Centre for Biodiversity Sciences in Germany (sDiv). In parallel, other research groups have developed distributed ecological networks of experiments and/or observations, for example, NutNet or DarkDivNet (Borer et\ al.\ 2014; P{\"a}rtel et\ al.\ 2025). In these projects, researchers focus on different locations, but they all implement standardized methods to yield geographically comparative data. These approaches have undoubtedly contributed to our understanding of ecological patterns and processes at broad spatial scales, and yet they are not the only method of synthesis. The nature of tropical ecological research often means that some researchers and research groups return to the same study location year after year, building programs of investigation over decades that may integrate the role of fluctuating environmental conditions in their study system. This approach chips away at big questions one paper at a time and yields major results when synthesized (e.g., Melin et\ al.\ 2020).

Meta-analyses or literature reviews typically begin with database searches, such as Google Scholar or Web of Science, and discourage {\textquotedblleft}excessive{\textquotedblright} self-citation, as the objective is to derive generalizable patterns across many published studies. While global syntheses have provided broad ecological insights, this may have cost us the types of ecological insights that come from {\textquotedblleft}slow ecology{\textquotedblright} focused on a deeper understanding of a single study system at one location (Billick and Price\ 2010). Such studies, with the deep glimpses they provide into the natural history of an ecosystem, are often the source of novel observations and mechanistic understanding in ecology. They are also critical for conservation and management that require local action. We contend that we lack a platform that encourages groups of investigators to synthesize and integrate their findings from a concerted and coordinated program of study conducted in a single place over decades, that is, papers where the goal is to trace the arc of a research program over many years through {\textquotedblleft}self-citation{\textquotedblright}. To fill this gap, Biotropica is creating a new paper category called {\textquotedblleft}Synthesis{\textquotedblright}. The aim is not for authors to present a typical {\textquotedblleft}Review Article{\textquotedblright} or meta-analysis. The new Biotropica Synthesis papers will be distinguished by being deep in time and site-specific, celebrating the insights that emerge from local, place-based ecology and showing a profound understanding of the site{\textquoteright}s natural history over a concerted period of time.

How will Synthesis papers work? Synthesis papers will follow the same format as {\textquotedblleft}Reviews{\textquotedblright}, that is, 8000 word limit (excluding references). As the emphasis is on understanding the insights from a research group{\textquoteright}s work, extensive self-citations are acceptable and, indeed, expected. However, in contrast to Biotropica{\textquoteright}s Review paper category, Synthesis papers will be solicited by invitation, referral, or self-referral. The authors of all Synthesis papers are requested to send a brief inquiry email before submission to the Editorial Office that details: the location of the research, the topics or ideas addressed by the research program, the number of years of work that will be synthesized (i.e., we expect 10 years at least), a list of the major publications that will be discussed and a list of potential co-authors that would ideally include graduate students, postdoctoral research associates, and research assistants. If locally based field assistants have made substantial contributions to the work presented in the Synthesis, we strongly recommend authors consider whether their contributions merit co-authorship (see Ram{\'\i}rez-Castaneda et\ al.\ 2022). Last, the inquiry should include a couple of sentences on how synthesizing this research program will provide new insights that will be of interest to tropical ecologists, that is, Biotropica readers. The Biotropica Editorial Office will then provide feedback and encourage or discourage a full submission that will be subjected to our standard peer review processes (i.e., submission does not guarantee acceptance). As Synthesis represents a new paper category for Biotropica, we do not yet have a collection of examples to use as guidelines. However, we point potential Synthesis authors to an excellent review paper that exemplifies the goals of this new paper category entitled {\textquotedblleft}Primate life history, social dynamics, ecology, and conservation: Contributions from long-term research in {\'A}rea de Conservaci{\'o}n Guanacaste, Costa Rica{\textquotedblright} by Melin et\ al.\ (2020). We look forward to receiving your contributions and hope that this new paper category spurs integration and reflection, and also serves to identify future research directions{\textemdash}all of which are necessary to make progress toward answering the big questions in ecology and conservation.

}, doi = { https://doi.org/10.1111/btp.70020}, url = {https://onlinelibrary.wiley.com/doi/10.1111/btp.70020}, author = {Jennifer S. Powers and Francis Q. Brearley and Jayashree Ratnam and Eleanor M. Slade} } @article {159713, title = {Effects of sampling methodology on phenology indices: Insights from sites across India and modelling.}, journal = {J Biosci}, volume = {50}, year = {2025}, month = {2025}, abstract = {

Plant phenology is the study of the timing and extent of leaf, flower, and fruit production. Phenology data are used to study the drivers of cyclicity and seasonality of plant life-history stages, interactions with organisms such as pollinators, and effects of global change factors. Indices such as the timing of phenological events, and the proportion of individuals in a particular phenophase, seasonality, and synchrony have often been used to summarise plant phenology data. However, these indices have specific utilities and limitations and may be sensitive to sampling methodology, making cross-site comparisons challenging, particularly when data collection methods vary in terms of sample size, observation frequency, and the resolution at which phenophase intensity scores/values are recorded. We used fruiting phenology data from tropical trees across five sites in India to study the effects of sampling methodology on two indices: population-level synchrony (overlap) and seasonality. We supplemented these results with simulations of fast- and slow-changing phenologies to test for the effects of sampling methodology on these indices. We found that the overlap index is sensitive to the resolution of phenophase intensity measurement, with coarser intensity measures leading to overestimation of the overlap index. The seasonality index, on the other hand, was not affected by intensity resolution. Simulations indicated that finer intensity resolution is more important than frequency of observation to accurately estimate population synchrony and seasonality for fast- and slow-changing phenophases. Based on our findings, we provide recommendations for future study designs of tropical tree phenology research, particularly for long-term or cross-site studies.

}, keywords = {Flowers, Fruit, India, Plant Leaves, Pollination, Seasons, Trees}, issn = {0973-7138}, author = {Tiruvaimozhi, Yadugiri V and Teegalapalli, Karthik and Reddy, Abinand and Murali, Akhil and Datta, Aparajita and Krishnan, Aparna and Ratnam, Jayashree and Sankaran, Mahesh and Ongole, Shasank and Kasinathan, Srinivasan and Raman, T R Shankar and Ramaswami, Geetha} } @article {155511, title = {Encoding of antennal position and velocity by the Johnston{\textquoteright}s organ in hawkmoths.}, journal = {J Exp Biol}, year = {2025}, month = {2025 Mar 18}, abstract = {

Insect antennae function as versatile, multimodal sensory probes in diverse behavioural contexts. In addition to their primary role as olfactory organs, they serve essential mechanosensory functions across insects, including auditory perception, vestibular feedback, airflow detection, gravity sensing, and tactile sensation. These diverse functions are facilitated by the mechanosensory Johnston{\textquoteright}s organ (JO), located at the joint between the flagellum and the second antennal segment i.e. the pedicel. The pedicel-flagellum joint lacks muscles which means that the Johnston{\textquoteright}s organs can perceive only passive deflections of the flagellum. Earlier work which characterized the sensitivity and short response time of the sensory units of JO in hawkmoths, showed that their sensitivity to a broad frequency range is range-fractionated. This vastly expands the functional repertoire of the JO. However, it is not clear what components of antennal kinematics are encoded by the JO. Here, we conducted experiments to test the hypothesis that JO neurons encode the position and velocity of angular movements of the flagellum. We recorded intracellularly from the axons of primary sensory neurons of JO while stimulating it with ramp-and-hold stimuli in which either the antennal position or the antennal angular velocity was maintained at various constant values. Our study shows that JO neurons encode angular velocity and position of the antenna in their response. We also characterized the neural adaptation of the responses to angular velocities and positions. A majority of neurons were sensitive to a movement in the ventrad direction, in the direction of gravity. The adaptation and the directional response properties give rise to a nonlinear hysteresis-like response. Together, these findings highlight the neurophysiological basis underlying the functional versatility of the JO.

}, keywords = {Daphnis nerii; Adaptation; Hawkmoths; Hysteresis; Johnston{\textquoteright}s organ; Mechanosensors; Neurophysiology; Sensory encoding.}, issn = {1477-9145}, doi = {10.1242/jeb.249342}, url = {https://pubmed.ncbi.nlm.nih.gov/40099381/}, author = {Mukunda, Chinmayee L and Sane, Sanjay P} } @article {161978, title = {Enhanced Notch dependent gliogenesis and delayed physiological maturation underlie neurodevelopmental defects in Lowe syndrome.}, journal = {EMBO Mol Med}, year = {2025}, month = {2025 Nov 11}, abstract = {

Coordination of cellular and physiological development by signaling is required for normal brain structure and function. Mutations in OCRL, a phosphatidylinositol 4,5 bisphosphate [PI(4,5)P], 5-phosphatase leads to Lowe Syndrome (LS). However, the mechanism by which mutations in OCRL leads to the neurodevelopmental phenotypes of LS is not understood. We find that on differentiation of LS patient iPSC, neural cultures show reduced excitability and enhanced GFAP levels. Multiomic single-nucleus RNA and ATACseq analysis of neural stem cells revealed enhanced numbers of cells with a gliogenic cell state. Analysis of snRNA seq revealed increased levels of DLK1, a Notch ligand in LS patient NSC associated increased levels of cleaved Notch and elevation of its transcriptional target HES5, indicating upregulated Notch signaling. Treatment of iPSC derived brain organoid with an inhibitor of PIP5K, the lipid kinase that synthesizes PI(4,5)P, was able to restore neuronal excitability and rescue Notch signaling defects in OCRL deficient organoids. Overall, our results demonstrate a role for PI(4,5)P dependent regulation of Notch signaling, cell fate specification and neuronal excitability regulated by OCRL.

}, issn = {1757-4684}, doi = {10.1038/s44321-025-00327-y}, author = {Sharma, Yojet and Bhatia, Priyanka and Rangappa, Gagana and Saha, Sankhanil and Raghu, Padinjat} } @article {160483, title = {Epithelial fusion is mediated by a partial epithelial-mesenchymal transition.}, journal = {Biol Open}, volume = {14}, year = {2025}, month = {2025 Sep 15}, abstract = {

Epithelial fusion is a fundamental morphogenetic process critical for the closure and compartmentalisation of developing organs. While widely studied in systems such as neural tube and palatal closure, the cellular transitions that enable fusion remain poorly understood. Here, we investigate epithelial fusion during chick otic vesicle closure and identify a transient population of cells at the epithelial interface that mediate this process. These otic epithelial edge (OE) cells exhibit distinct morphology, reduced apicobasal polarity, and dynamic junctional remodelling, including altered distribution of ZO-1, CDH1 and RAC1. Notably, OE cells lack basal contact and display high sphericity, consistent with a partial epithelial-to-mesenchymal transition (EMT) phenotype. Transcriptomic profiling of microdissected tissues reveals that OE cells constitute a transcriptionally distinct population, enriched for EMT regulators, extracellular matrix remodelling genes, and WNT pathway components. Among these, the transcription factors Grhl2 and Sp8 were specifically expressed at the OE and exhibited opposing roles in epithelial identity. CRISPR-Cas9-mediated knockdown of either gene led to disrupted CDH1 localisation, loss of OE cell morphology and failure in epithelial segregation. These results suggest that epithelial fusion requires a regulated, hybrid EMT state that balances junctional plasticity with tissue cohesion. Our findings demonstrate that fusion-competent epithelial cells are not merely passive participants but actively modulate their shape, polarity, adhesion and genetic identity to enable morphogenesis.

}, keywords = {Animals, Chick Embryo, Epithelial Cells, Epithelial-Mesenchymal Transition, Gene Expression Profiling, Gene Expression Regulation, Developmental, Morphogenesis, Transcription Factors}, issn = {2046-6390}, doi = {10.1242/bio.062213}, author = {Tamilkumar, Varsha N and Purushothama, Harsha and Ladher, Raj K} } @article {160481, title = {The evolution of function in the DNA binding domain of the CRP/FNR family.}, journal = {Genome Biol Evol}, year = {2025}, month = {2025 Sep 25}, abstract = {

Transcriptional regulation, facilitated by transcription factors (TFs), contributes to bacterial response to environmental and cellular perturbations. How have TFs diversified and gained their functions? We use the CRP/FNR family to study this question across \~{}6000 prokaryotic genomes. Characterized by homology to TFs CRP (cyclic AMP Receptor Protein) and FNR (Regulator of Fumarate and Nitrate Reductase) in Escherichia coli, the two functions of this family - sequence-specific DNA binding and transcriptional activation by direct contacts to RNA polymerase - are conferred by the helix-turn-helix containing DNA binding domain. We constructed a rooted phylogeny of this domain and performed residue conservation analysis on extant and in-silico reconstructed ancestral sequences of CRP/FNR family members. Residues that confer DNA binding specificity likely emerged in the overall ancestor of the sequence family. This ancestor does not fall into classes containing either E. coli CRP (Eco-CRP) or E. coli FNR (Eco-FNR) clades, but instead a large and diverse class that we call "CRP-like". Residues key for base-specific DNA binding remain largely conserved in the family. Residues (together called AR1) which make direct contacts with αCTD of RNA Polymerase are conserved only in the Eco-CRP class and restricted to Gammaproteobacteria. The corresponding {\textquoteright}287 determinant{\textquoteright} interface on αCTD is again fully conserved only in Gammaproteobacteria, which contain Eco-CRP members, following step-wise evolution initiated at the Proteobacterial common ancestor. These suggest suggesting co-emergence of the interface residues in Eco-CRP. Our analysis hence shows that Class I transcriptional activation through AR1 on CRP and the determinant of αCTD, as described in E. coli CRP, is phylogenetically restricted, while base-specific DNA binding has been present in the CRP/FNR family throughout its evolutionary history.

}, issn = {1759-6653}, doi = {10.1093/gbe/evaf182}, author = {Krishnaswamy, Madhumitha and Seshasayee, Aswin Sai Narain} } @article {157490, title = {The Evolution of Sequence Specificity in a DNA Binding Protein Family.}, journal = {J Mol Biol}, volume = {437}, year = {2025}, month = {2025 Jul 15}, pages = {169177}, abstract = {

Transcriptional regulation enables bacteria to adjust to its environment. This is driven by transcription factors (TFs), which display DNA site recognition specificity with some flexibility built in. TFs, however, are not considered essential to a minimal cellular life. How did they evolve? It has been hypothesized that TFs evolve by gaining specificity (and other functions) on a background of non-specific chromosome structuring proteins. We used the IHF/HU family of DNA binding proteins, in which IHF binds DNA in a sequence-specific manner, whereas HU binds more indiscriminately, to test this hypothesis. We show that HUβ has been present from the bacterial root, while both IHF subunits emerged much later and diversified in Proteobacteria, with HUα having possibly arisen from transfer events in Gammaproteobacteria. By reconstructing ancestral sequences in-silico on a rooted phylogeny of IHF/HU we show that the common ancestor of this family was probably HU-like and therefore non-specific in binding DNA. IHF evolved from a branch of HU after HU had substantially diverged. Various residues characteristic of IHFα and shown to be involved in specific sequence recognition (at least in E. coli) have likely been co-opted from preexisting residues in HU, while those residues of IHFβ have likely evolved independently, suggesting that each of the IHF subunits has undergone different trajectories to acquire their DNA binding properties.

}, keywords = {HU; IHF; bacteria; evolution; transcription factor.}, issn = {1089-8638}, doi = {10.1016/j.jmb.2025.169177}, url = {https://www.sciencedirect.com/science/article/pii/S0022283625002438?via\%3Dihub}, author = {Nandy, Meghna and Krishnaswamy, Madhumitha and Sharda, Mohak and Seshasayee, Aswin Sai Narain} } @article {153342, title = {Evolution of transcription factor-containing superfamilies in Eukaryotes.}, journal = {Journal of Molecular Biology}, year = {2025}, month = {2025 Jan 23}, pages = {168959}, abstract = {

Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.

}, keywords = {DNA-binding domains; Transcription Factor; Transcription Factor evolution.}, issn = {1089-8638}, doi = {10.1016/j.jmb.2025.168959}, author = {Akshara Dubey and Ganesh Muthu and Aswin Sai Narain Seshasayee} } @article {161128, title = {Exceedingly low genetic diversity in snow leopards due to persistently small population size.}, journal = {Proc Natl Acad Sci U S A}, volume = {122}, year = {2025}, month = {2025 Oct 14}, pages = {e2502584122}, abstract = {

Snow leopards () serve as an umbrella species whose conservation benefits their high-elevation Asian habitat. Their numbers are believed to be in decline due to numerous anthropogenic threats; however, their conservation is hindered by numerous knowledge gaps. In particular, the dearth of genetic data, unique among all big cat species, hinders a full understanding of their population structure, historical population size, and current levels of genetic diversity. Here, we use whole-genome sequencing data for 41 snow leopards (37 newly sequenced) to offer insights into these unresolved aspects of snow leopard biology. Among our samples, we find evidence of a primary genetic divide between the northern and southern part of the range around the Dzungarian Basin-as previously identified using landscape models and fecal microsatellite markers-and a secondary divide south of Kyrgyzstan around the Taklamakan Desert. Most noteworthy, we find that snow leopards have the lowest genetic diversity of any big cat species, likely due to a persistently small population size throughout their evolutionary history rather than recent inbreeding. We also find that snow leopards have significantly less highly deleterious homozygous load compared to numerous species, suggesting effective purging during their evolutionary history at small population sizes. Without a large population size or ample standing genetic variation to help buffer them from any forthcoming anthropogenic challenges, snow leopard persistence may be more tenuous than currently appreciated.

}, keywords = {Animals, Conservation of Natural Resources, Ecosystem, Felidae, Genetic Variation, Microsatellite Repeats, Panthera, Population Density}, issn = {1091-6490}, doi = {10.1073/pnas.2502584122}, author = {Solari, Katherine A and Morgan, Simon and Poyarkov, Andrey D and Weckworth, Byron and Samelius, Gustaf and Sharma, Koustubh and Ostrowski, Stephane and Ramakrishnan, Uma and Kubanychbekov, Zairbek and Kachel, Shannon and Johansson, {\"O}rjan and Lkhagvajav, Purevjav and Hemmingmoore, Heather and Alexandrov, Dmitry Y and Bayaraa, Munkhtsog and Grachev, Alexey and Korablev, Miroslav P and Hernandez-Blanco, Jose A and Munkhtsog, Bariushaa and Rosenbaum, Barry and Rozhnov, Viatcheslav V and Madad Rajabi, Ali and Noori, Hafizullah and Suryawanshi, Kulbhushansingh R and Armstrong, Ellie E and Petrov, Dmitri A} } @article {154350, title = {Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance}, journal = {EMBO Reports}, year = {2025}, month = {31 January 2025}, pages = {1-21}, abstract = {

Mitochondrial DNA (mtDNA) replication is essential for mitochondrial function. This is carried out by a dedicated DNA polymerase gamma, with 5{\textquoteright}{\textendash}3{\textquoteright} polymerase and 3{\textquoteright}{\textendash}5{\textquoteright} proofreading/ exonuclease activity. Perturbations to either property can have pathological consequences. Predominant sources for replication stress are DNA lesions, such as those induced by oxidative damage. How mtDNA lesions affect the polymerase activity and mtDNA stability in vivo is not fully understood. To address this, we induce mtDNA-specific damage in\ S. cerevisiae. We observe that mtDNA damage results in significant mtDNA loss. This loss occurs independent of cell cycle progression or cell division, suggesting an active mechanism for damaged mtDNA clearance. We implicate the 3{\textquoteright}{\textendash}5{\textquoteright} exonuclease activity of the mtDNA polymerase in this clearance, with rates of loss being affected by cellular dNTP levels. Overall, our findings reveal context-dependent, selective regulation of two critical but opposing functions of polymerase gamma to ensure mitochondrial genome integrity.

}, keywords = {mtDNA Damage; PolG; Mip1; DNA Replication; Recombination \& Repair; Organelles}, issn = {1469-3178}, doi = {https://doi.org/10.1038/s44319-025-00380-1}, url = {https://www.embopress.org/doi/epdf/10.1038/s44319-025-00380-1}, author = {Akshaya Seshadri and Anjana Badrinarayanan} } @article {162675, title = {Exploration of Natural Products for Targeting IDH1/2 Mutations in Acute Myeloid Leukemia Through Ligand-Based Pharmacophore Screening, Docking, ADME-T, and Molecular Dynamic Simulation Approaches.}, journal = {Bioinform Biol Insights}, volume = {19}, year = {2025}, month = {2025}, pages = {11779322251399077}, abstract = {

BACKGROUND: Mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are prevalent drivers of acute myeloid leukemia (AML). While targeted therapies exist, resistance can emerge. This study explored the potential of natural products to identify novel dual IDH inhibitors.

METHODS: In silico screening of the COCONUT database was performed using Lipinski{\textquoteright}s Rule of Five. Pharmacophore modeling identified crucial features for IDH binding. Docking simulations with Glide (Schr{\"o}dinger) assessed binding affinity, followed by MM-GBSA calculations for free energy estimation. The most promising candidate underwent ADME/T and toxicity analysis. Finally, molecular dynamics (MD) simulations evaluated the stability of protein-ligand complexes and binding interactions, followed by trajectory analysis using dynamical cross-correlation matrix (DCCM) and principal component analysis (PCA).

RESULTS: Ternstroside D (CNP0166496) emerged as a potential dual inhibitor of IDH1 and IDH2 mutations. Docking and MM-GBSA analyses showed strong affinities with IDH1 (-14.2, -84.45 kcal/mol) and IDH2 (-16.8, -60.73 kcal/mol), exceeding those of reference inhibitors GSK321A (-9.6 kcal/mol) and Enasidenib (-8.9 kcal/mol). Key hydrogen-bond interactions with catalytic residues and stable binding during MD simulations support its dual mechanism. ADME/T predictions indicated drug-like properties and a favorable safety profile, highlighting Ternstroside D as a natural scaffold with superior binding compared with existing IDH inhibitors.

CONCLUSION: This in silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Furthermore, in vitro and in vivo studies are warranted to validate these findings.

}, issn = {1177-9322}, doi = {10.1177/11779322251399077}, author = {Das, Uddalak and Regati, Dheemanth Reddy and Kumar, Jitendra and Sowdhamini, R} } @article {160476, title = {Exploration of structural space of Cus17 lectin with glycans using molecular docking and simulation studies.}, journal = {Comput Struct Biotechnol J}, volume = {27}, year = {2025}, month = {2025}, pages = {3319-3327}, abstract = {

The Cus17 phloem protein, in the case of species, plays an important role in the phloem-based defense of the plant. Cus17 can bind to various carbohydrates present on insect exoskeletons or fungal cells. The recent experimental structure of chitotriose bound Cus17 elucidates the carbohydrate interacting residues of Cus17. Higher chito-oligosaccharides are also known to interact with Cus17, but the lack of experimental structure impedes our understanding of their interaction. In this study, we have employed methods to explore the binding interactions of higher chito-oligosaccharides with Cus17. Chitoheptaose forms stable interactions with canonical binding site residues Trp48 and Asp50. Smaller chito-oligosaccharides were observed to be relatively unstable at the canonical binding site of Cus17. Further, the chito-oligosaccharides were inspected for interactions with predicted ligand binding sites. We also generated different tetramers of Cus17 and docked the chito-oligosaccharides to the tetrameric Cus17. All chito-oligosaccharides were found to make persistent interactions with Cus17 tetramer. Interestingly, chitotriose shows the best binding affinity and maintains stable interactions with Cus17 tetramer upon extended simulations with the canonical site.

}, keywords = {Non-canonical binding; Oligosaccharides; Protein-ligand interactions}, issn = {2001-0370}, doi = {10.1016/j.csbj.2025.07.028}, author = {Tiwari, Vikas and Pathak, Aditi and Poojary, Tejaswini and Sowdhamini, Ramanathan and Surolia, Avadhesha} } @article {162687, title = {Fibrillarin regulates epithelial integrity via EZH2-mediated modulation of scribble expression.}, journal = {Cell Rep}, volume = {44}, year = {2025}, month = {2025 Nov 25}, pages = {116608}, abstract = {

Fibrillarin (FBL) is a nucleolar protein critical for rRNA biogenesis. We show that FBL is essential for the maintenance of epithelial integrity through its regulation of cell-cell adhesion proteins. RNA-seq analyses upon FBL depletion revealed deregulation of adhesion- and apical membrane organization-associated pathways. FBL loss deregulates cell polarity via increased deposition of H3K27me3 on the SCRIB promoter, driven by the localization of a subpopulation of EZH2 from the nucleolus to the nucleoplasm. Disrupting the FBL-EZH2 interaction increases cell migration, underscoring a requirement for retaining EZH2 also in the nucleolus. Furthermore, FBL depletion induces EMT in breast epithelial cells, owing to increased levels of mesenchymal factors (Snail1, Twist1, and Zeb1) and activation of Akt. Since Scribble tethers PHLPP1 and PTEN to antagonize Akt, repression of Scribble induces EMT. In summary, FBL safeguards epithelial integrity, by regulating the expression of Scribble, uncovering an FBL-EZH2 axis in EMT and metastasis.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2025.116608}, author = {Saha, Santam and A K, Balaji and Meel, Sweety and Notani, Dimple and Sengupta, Kundan} } @article {155669, title = {Forb diversity globally is harmed by nutrient enrichment but can be rescued by large mammalian herbivory}, journal = {Communications Biology}, volume = {8}, year = {2025}, month = {15 March 2025}, abstract = {

Forbs ({\textquotedblleft}wildflowers{\textquotedblright}) are important contributors to grassland biodiversity but are vulnerable to environmental changes. In a factorial experiment at 94 sites on 6 continents, we test the global generality of several broad predictions: (1) Forb cover and richness decline under nutrient enrichment, particularly nitrogen enrichment. (2) Forb cover and richness increase under herbivory by large mammals. (3) Forb richness and cover are less affected by nutrient enrichment and herbivory in more arid climates, because water limitation reduces the impacts of competition with grasses. (4) Forb families will respond differently to nutrient enrichment and mammalian herbivory due to differences in nutrient requirements. We find strong evidence for the first, partial support for the second, no support for the third, and support for the fourth prediction. Our results underscore that anthropogenic nitrogen addition is a major threat to grassland forbs, but grazing under high herbivore intensity can offset these nutrient effects.

}, doi = {https://doi.org/10.1038/s42003-025-07882-7}, url = {https://www.nature.com/articles/s42003-025-07882-7}, author = {Rebecca A. Nelson and Lauren L. Sullivan and Erika I. Hersch-Green and Mahesh Sankaran} } @article {160485, title = {Founders predict trait evolution and population performance after evolutionary rescue in the red flour beetle.}, journal = {Proc Natl Acad Sci U S A}, volume = {122}, year = {2025}, month = {2025 Sep 09}, pages = {e2506244122}, abstract = {

Evolutionary rescue helps populations survive environmental change, but the phenotypic and demographic factors associated with rescue dynamics and its long-term effects remain unclear. We experimentally evolved 10 wild-collected populations of flour beetles from across India in a suboptimal corn resource for 70 generations (\>5 y), collecting \>10,000 population census points book-ended by measurements of fitness-related traits for 30 experimental lines. Despite clear ancestral trait differences, all lines showed highly parallel evolutionary rescue within 20 generations. Long-term average population size varied across source populations and was positively correlated with ancestral development rate, which increased convergently across populations and emerged as the single best predictor of population performance during and after evolutionary rescue. Notably, specific demographic events during rescue (such as the rate of population decline and recovery) were uncorrelated both with ancestral trait distributions and post-rescue adaptation. Our results support prior work showing founder traits as key predictors of adaptation, and highlight their role in long-term adaptation and trait evolution following evolutionary rescue.

}, keywords = {Adaptation, Physiological, Animals, Biological Evolution, Coleoptera, India, Phenotype, Population Density, Population Dynamics}, issn = {1091-6490}, doi = {10.1073/pnas.2506244122}, author = {Ravi Kumar, Vrinda and Buddh, Shyamsunder and Singhal, Shivansh and Prakash, Arun and Agashe, Deepa} } @article {150943, title = {Fragmentation in patchy ecosystems: a call for a functional approach.}, journal = {Trends Ecol Evol}, volume = {40}, year = {2025}, month = {2024 Nov 07}, pages = {27-36}, abstract = {

Habitat fragmentation is a major threat to biodiversity, but existing literature largely ignores naturally patchy ecosystems in favor of forests, where deforestation creates spatially distinct fragments. Here, we use savannas to highlight the problems with applying forest fragmentation principles to spatially patchy ecosystems. Identifying fragmentation using landscape functionality, specifically connectivity, enables better understanding of ecosystem dynamics. Tools and concepts from connectivity research are well suited to identifying barriers other than vegetation structure contributing to fragmentation. Opportunities exist to improve fragmentation mapping by combining remote-sensing data with field measurements related to connectivity to empirically test whether landscapes are functionally fragmented. Advancements in deep learning and increasingly accessible data open many possibilities for comprehensive maps of fragmentation.

}, issn = {1872-8383}, doi = {10.1016/j.tree.2024.09.004}, author = {Benitez, Lorena M and Parr, Catherine L and Sankaran, Mahesh and Ryan, Casey M} } @article {161135, title = {Frequency-Chirped Actuation of Chiral Magnetic Microbots for Viscosity Mapping in Heterogenous Media: From Model Fluids to Living Cells.}, journal = {ACS Nano}, volume = {19}, year = {2025}, month = {2025 Oct 8}, type = {Article}, abstract = {

Fast, accurate, and location-specific measurement of mechanical parameters of complex, heterogeneous environments at the microscale can impact multiple scientific domains. This is a nontrivial technological challenge since the measurement scheme needs to be simultaneously sensitive and fast, such as to obtain meaningful measurements with spatial resolution comparable to the probe dimensions. As we show here, a frequency-chirped external drive with chiral magnetic microbots allows micron-scale spatial resolution with sensitivities better than a few cP/ Hz . Through simultaneous observation of two degrees of freedom, one can measure the local viscosity even when the motion of microbot is severely constr ained. We demonstrate this measurement technique to be applicable in model systems and make spatial maps of viscosity in biologically relevant, inherently heterogeneous, and crowded media, like the cell cytoplasm. The techniques demonstrated in this manuscript establish chiral microbots as a next-generation active, mechanical measurement tool, especially suitable for probing crowded and heterogeneous environments that are ubiquitous in the natural world.

}, keywords = {active mechanical probe, chiral magnetic microbot, Chirp technique, cross-correlation technique, live cell viscometry, local viscosity mapping, microporous media, microrheology, noise floor reduction, ultrafast viscometry}, doi = { https://doi.org/10.1021/acsnano.5c09448 }, author = {Goswami, S{\textquoteright} and Mukherjee, S and Ahmed, N{\textquoteright} and Sreepadmanabh, M{\textquoteright} and Bhattacharjee, T{\textquoteright} and Bhat, R{\textquoteright} and Saini, D{\textquoteright} and Ghosh, A{\textquoteright}} } @article {154352, title = {From low to high elevations, flowers adapt traits and phenology to climate, but phenology-trait relationships weak}, journal = {Functional Ecology}, year = {2025}, month = {26 January 2025}, pages = {1-14}, abstract = {
  1. Flowering phenology is central to plant reproductive success and can relate to morphological traits such as size and quality of flowers, but phenology{\textendash}trait associations of flowers remain unclear. Phenology{\textendash}trait associations can vary within and among species, especially across climate gradients, due to allocational trade-offs in response to selective pressures from abiotic stress and/or biotic factors such as pollinator availability. It is unknown whether floral morphology and phenology experience coordinated selection across climate gradients or vary independently.
  2. Understanding the drivers of trait variation and its implications for floral phenology may be especially relevant in mountains where climate and abiotic gradients change sharply with elevation. At higher elevations, increasing cold and aridity may favour higher quality, stress-tolerant flowers that withstand harsher conditions better than cheaper flowers, but trade-off with size and showiness to pollinators. Relatively benign conditions at lower elevations may permit more flexible phenotypes and weaker association between trait and phenology by allowing species more leeway for flowering times compared with the short growing season at higher elevations.
  3. We examined trait{\textendash}phenology associations within and among 250 herbaceous species in the Western Himalayas, spanning 2000{\textendash}4500 m AMSL. Intraspecific variation in traits and phenology decreased from low to high elevation at the community scale, but species showed idiosyncratic responses. Trait{\textendash}trait correlations indicated stronger selection and constraints on phenotypes and phenology at higher elevations. However, trait{\textendash}phenology correlations were relatively weak throughout, suggesting independent selection on flower morphology vs. phenology.
  4. Overall, climate imposed strong selection on flower traits and regulated floral phenology, but without any strong or consistent associations between traits and phenology. It is likely that flower morphology responded to multiple abiotic and biotic drivers, within and across elevations, whereas phenology mainly responded to temperature and thaw. Our findings suggest that selection from ongoing warming will operate separately on floral morphology and phenology of alpine plant communities, and mechanisms and consequences should be evaluated using experiments.
}, keywords = {Climate Change, floral traits, flower phenology, herbaceous plants, Himalaya, intraspecific trait variation, phenology{\textendash}trait relationships, trait-coordination}, doi = { https://doi.org/10.1111/1365-2435.14748}, url = {https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/1365-2435.14748}, author = {Mustaqeem Ahmad and Sonia Rathee and Meghna Krishnadas} } @article {153394, title = {Frontiers in integrative structural modeling of macromolecular assemblies}, journal = {QRB Discovery}, volume = {6}, year = {2025}, month = {22 January 2025}, pages = {e3}, type = {Research Paper}, abstract = {

Integrative modeling enables structure determination for large macromolecular assemblies by combining data from multiple experiments with theoretical and computational predictions. Recent advancements in AI-based structure prediction and cryo electron-microscopy have sparked renewed enthusiasm for integrative modeling; structures from AI-based methods can be integrated with\ in situ\ maps to characterize large assemblies. This approach previously allowed us and others to determine the architectures of diverse macromolecular assemblies, such as nuclear pore complexes, chromatin remodelers, and cell{\textendash}cell junctions. Experimental data spanning several scales was used in these studies, ranging from high-resolution data, such as X-ray crystallography and AlphaFold structure, to low-resolution data, such as cryo-electron tomography maps and data from co-immunoprecipitation experiments. Two recurrent modeling challenges emerged across a range of studies. First, these assemblies contained significant fractions of disordered regions, necessitating the development of new methods for modeling disordered regions in the context of ordered regions. Second, methods needed to be developed to utilize the information from cryo-electron tomography, a timely challenge as structural biology is increasingly moving towards\ in situ\ characterization. Here, we recapitulate recent developments in the modeling of disordered proteins and the analysis of cryo-electron tomography data and highlight other opportunities for method development in the context of integrative modeling.

}, keywords = {Conformational ensembles, Electron cryo-tomography, Generative modeling, Integrative modeling, Intrinsically disordered proteins, Macromolecular assemblies, Protein language models}, doi = {https://doi.org/10.1017/qrd.2024.15}, url = {https://www.cambridge.org/core/journals/qrb-discovery/article/frontiers-in-integrative-structural-modeling-of-macromolecular-assemblies/BCBF1930939C6E8114D5DC718197C6D2}, author = {Kartik Majila and Shreyas Arvindekar and Muskaan Jindal and Shruthi Viswanath} } @article {161139, title = {Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.}, journal = {Nature Communications}, year = {2025}, type = {Journal}, doi = {https://doi.org/10.1038/s41467-025-64404-z}, author = {Sahu, S{\textquoteright} and Baid, N{\textquoteright} and Aggarwal, D{\textquoteright} and Sharma, A{\textquoteright} and Gun, M{\textquoteright} and Molla, S{\textquoteright} and Sinha, A{\textquoteright} and Dwivedi, A.P{\textquoteright} and Tuli, A{\textquoteright} and Sharma, M{\textquoteright} and Khosla, S{\textquoteright} and Sundaramurthy, Varadharajan and Kumar, A{\textquoteright}} } @article {154339, title = {Future Directions of the Prokaryotic Chromosome Field.}, journal = {Mol Microbiol}, volume = {123}, year = {2025}, month = {2025 Feb}, pages = {89-100}, abstract = {

In September 2023, the Biology and Physics of Prokaryotic Chromosomes meeting ran at the Lorentz Center in Leiden, The Netherlands. As part of the workshop, those in attendance developed a series of discussion points centered around current challenges for the field, how these might be addressed, and how the field is likely to develop over the next 10 years. The Lorentz Center staff facilitated these discussions via tools aimed at optimizing productive interactions. This Perspective article is a summary of these discussions and reflects the state-of-the-art of the field. It is expected to be of help to colleagues in advancing their own research related to prokaryotic chromosomes and inspiring novel interdisciplinary collaborations. This forward-looking perspective highlights the open questions driving current research and builds on the impressive recent progress in these areas as represented by the accompanying reviews, perspectives, and research articles in this issue. These articles underline the multi-disciplinary nature of the field, the multiple length scales at which chromatin is studied in\ vitro and in and highlight the differences and similarities of bacterial and archaeal chromatin and chromatin-associated processes.

}, keywords = {archaeal chromatin; archaeal chromosome; bacterial chromatin; bacterial chromosome; nucleoid.}, issn = {1365-2958}, doi = {10.1111/mmi.15347}, url = {https://pubmed.ncbi.nlm.nih.gov/39977301/}, author = {Abbondanzieri, E A and Badrinarayanan, A B and Barill{\`a}, D and Bell, S D and Blombach, F and Bouet, J Y and Bulgheresi, S and Cao, Q A D and Dame, R T and Dekker, C and Demuysere, M and Esp{\'e}li, O and Fogg, P C M and Freddolino, P L and Ganji, M and Gerson, T M and Grainger, D C and Hamoen, L W and Harju, J and Hocher, A and Hustmyer, C M and Kaljevic, J K and Karney, M K and Kleckner, N and Laloux, G and Landick, R and Lioy, V S and Liu, W L and Liu, C L and M{\"a}kel{\"a}, J and Meyer, A S and Noy, A and Pineau, M P and Premrajka, K and Racki, L R and Rashid, F-Z M and Schnetz, K and Schwab, S and Ti{\v s}ma, M and van der Sijs, A I and van Heesch, T and van Raaphorst, R and Vreede, J and Walker, A W and Walter, J-C and Weber, S C and Wiggins, P A and Wing, H J and Xiao, J and Zhang, Z} } @article {157482, title = {GenDiS3 database: census on the prevalence of protein domain superfamilies of known structure in the entire sequence database.}, journal = {Database (Oxford)}, volume = {2025}, year = {2025}, month = {2025 May 09}, abstract = {

Despite the vast amount of sequence data available, a significant disparity exists between the number of protein sequences identified and the relatively few structures that have been resolved. This disparity highlights the challenge in structural biology to bridge the gap between sequence information and 3D structural data, and the necessity for robust databases capable of linking distant homologs to known structures. Studies have indicated that there are a limited number of structural folds, despite the vast diversity of proteins. Hence, computational tools can enhance our ability to classify protein sequences, much before their structures are determined or their functions are characterized, thereby bridging the gap between sequence and structural data. GenDiS (Genomic Distribution of Superfamilies) is a repository with information on the genomic distribution of protein domain superfamilies, involving a one-time computational exercise to search for trusted homologs of protein domains of known structures against the vast sequence database. We have updated this database employing advanced bioinformatics tools, including DELTA-BLAST (domain enhanced lookup time accelerated BLAST) for initial detection of hits and HMMSCAN for validation, significantly improving the accuracy of domain identification. Using these tools, over 151 million sequence homologs for 2060 superfamilies [SCOPe (Structural Classification of Proteins extended)] were identified and 116 million out of them were validated as true positives. Through a case study on glycolysis-related enzymes, variations in domain architectures of these enzymes are explored, revealing evolutionary changes and functional diversity among these essential proteins. We present another case, LOG gene, where one can tune in and find significant mutations across the evolutionary lineage. The GenDiS database, GenDiS3, and the associated tools made available at https://caps.ncbs.res.in/gendis3/ offer a powerful resource for researchers in functional annotation and evolutionary studies. Database URL: https://caps.ncbs.res.in/gendis3/.

}, keywords = {Computational Biology, Databases, Protein, Protein Domains, Proteins}, issn = {1758-0463}, doi = {10.1093/database/baaf035}, url = {https://academic.oup.com/database/article/doi/10.1093/database/baaf035/8127847?login=true}, author = {Joshi, Sarthak and Mohapatra, Shailendu and Kumar, Dhwani and Joshi, Adwait and Iyer, Meenakshi and Sowdhamini, Ramanathan} } @article {160479, title = {Global selection on insect antipredator coloration.}, journal = {Science}, volume = {389}, year = {2025}, month = {2025 Sep 25}, pages = {1336-1341}, abstract = {

Natural selection has repeatedly led to the evolution of two alternative antipredator color strategies-camouflage to avoid detection and aposematism to advertise unprofitability-but we lack understanding of how ecological context favors one strategy over the other. We conducted a globally replicated predation experiment at 21 sites on six continents to test how predator community, prey community, and visual environment influenced the predation risk of 15,018 artificial paper "moth" prey with cryptic or warning coloration. Results indicated that aposematic strategies fare better in environments with low predation intensity, whereas camouflage strategies are advantaged when other camouflaged prey species are rare and when light levels are low. This study demonstrates how multiple mechanisms shape antipredator strategies, helping to explain the evolution and global distribution of camouflaged and aposematic animals.

}, keywords = {Animals, Biological Evolution, Biological Mimicry, Color, Ecosystem, Insecta, Pigmentation, Predatory Behavior, Selection, Genetic}, issn = {1095-9203}, doi = {10.1126/science.adr7368}, author = {Medina, Iliana and Exnerov{\'a}, Alice and Da{\v n}kov{\'a}, Kl{\'a}ra and Penacchio, Olivier and Sherratt, Tom N and Albrecht, Tom{\'a}{\v s} and Baidya, Sarika and Bosque, Renan Janke and Brown, H{\'e}lo{\"\i}se and Burdfield-Steel, Emily and Cain, Kristal E and Cez{\'a}rio, Rodrigo Roucourt and Chiari, Ylenia and Esquivel, Carolina and Ferreira, Rhainer Guillermo and Franklin, Amanda M and Garvey, Aloise and Guchu, Samuel and Hastings, Brandon T and Hotov{\'a}-Sv{\'a}dov{\'a}, Kate{\v r}ina and Hwang, Yerin and Kang, Changku and Kasaya, John and Kelley, Jennifer and Kim, Yongsu and Kunte, Krushnamegh and Daetto-Liberato, Felipe and Loeffler-Henry, Karl and Lopez, Vinicius Marques and MacKay-Dietrich, Claire and Mappes, Johanna and De M{\'a}rsico, Mar{\'\i}a Cecilia and Nawge, Viraj and Njoroge, Peter and Nokelainen, Ossi and Pal, Arka and Paul, Archan and Posont, Robert and Ra{\v s}ka, Jan and Reboreda, Juan Carlos and Rojas Ripari, Juan Manuel and Rowland, Hannah M and Sabio, Maria de Las Nieves and Salazar, Camilo and Salgado-Roa, Fabian C and Stephens-C{\'a}rdenas, Steve A and Szab{\'o}, Anita and Mongui Torres, Juan Pablo and Troscianko, Jolyon and Truhl{\'a}{\v r}ov{\'a}, Marie and Umbers, Kate D L and Venton, Molly and Vitasovich, Makenzie and Wang, Lu-Yi and Weil, Sarah-Sophie and Allen, William L} } @article {154353, title = {Growth factor-triggered de-sialylation controls glycolipid-lectin-driven endocytosis.}, journal = {Nat Cell Biol}, year = {2025}, month = {2025 Feb 21}, abstract = {

Glycolipid-lectin-driven endocytosis controls the formation of clathrin-independent carriers and the internalization of various cargos such as β1 integrin. Whether this process is regulated in a dynamic manner remained unexplored. Here we demonstrate that, within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell-surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process-mediated by the Na/H antiporter NHE1 as well as the neuraminidases Neu1 and Neu3-requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. De-sialylated glycoproteins are then retrogradely transported to the Golgi apparatus where their glycan make-up is reset to regulate EGF-dependent invasive-cell migration. Further evidence is provided for a role of neuraminidases and galectin-3 in acidification-dependent bone resorption. Glycosylation at the cell surface thereby emerges as a dynamic and reversible regulatory post-translational modification that controls a highly adaptable trafficking pathway.

}, issn = {1476-4679}, doi = {10.1038/s41556-025-01616-x}, url = {https://pubmed.ncbi.nlm.nih.gov/39984654/}, author = {MacDonald, Ewan and Forrester, Alison and Valades-Cruz, Cesar A and Madsen, Thomas D and Hetmanski, Joseph H R and Dransart, Estelle and Ng, Yeap and Godbole, Rashmi and Shp, Ananthan Akhil and Leconte, Ludovic and Chambon, Val{\'e}rie and Ghosh, Debarpan and Pinet, Alexis and Bhatia, Dhiraj and Lombard, B{\'e}rang{\`e}re and Loew, Damarys and Larsen, Martin R and Leffler, Hakon and Lefeber, Dirk J and Clausen, Henrik and Blangy, Anne and Caswell, Patrick and Shafaq-Zadah, Massiullah and Mayor, Satyajit and Weigert, Roberto and Wunder, Christian and Johannes, Ludger} } @article {162677, title = {Histone variants: Distinct building blocks of the chromatin acting at the core.}, journal = {Curr Opin Plant Biol}, volume = {89}, year = {2025}, month = {2025 Dec 04}, pages = {102829}, abstract = {

Histone variants alter the core properties of the nucleosomes they decorate and hence constitute a significant epigenetic layer to control cellular processes. Historically, histone variants have been studied using classical genetics to implicate the functions associated with them. However, over the last few years, advanced (epi)genomics and structural investigations have revealed the fine molecular steps involved in histone variant-specific genome regulation. This review outlines the key mechanistic findings that uncovered both structural and functional aspects of plant histone variants in unprecedented resolution. We also highlight the key avenues that might hold potential for future studies, including chromatin engineering using histone variants.

}, issn = {1879-0356}, doi = {10.1016/j.pbi.2025.102829}, author = {Hari-Sundar Gandhivel, Vivek and Shivaprasad, P V} } @article {156894, title = {Host-Pathogen-Vector Continuum in a Changing Landscape: Potential Transmission Pathways for in a Small Mammal Community.}, journal = {Ecol Evol}, volume = {15}, year = {2025}, month = {2025 Apr}, pages = {e71085}, abstract = {

Bacterial infections account for a large proportion of zoonoses. Our current understanding of zoonotic spillover, however, is largely based on studies from viral systems. Small mammals such as rodents and their ectoparasites present a unique system for studying several bacterial pathogens and mapping their spillover pathways. Using spp. (a Gram-negative bacteria) as a model system within a rainforest human-use landscape, we investigated (1) ecological correlates of prevalence in small mammal hosts and (2) evolutionary relationships between spp. and various hosts and ectoparasites to gain insight into pathogen movement pathways within ecological communities. We detected in five out of eight small mammal species and in 86 (40.56\%) out of 212 individuals, but prevalence varied widely among species (0\%-75.8\%). Seven of the ten ectoparasite species found on these small mammals were positive for . Interestingly, while genotypes (15) in small mammals were host-specific, ectoparasites had nonspecific associations, suggesting the possibility for vector-mediated cross-species transmission. We also found that prevalence in hosts was positively correlated with their aggregated ectoparasite loads, further emphasizing the crucial role that ectoparasites may play in these transmission pathways. Our cophylogenetic analysis and ancestral trait (host) reconstruction revealed incongruence between small mammal and phylogenies, indicating historic host shifts and validating the potential for contemporary spillover events. We found that small mammal hosts in this fragmented landscape often move across habitat boundaries, creating a transmission pathway (via shared ectoparasites) to novel hosts, which may include synanthropic species like . Our results highlight the necessity to disentangle the complex relationship among hosts, ectoparasites, and bacterial pathogens to understand the implications of undetected spillover events.

}, keywords = {bacterial zoonosis; coevolution; ectoparasites; host shifts; vector-borne pathogens.}, issn = {2045-7758}, doi = {10.1002/ece3.71085}, url = {https://pubmed.ncbi.nlm.nih.gov/40177689/}, author = {Ansil, B R and Viswanathan, Ashwin and Ramachandran, Vivek and Yeshwanth, H M and Sanyal, Avirup and Ramakrishnan, Uma} } @article {157491, title = {Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection.}, journal = {PLoS Pathog}, volume = {21}, year = {2025}, month = {2025 May 19}, pages = {e1013164}, abstract = {

Viruses modulate various aspects of host physiology, including carbon metabolism, redox balance, and mitochondrial bioenergetics to acquire the building blocks for replication and regulation of the immune response. Understanding how SARS-CoV-2 alters the host metabolism may lead to treatments for COVID-19. We report that a ubiquitous gaseous molecule, hydrogen sulfide (H2S), regulates redox, metabolism, and mitochondrial bioenergetics to control SARS-CoV-2. Virus replication is associated with down-regulation of the H2S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase (3-MST) in multiple cell lines and nasopharyngeal swabs of symptomatic COVID-19 patients. Consequently, SARS-CoV-2-infected cells showed diminished endogenous H2S levels and a protein modification (S-sulfhydration) caused by H2S. Genetic silencing or chemical inhibition of CTH resulted in SARS-CoV-2 proliferation. Chemical supplementation of H2S using a slow-releasing H2S donor, GYY4137, diminished virus replication. Using a redox biosensor, metabolomics, transcriptomics, and XF-flux analyzer, we showed that GYY4137 blocked SARS-CoV-2 replication by inducing the Nrf2/Keap1 pathway, restoring redox balance and carbon metabolites and potentiating mitochondrial oxidative phosphorylation. Treatment of SARS-CoV-2-infected mice or hamsters with GYY4137 suppressed viral replication and ameliorated lung pathology. GYY4137 treatment reduced the expression of inflammatory cytokines and re-established the expression of Nrf2-dependent antioxidant genes in the lungs of SARS-CoV-2-infected mice. Notably, non-invasive measurement of respiratory functions using unrestrained whole-body plethysmography (uWBP) of SARS-CoV-2-infected mice showed improved pulmonary function variables, including pulmonary obstruction (Penh), end-expiratory pause (EEP), and relaxation time (RT) upon GYY4137 treatment. Together, our findings significantly extend our understanding of H2S-mediated regulation of viral infections and open new avenues for investigating the pathogenic mechanisms and therapeutic opportunities for coronavirus-associated disorders.

}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1013164}, url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013164}, author = {Agrawal, Ragini and Pal, Virender Kumar and K S, Suhas and Menon, Gopika Jayan and Singh, Inder Raj and Malhotra, Nitish and C S, Naren and Ganesh, Kailash and Rajmani, Raju S and Narain Seshasayee, Aswin Sai and Chandra, Nagasuma and Joshi, Manjunath B and Singh, Amit} } @article {154146, title = {Hypoxia-induced CTCF mediates alternative splicing via coupling chromatin looping and RNA Pol II pause to promote EMT in breast cancer.}, journal = {Cell Rep}, volume = {44}, year = {2025}, month = {2025 Feb 04}, pages = {115267}, abstract = {

Hypoxia influences the epithelial-mesenchymal transition (EMT) through the remodeling of the chromatin structure, epigenetics, and alternative splicing. Hypoxia drives CCCTC-binding factor (CTCF) induction through hypoxia-inducible factor 1-alpha (HIF1α), which promotes EMT, although the underlying mechanisms remain unclear. We find that hypoxia significantly increases CTCF occupancy at various EMT-related genes. We present a CTCF-mediated intricate mechanism promoting EMT wherein CTCF binding at the collagen type V alpha 1 chain (COL5A1) promoter is crucial for COL5A1 upregulation under hypoxia. Additionally, hypoxia drives exon64A inclusion in a mutually exclusive alternative splicing event of COL5A1exon64 (exon64A/64B). Notably, CTCF mediates COL5A1 promoter-alternatively spliced exon upstream looping that regulates DNA demethylation at distal exon64A. This further regulates the CTCF-mediated RNA polymerase II pause at COL5A1exon64A, leading to its inclusion in promoting the EMT under hypoxia. Genome-wide study indicates the association of gained CTCF occupancy with the alternative splicing of many cancer-related genes, similar to the proposed model. Specifically, disrupting the HIF1α-CTCF-COL5A1exon64A axis through the dCas9-DNMT3A system alleviates the EMT in hypoxic cancer cells and may represent a novel therapeutic target in breast cancer.

}, keywords = {COL5A1; CP: Cancer; CP: Molecular biology; CRISPR-dCas9-mediated editing; CTCF; EMT; alternative splicing; breast cancer; epigenetics; hypoxia; promoter-exon upstream looping.}, issn = {2211-1247}, doi = {10.1016/j.celrep.2025.115267}, url = {https://pubmed.ncbi.nlm.nih.gov/39913285/}, author = {Kakani, Parik and Dhamdhere, Shruti Ganesh and Pant, Deepak and Joshi, Rushikesh and Mishra, Sachin and Pandey, Anchala and Notani, Dimple and Shukla, Sanjeev} } @article {154152, title = {Identification of Distinct Rodent-Associated Adenovirus Lineages from Mixed-Use Landscape.}, journal = {Ecohealth}, year = {2025}, month = {2025 Feb 04}, abstract = {

Land-use change and increased human-livestock-wildlife interactions have generated numerous possibilities for viral spillover, demanding enhanced surveillance in biodiverse regions. We investigated adenovirus diversity in small mammals, an understudied host taxon, from a forest-plantation mosaic in the Western Ghats biodiversity hotspot. We observed high prevalence (up to 39.39\%) and identified five lineages of adenoviruses with unique mutations in the dominant small mammal species,\ Rattus satarae. These lineages significantly differed from other known murine adenoviruses (p-distance \> 25\%), indicating the likelihood of novel adenoviruses in this endemic small mammal and suggesting potential for unexplored DNA virus diversity in the region.

}, keywords = {DNA viruses; India; small mammals; surveillance.}, issn = {1612-9210}, doi = {10.1007/s10393-025-01700-6}, url = {https://pubmed.ncbi.nlm.nih.gov/39903359/}, author = {Ansil, B R and Sanyal, Avirup and Sreenivas, Darshan and Garg, Kritika M and Ramakrishnan, Uma and Chattopadhyay, Balaji} } @article {158509, title = {Identifying bellwether sewershed sites for sustainable disease surveillance in Bengaluru, India: a longitudinal study}, year = {2025}, abstract = {

Background

Throughout the COVID-19 pandemic, wastewater surveillance emerged as an important tool by providing data that are more representative of the population than case reporting, which is often biased towards individuals with health-seeking behaviour or access to healthcare. With changing phases of the pandemic, decreased testing, and varying viral shedding rates, it is crucial to have a robust, sustainable, and flexible wastewater surveillance system that can serve as an independent signal of disease outbreaks. We aimed to identify {\textquoteleft}bellwether{\textquoteright} sewershed sites for sustainable disease surveillance in Bengaluru, India.

Methods

We conducted this longitudinal study from December 2021 to January 2024 at 26 centralised sewershed sites in Bengaluru city (\~{}11 million inhabitants). We quantified weekly SARS-CoV-2 RNA concentrations to track infection dynamics and identify {\textquoteleft}bellwether{\textquoteright} sewershed sites. This was achieved by integrating established metrics for wastewater analysis, calculating sample-to-sample percentage rate of change, and applying algorithms to differentiate signal from noise, thereby validating factors contributing to the precision and reliability of outbreak predictions.

Findings

Using 2873 wastewater samples, we applied a modified algorithm (COVID-SURGE algorithm) to identify {\textquoteleft}bellwether{\textquoteright} sewershed sites using longitudinal wastewater data on SARS-CoV-2 from 26 sewershed sites in Bengaluru. We utilised an Excel-based calculator (COVID-SURGE calculator) for user-entered wastewater data that differentiates signal from noise (underlying variability) based on the algorithm, with adjustments made to the input format of viral data and a specified limit of detection (LOD) value from the reverse transcriptase-quantitative PCR kit. We identified 11 {\textquoteleft}bellwether{\textquoteright} sites: four with large catchment sizes (KC Valley 1, KC Valley 2, Rajacanal, Doddabelee); four with medium sizes (Agaram, Nagasandra, KR Puram, Yelahanka); and three with small sizes (Chikkabegur, Chikkabanavara, Lalbagh). These were the best performers and can serve as a useful subset of sewage treatment plants for an early warning system at the city level.

Interpretation

Using wastewater metrics helps in selecting permanent sewershed sites and identifying sub-sites that can be scaled up during peak outbreak periods to detect disease hotspots, or scaled down during lean periods, especially when clinical data are unavailable. In a post-pandemic world, particularly in low-resource settings, focusing on the best-performing sewershed sites will ensure high-quality data that captures valid signals amid the noise from wastewater, conserves resources, and optimises public health actions beyond SARS-CoV-2.

Funding

This work has been supported by funding from the Rockefeller Foundation (grant 2021 HTH018) to National Centre for Biological Sciences (TIFR) and the Indian Council of Medical Research grant to (FI) Tata Institute for Genetics and Society and Tata Trusts.
}, keywords = {Wastewater surveillance SARS-CoV-2 COVID-SURGE India Bengaluru COVID-19 Variants Pandemic COVID-19 pandemic Low-resource settings}, doi = {10.1016/j.lansea.2025.100619 External Link}, url = {https://www.thelancet.com/journals/lansea/article/PIIS2772-3682(25)00090-3/fulltext}, author = {Rebecca Fern Daniel and Subash K. Kannan and Namrta Daroch and Sutharsan Ganesan and Farhina Mozaffer and Vishwanath Srikantaiah and Lingadahalli Subrahmanya Shashidhara and Rakesh Mishra and Farah Ishtiaq} } @article {162693, title = {IHMValidation: Assessment of Integrative Structure Models Deposited to the Protein Data Bank.}, journal = {J Mol Biol}, year = {2025}, month = {2025 Dec 18}, pages = {169598}, abstract = {

PDB-IHM is a branch of the Protein Data Bank (PDB), a Worldwide Protein Data Bank (wwPDB) Core Archive, that expands its scope by allowing for additional biomolecular structure representations and types of experimental information (i.e., integrative/hybrid structure models). As of October 2025, PDB-IHM contained 374 entries, benefitting from multi-scale and multi-state representations and 17 types of experimental data. These structure models are assigned PDB accession codes and are archived alongside other experimental structures in the PDB. Rigorous interpretation of a structure model requires assessment of underlying data quality, consistency with the input data, and estimates of positional uncertainty of its components. Herein, we present the IHMValidation pipeline (https://validate.pdb-ihm.org; https://github.com/salilab/IHMValidation) based on recommendations from the wwPDB Integrative Methods Task Force plus the small-angle scattering (SAS), chemical crosslinking mass spectrometry (crosslinking-MS), and cryo-electron microscopy and tomography (3DEM) communities. The IHMValidation report (available in both PDF and HTML formats) comprises six sections: (i) overview; (ii) model details; (iii) data quality assessments; (iv) local geometry assessments (i.e., model quality); (v) fit of the model to the data used to generate it; and (vi) fit of the model to the data used for validation. Future expansions of the IHMValidation pipeline will: (i) reflect recommendations coming from additional experimental communities, including F{\"o}rster resonance energy transfer (FRET) and hydrogen/deuterium exchange MS (HDX-MS); (ii) include other validation criteria, such as Bayesian likelihoods for the data; and (iii) represent estimates of structure model uncertainty based on the variation among alternative models satisfying input data.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2025.169598}, author = {Zalevsky, Arthur O and Vallat, Brinda and Webb, Benjamin M and Tangmunarunkit, Hongsuda and Sekharan, Monica R and Shafaeibejestan, Aref and Ganesan, Sai and Sagendorf, Jared and Jeffries, Cy M and Trewhella, Jill and Graziadei, Andrea and Vizca{\'\i}no, Juan Antonio and Leitner, Alexander and Rappsilber, Juri and Peisach, Ezra and Flatt, Justin W and Young, Jasmine Y and Majila, Kartik and Viswanath, Shruthi and Kesselman, Carl and Hoch, Jeffrey C and Kurisu, Genji and Morris, Kyle L and Velankar, Sameer and Berman, Helen M and Burley, Stephen K and Sali, Andrej} } @article {160489, title = {Inheritable cell-states shape drug-persister correlations and population dynamics in cancer cells.}, journal = {PLoS Comput Biol}, volume = {21}, year = {2025}, month = {2025 Sep}, pages = {e1013446}, abstract = {

Drug tolerant persisters (DTPs) drive cancer therapy resistance by temporarily evading drug action, allowing multiple routes to eventual permanent resistance. Despite clear evidence for DTPs, the timing of their emergence, proliferative nature, and how their population dynamics arise from measured single-cell kinetics remain poorly understood. Here we use time-lapse microscopy data from two cancer cell lines, integrating single-cell and population measurements, to develop a quantitative description of drug persistence. Contrary to the expectation that increasing levels of genotoxic stress should lead to slower times to division and faster times to death, we observe minor changes in the single-cell intermitotic and death time distributions upon increasing cisplatin concentration. Yet, population decay rates increase 3-fold, suggesting a surprising independence of the overall dynamics from the measured birth and death rates. To explain this phenomenon, we argue that the observed lineage correlations and concentration-dependent decay rates imply cell-state dependent fate choices made both pre and post-cisplatin as opposed to just post-drug birth/death rate-based competitive fate choices. We demonstrate that these cell-states, present in the pre-drug ancestors of DTP and sensitive cells, exhibit no difference in cycling speed and are inherited across at least 2-3 cellular generations. Post-drug survival versus death fates are decided with high probability by these pre-existing cell-states, but get modulated to some extent by the drug, leading to a drug concentration dependent state-fate map. A stochastic model implementing these rules simultaneously recapitulates the observed decay rates and cell-fate lineage correlations. The model also demonstrates how the use of barcode diversity change before and after drug might lead to misleading interpretations of the timing of persister fate decisions. Our results provide a conceptual framework for quantifying pre versus post-drug contributions to cell fate, without requiring knowledge of the underlying molecular architecture of the heterogeneous cell states.

}, keywords = {Antineoplastic Agents, Cell Line, Tumor, Cisplatin, Computational Biology, Drug Resistance, Neoplasm, Humans, Models, Biological, Neoplasms, Single-Cell Analysis, Time-Lapse Imaging}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1013446}, author = {Iyer, Anton and Alva, Adrian and Granada, Adri{\'a}n E and Chakrabarti, Shaon} } @article {161136, title = {Ionic conductances driving tonic firing in Purkinje neurons of larval zebrafish.}, journal = { Journal of Physiology}, year = {2025}, month = {11 Sep 2025}, abstract = {

Purkinje neurons are critical for the functioning of the cerebellum, which is among the oldest and most conserved regions of the vertebrate brain. In mammals and in larval zebrafish, Purkinje neurons can generate tonic firing even when isolated from the network. Here we investigated the ionic basis of tonic firing in Purkinje neurons of larval zebrafish using voltage clamp for isolation of membrane currents along with pharmacology. We discovered that these neurons express L-type and P/Q-type high voltage-gated calcium currents, T-type low voltage-gated calcium currents and SK and BK-type calcium-dependent potassium currents. Among these, L-type calcium currents and SK-type calcium-dependent potassium currents were indispensable for tonic firing, while blocking T-type, P/Q-type and BK currents had little effect in comparison. We observed that action potentials were broadened when either L-type or SK channels were blocked. Based on these results, we propose that calcium entry via L-type calcium channels activates SK potassium channels leading to faster action potential repolarization, in turn aiding the removal of inactivation of sodium channels. This allows larval zebrafish Purkinje neurons to continue to fire tonically for sustained periods. In mammals also, tonic firing in Purkinje neurons is driven by calcium channels coupling to calcium-dependent potassium channels, yet the specific types of channels involved are different. We therefore suggest that coupling of calcium channels and calcium-dependent potassium channels could be a conserved mechanism for sustaining long bouts of high frequency firing.

}, issn = {0022-3751}, doi = {https://doi.org/10.1113/JP286063}, author = {Jadhav, M.P{\textquoteright} and Verma,S{\textquoteright} and Thirumalai, V{\textquoteright}} } @article {155540, title = {Ionic Liquid-Induced Modulation of Ubiquitin Stability: The Dominant Role of Hydrophobic Interactions.}, journal = {Langmuir}, volume = {41}, year = {2025}, month = {2025 Mar 11}, pages = {5823-5837}, abstract = {

Despite the widespread use of imidazolium-based ionic liquids (ILs) in biotechnology, pharmaceuticals, and green chemistry, their detailed interactions with proteins, particularly affecting structural stability, remain poorly understood. This study examines the effects of ILs on ubiquitin, a thermodynamically robust protein with a β-grasp structure. We found that IL-induced destabilization follows a consistent order with previous findings: [BMIM] \> [BMPyr] \> [EMIM] for cations and [BF] \> [MeSO] \> [Cl] for anions. Through pH and ionic strength-dependent studies, we observed that hydrophobic interactions predominantly influence the stability of positively charged ubiquitin, with electrostatic interactions playing a secondary role. NMR studies identified residues impacted by [BMIM][BF]; however, site-directed mutagenesis of these residues showed minimal changes in destabilization, suggesting a global effect. This led us to conduct a broader empirical analysis, incorporating solvent-accessible surface area evaluations, which confirmed that hydrophobic residues are the primary drivers of stability alterations in ubiquitin, with charged residues playing a minimal role. Additionally, single-molecule force spectroscopy results indicate that imidazolium ILs lower the unfolding barrier without altering the transition state structure, offering insights into protein folding dynamics. ILs appear to modulate the stability landscape of proteins by energetically and kinetically favoring the unfolded state over the folded state. These insights offer potential strategies for the selective tuning of protein stability, which could be exploited to modulate protein-protein or protein-substrate interactions in various applications of ILs.

}, keywords = {Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Imidazoles, Ionic Liquids, Protein Stability, Thermodynamics, Ubiquitin}, issn = {1520-5827}, doi = {10.1021/acs.langmuir.4c03886}, url = {https://pubmed.ncbi.nlm.nih.gov/40065704/}, author = {Shrivastava, Aditya and Kamma, Harika and Das, Ranabir and Ainavarapu, Sri Rama Koti} } @article {156898, title = {Junctional force patterning drives both positional order and planar polarity in the auditory epithelia.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Apr 26}, pages = {3927}, abstract = {

Tissue function depends on the precise organisation of the constituent cells. In the cochlea, the fidelity of hearing depends on mechanosensory hair cells being consistently surrounded by supporting cells. In addition to this positional order, auditory sensitivity depends crucially on planar cell polarity. This is characterised by the alignment of the orientation of eccentrically placed hair bundles on each hair cell. These two levels of order emerge simultaneously despite the cellular fluxes that occur during cochlear development. However, the link between tissue-scale cellular rearrangements and intrinsic cellular mechanisms remains unknown. By combining experimental and theoretical approaches, we find a precise force patterning underpinning positional order and planar cell polarity. This occurs through the modulation of the levels and phospho-type of the regulatory light chain of non-muscle myosin II at specific cell-cell junctions of the auditory epithelium. We propose that the control of junctional mechanics is vital for the organisation of multi-cell-type epithelia.

}, keywords = {Animals, Cell Polarity, Cochlea, Epithelium, Hair Cells, Auditory, Intercellular Junctions, Mice, Myosin Light Chains, Myosin Type II}, issn = {2041-1723}, doi = {10.1038/s41467-025-58557-0}, url = {https://www.nature.com/articles/s41467-025-58557-0}, author = {Prakash, Anubhav and Weninger, Julian and Singh, Nishant and Raman, Sukanya and Rao, Madan and Kruse, Karsten and Ladher, Raj K} } @article {159719, title = {K. VijayRaghavan.}, journal = {Curr Biol}, volume = {35}, year = {2025}, month = {2025 Jul 21}, pages = {R695-R697}, abstract = {

Interview with K. VijayRaghavan, who studies the development of muscles and the nervous system at the Tata Institute of Fundamental Research.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2025.06.026}, author = {VijayRaghavan, K} } @article {161985, title = {Linking eras and data: natural history collections as the foundation of India{\textquoteright}s biodiversity science.}, year = {2025}, abstract = {

India, one of the world{\textquoteright}s most biodiverse countries and now the most populous, stands at a critical intersection of ecological wealth and intense anthropogenic pressure. Its unique geological history, once part of Gondwana and later colliding with Asia, has profoundly shaped its biota, resulting in high levels of endemism and evolutionary distinctiveness. Despite a deep cultural reverence for nature, much of India{\textquoteright}s biodiversity, its distribution, evolutionary origins, and future trajectory remain poorly understood. At the heart of shaping a resilient future for biodiversity science in India lies the urgent need for a modern, accessible, and integrated biodiversity research. Here, we assess the current state of biodiversity science in India, drawing from taxonomic and biogeographical studies that rely heavily on natural history collections. For many taxa and ecosystems, data remain scarce or outdated, often based on collections from the 19th and 20th centuries, with critical gaps in molecular, distributional, and phenotypic trait information. Existing data are frequently fragmented, inaccessible, or poorly integrated. These limitations hinder the ability to understand biogeographical patterns or monitor biodiversity change during the Anthropocene. We argue that a national institution dedicated to biodiversity research is urgently needed to coordinate the documentation, analysis, and conservation of India{\textquoteright}s natural heritage for future generations.

}, keywords = {Biodiversity Science, Fossils and living species, India, Natural History Collections}, doi = {https://doi.org/10.1093/biolinnean/blaf100}, author = {Jahnavi, Joshi and Pritha, Dey and Ashwini V, Mohan and Vijay, Barve and Guntupalli V R, Prasad and Anjali, Goswami and Sandeep, Pulla and Navendu, Page and Ishan, Agarwal and Kartik, Shanker and K Praveen, Karanth and Uma, Ramakrishnan and Devapriya, Chattopadhyay} } @article {156900, title = {Live tracking of replisomes reveals nutrient-dependent regulation of replication elongation rates in Caulobacter crescentus.}, journal = {Curr Biol}, volume = {35}, year = {2025}, month = {2025 Apr 21}, pages = {1816-1827.e3}, abstract = {

In bacteria, commitment to genome replication (initiation) is intricately linked to nutrient availability. Whether growth conditions affect other stages of replication beyond initiation remains to be systematically studied. To address this, we assess the replication dynamics of Caulobacter crescentus, a bacterium that undergoes only a single round of replication per cell cycle, by tracking the replisome across various growth phases and nutrient conditions. We find that the replication elongation rates slow down as cells transition from exponential (high-nutrient) to stationary (low-nutrient) phase, and this contributes significantly to the overall cell-cycle delay. Although elongation rates are correlated with growth rates, both properties are differentially influenced by nutrient status. This slowdown in replication progression is reversed via supplementation with dNTPs and is not associated with increased mutagenesis or upregulation of the DNA damage responses. We conclude that growth conditions not only dictate the commitment to replication but also the rates of genome duplication. Such regulation appears to be distinct from stress-induced replication slowdown and likely serves as an adaptive mechanism to cope with fluctuations in nutrient availability in the environment.

}, keywords = {Caulobacter crescentus; DNA replication; live-cell imaging; replication regulation; replisome dynamics; stationary phase.}, issn = {1879-0445}, doi = {10.1016/j.cub.2025.03.009}, url = {https://pubmed.ncbi.nlm.nih.gov/40168985/}, author = {Adhikashreni, Inchara S and Joseph, Asha Mary and Phadke, Sneha and Badrinarayanan, Anjana} } @article {158950, title = {Long-term ecological monitoring in India: A synthesis.}, year = {2025}, abstract = {

Long-term ecological monitoring (LTEM) is crucial for understanding ecological processes and responses to environmental change, informing management of natural resources, and biodiversity conservation. Systematic LTEM efforts began in India in the mid-1900s, but there is a lack of comprehensive synthesis of LTEM efforts in the country. Here, we use a wide-ranging questionnaire survey of LTEM efforts coupled with a survey of published literature on LTEM efforts in India to synthesise their thematic and geographical spread, and types of data being collected, and identify key challenges to the establishment and maintenance of LTEM projects in the country. Studies monitor 77 unique subjects across 272 LTEM efforts in India. LTEM efforts are more often located in the Western Ghats and Eastern Himalaya, focused on forest vegetation, and monitoring factors such as abundance, distribution, species richness, and biomass. Regions such as North-Eastern, Eastern, Central, and North-Western India, ecosystems such as grasslands, deserts and wetlands, organisms such as macrofungi, amphibians, and reptiles (other than turtles) are underrepresented. Short turnover times of funding and permits were most frequently reported as hurdles in sustaining LTEM efforts. Data from LTEM efforts have been largely used to produce academic outputs such as journal articles, but have also found use for on-the-ground conservation efforts. Overall, this synthesis can help draw attention to the need for systematic long-term ecological monitoring, help efficient utilisation of existing long-term ecological data, identify regions, species and ecosystem components that are underrepresented in Indian LTEM efforts, foster collaborations, and serve as a starting point to address challenges in sustaining LTEM efforts in India.

}, keywords = {Questionnaire survey; Permanent plots; Biodiversity;Conservation;Research infrastructure; Tropical ecosystems}, doi = {https://doi.org/10.1016/j.biocon.2025.111344 }, author = {"Thiruvaimozhi, Y V and Borah, J and Kala, C P and Kunte, K and Patel, B and Sreejith, K A and Thadani, R and Osuri, A.M and Ghosh-Harihar, M} } @article {158511, title = {Long-Term Genomic Surveillance of SARS-CoV-2 in Campus Wastewater Depicts Lineage Trends and Public Health Implications during and after Omicron Waves}, year = {2025}, abstract = {

SARS-CoV-2 transmission and detection on academic campuses in low- to middle-income countries has not been explored. The present study explored wastewater surveillance of SARS-CoV-2 in a campus setting in Pune, Maharashtra, India, offering insights into variant-specific trends and their correlation with clinical cases over a 2.5 year period from November 2021 to April 2024. We collected 242 wastewater samples from the campus sewershed and processed them to extract RNA and perform RT-qPCR and sequencing, followed by lineage assignment using the LCS tool. Early signals of different SARS-CoV-2 variants, such as BA.2.X, JN.1.X, and KP.2.X, were detected in wastewater prior to its first clinical report in Maharashtra, India. Wastewater viral load strongly correlated with clinical cases during the Omicron phase (ρ = 0.73{\textendash}0.81) compared to the post-Omicron phase (ρ = -0.06 to 0.31). This study also highlights that alerts and warnings issued on the basis of wastewater viral hikes have proven instrumental in preventing outbreaks of SARS-CoV-2 variants on campus. However, downgrading COVID-19 from pandemic status by the WHO resulted in a subsequent decrease in public vigilance, changing the viral dynamic in the last phase of the study. This study showcases the utility of wastewater surveillance in a campus setting as an early warning system and understands the interplay of public health policy effects in viral dynamics within controlled ecosystems, such as campuses or offices.

}, doi = {https://doi.org/10.1021/envhealth.5c00048}, url = {https://pubs.acs.org/doi/full/10.1021/envhealth.5c00048}, author = {Paramanik{\textquoteright}, R{\textquoteright} and Rajput, V{\textquoteright} and Malik, V{\textquoteright} and Nannaware, K{\textquoteright} and Matra, S{\textquoteright} and Joshi, S{\textquoteright} and Kumar, S{\textquoteright} and Samson, R{\textquoteright} and Yadav, RK{\textquoteright} and Shah, P{\textquoteright} and Shashidhara, LS{\textquoteright}} } @article {162685, title = {Loss of function of chromatin remodeler OsCLSY4 leads to RdDM-mediated mis-expression of endosperm-specific genes affecting grain qualities.}, journal = {PLoS Genet}, volume = {21}, year = {2025}, month = {2025 Dec}, pages = {e1011956}, abstract = {

In plants, RNA-directed DNA methylation (RdDM) sequence-specifically targets transposable elements (TEs) and repeats, often in a tissue-specific manner. In triploid endosperm tissue, RdDM also acts as a parental dosage regulator, mediating spatio-temporal expression of genes required for its development. It is unclear how RdDM is initiated and established in endosperm. Rice endosperm-specific imprinted chromatin remodeler OsCLSY3 recruits RNA polymerase IV to specific genomic sites for silencing and optimal gene expression. Here we show that, in addition to OsCLSY3, ubiquitously expressed OsCLSY4 is also crucial for proper reproductive growth and endosperm development. Loss of function of OsCLSY4 led to reproductive and nutrient-filling defects in endosperm. Using genetic and molecular analysis, we show that both OsCLSY3 and OsCLSY4 play overlapping and unique silencing roles in rice endosperm, by targeting specific and shared genomic regions such as TEs, repeats and genic regions. These results indicate the importance of optimal expression of two OsCLSYs in regulating endosperm-specific gene expression, genomic imprinting and suppression of specific TEs. Results presented here provide new insights into the functions of rice CLSYs as upstream RdDM regulators in rice endosperm development, and we propose that functions of their homologs might be conserved across monocots.

}, keywords = {Chromatin Assembly and Disassembly, DNA Methylation, DNA Transposable Elements, Edible Grain, Endosperm, Gene Expression Regulation, Plant, Genomic Imprinting, Oryza, Plant Proteins}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1011956}, author = {Pal, Avik Kumar and Rana, Saumyapriya and Dey, Riju and Shivaprasad, Padubidri V} } @article {156923, title = {Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson{\textquoteright}s disease}, year = {2025}, doi = {10.1083/jcb.202412055}, url = {https://doi.org/10.1083/jcb.202412055}, author = {Martina Gregori and Gustavo J.S. Pereira and Robert Allen and Nicholas West and Kai-Yin Chau and Xinjiang Cai and Matthew P. Bostock and Stephen R. Bolsover and Marco Keller and Chiao-Yin Lee and Si Hang Lei and Kirsten Harvey and Franz Bracher and Christian Grimm and Gaiti Hasan and Matthew E. Gegg and Anthony H.V. and Sean T. Sweeney and Sandip Patel} } @article {157492, title = {M. tuberculosis surface sulfoglycolipid SL-1 activates the mechanosensitive channel TRPV4 to enhance lysosomal biogenesis and exocytosis in macrophages}, journal = {Mol Biol Cell}, volume = {36}, year = {2025}, month = {2025 Jun 01}, pages = {ar76}, abstract = {

Intracellular pathogens manipulate host cellular pathways to ensure their survival. (Mtb) disrupts phagosomal trafficking to prevent fusion with lysosomes. Beyond this localized effect, Mtb globally remodels the host lysosomal system, predominantly through its virulence-associated surface lipid, sulfolipid-1 (SL-1). SL-1 enhances lysosomal biogenesis via the mTORC1-TFEB axis; however, the upstream mediators remain unknown. Here, we show that SL-1 induces calcium influx into macrophages and identify the mechanosensitive calcium channel transient receptor potential vanilloid subtype 4 (TRPV4) as a crucial upstream mediator of SL-1-induced lysosomal remodeling. TRPV4 influences multiple aspects of lysosomal function, including biogenesis, acidification, enzymatic activity, phagosome maturation, and lysosomal exocytosis. These effects are recapitulated during Mtb infection, underscoring the relevance of SL-1- and TRPV4-dependent lysosomal remodeling in an infection context. TRPV4 expression is upregulated during Mtb infection and partially localizes to both lysosomes and the Mtb-containing vacuole. Remarkably, TRPV4 activation, independent of SL-1, is sufficient to enhance lysosomal biogenesis, identifying TRPV4 as a key regulator of lysosomal homeostasis. Together, these findings uncover a novel mechanism of lysosomal remodeling driven by a pathogen lipid virulence factor and reveal a previously unrecognized role for TRPV4 in modulating lysosomal homeostasis in macrophages.

}, keywords = {Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Calcium, Exocytosis, Glycolipids, Humans, Lysosomes, Macrophages, Mice, Mice, Inbred C57BL, Mycobacterium tuberculosis, Phagosomes, TRPV Cation Channels}, issn = {1939-4586}, doi = {10.1091/mbc.E24-12-0560}, url = {https://www.molbiolcell.org/doi/10.1091/mbc.E24-12-0560?url_ver=Z39.88-2003\&rfr_id=ori:rid:crossref.org\&rfr_dat=cr_pub\%20\%200pubmed}, author = {Umar, Ibrahim and Gulzar, Shah-E-Jahan and Sundaramurthy, Varadharajan} } @article {156536, title = {Mapping genetic diversity with the GenomeIndia project.}, journal = {Nat Genet}, volume = {57}, year = {2025}, month = {2025 Apr}, pages = {767-773}, chapter = {767}, abstract = {

The rich ethnolinguistic and sociocultural differences that exist in India offers a unique opportunity to study human diversity. With the whole genomes of 10,000 healthy and unrelated Indians from 83 populations, the GenomeIndia project captures the genetic diversity of one of the highly underrepresented populations in the global genomics landscape.

India, the most populous nation in the world with 1.44 billion people from over 4,600 distinct endogamous groups, represents an invaluable source of ethnolinguistic, sociocultural and genetic diversity. Deciphering the genetic makeup of human populations helps in understanding their ancestry, evolutionary history, admixture patterns, disease susceptibility and drug response. To this end, world over, genomics consortia have been established. Nevertheless, the global genomic landscape is predominantly Euro-centric1; although some projects have documented worldwide genetic diversity by discovering DNA sequence variation in several human populations, for example the 1000 Genomes project2, followed by others across the world, recent inclusions being at biobank scale3,4,5,6,7. Unfortunately, India has been severely underrepresented in these global studies. To address this lacuna, a few studies have been initiated to understand the human genetic diversity of Asia (GenomeAsia)8\ and India (IndiGen and LASI-DAD)9,10.

India experienced several waves of migration11,12\ with evidence of population expansion during the Paleolithic and Neolithic periods. The demographic history of India is also unique, with exposure to different environments and widespread admixture, followed by formation of numerous endogamous groups13. Many of the contemporary Indian populations have originated from a few founding groups and have maintained distinct identities through centuries of endogamy. These endogamous groups13,14, apart from sharing genetic similarities, possess unique variations, including distinct disease-causing mutations with amplified frequencies within specific groups.

}, issn = {1546-1718}, doi = {10.1038/s41588-025-02153-x}, url = {https://www.nature.com/articles/s41588-025-02153-x}, author = {Bhattacharyya, Chandrika and Subramanian, Krithika and Uppili, Bharathram and Biswas, Nidhan K and Ramdas, Shweta and Tallapaka, Karthik Bharadwaj and Arvind, Prathima and Rupanagudi, Khader Valli and Maitra, Arindam and Nagabandi, Tulasi and De, Tiyasha and Singh, Kuldeep and Sharma, Praveen and Sharma, Nanaocha and Raghav, Sunil K and Prasad, Punit and Soniya, E V and Jaleel, Abdul and Nelson Sathi, Shijulal and Joshi, Madhvi and Joshi, Chaitanya and Lahiri, Mayurika and Dixit, Santosh and Shashidhara, L S and Senthil Kumar, Nachimuthu and Lalhruaitluanga, H and Nundanga, Lal and Shivakumar, Venkataram and Venkatasubramanian, Ganesan and Rao, Naren P and Ganie, Mohd Ashraf and Wani, Imtiyaz Ahmad and Jha, Ganganath and Dalal, Ashwin and Bashyam, Murali Dharan and Varadwaj, Pritish Kumar and Bs, Sanjeev and Simmhan, Yogesh and Jain, Chirag and Sundar, Durai and Gupta, Ishaan and Yadav, Pankaj and Sinha, Himanshu and Narayanan, Manikandan and Raman, Karthik and Padinjat, Raghu and Sabarinathan, Radhakrishnan and Narahari, Yadati and Ravindranath, Vijayalakshmi and Kumarasamy, Thangaraj and Sowpati, Divya Tej and Faruq, Mohammed and Basu, Analabha and Kahali, Bratati} } @article {160487, title = {Measurement of Substrate SUMOylation in Real Time by Fluorescence Spectroscopy.}, journal = {Methods Mol Biol}, volume = {2957}, year = {2025}, month = {2025}, pages = {159-168}, abstract = {

Post-translational modifications, such as SUMOylation, play a crucial role in regulating various cellular processes. Traditionally, in vitro SUMOylation assays are carried out using techniques like SDS-PAGE gels and Western blotting, which are often time consuming. These informative methods, which quantitate the increase in substrate{\textquoteright}s molecular weight, can introduce potential errors and thus a need arises for a more efficient and accurate alternative. We propose a real-time detection method for SUMOylation that utilizes a fluorescence-tagged substrate, which has been recently developed by our group (Tripathi and Das, CP Protein Sci 101:e111, 2020). We believe this method has the potential to significantly enhance the efficiency and accuracy of SUMOylation assessment, thereby advancing our understanding of SUMO signaling and its function.

}, keywords = {Humans, Protein Processing, Post-Translational, Small Ubiquitin-Related Modifier Proteins, Spectrometry, Fluorescence, Sumoylation}, issn = {1940-6029}, doi = {10.1007/978-1-0716-4710-3_11}, author = {Puri, Anindita and Tripathi, Vasvi and Das, Ranabir} } @article {157481, title = {Mechanisms and implications of high depolarization baseline offsets in conductance-based neuronal models.}, journal = {J Neurophysiol}, year = {2025}, month = {2025 May 19}, abstract = {

Somatic step-current injection is commonly used to characterize the electrophysiological properties of neurons. Many neuronal types show a large depolarization baseline offset (DBLO), which is defined as the positive difference between the minimum membrane potential during action potential trains and resting. We used stochastic parameter search in experimentally constrained conductance-based models to show that four key factors together account for high DBLO: Liquid Junction Potential correction, high backpropagating passive charges during the repolarization phase of an action potential, fast potassium delayed rectifier kinetics, and appropriate transient sodium current kinetics. Several plausible mechanisms for DBLO, such as Ohmic depolarization due to current input or low-pass filtering by the membrane, fail to explain the effect, and many published conductance-based models do not correctly manifest high DBLO. Finally, physiological levels of DBLO constrain ion channel levels and kinetics, and are linked to cellular processes such as bistable firing, spikelets, and calcium influx.

}, issn = {1522-1598}, doi = {10.1152/jn.00617.2024}, url = {https://journals.physiology.org/doi/abs/10.1152/jn.00617.2024?url_ver=Z39.88-2003\&rfr_id=ori:rid:crossref.org\&rfr_dat=cr_pub\%20\%200pubmed}, author = {Kumar, Anal and Shahul, Anzal K and Bhalla, Upinder Singh} } @article {161984, title = {Mechanosensory cephalic bristles mediate rapid flight initiation in hawkmoths.}, journal = {J Comp Physiol A Neuroethol Sens Neural Behav Physiol}, year = {2025}, month = {2025 Oct 31}, abstract = {

Endothermic insects including bees, butterflies, and moths need to warm up their flight muscles before taking flight. For instance, diurnal butterflies bask in the sun to heat their flight muscles, whereas nocturnal hawkmoths display a pre-flight shivering behavior in which small-amplitude wing movements cause flight muscles to warm up, eventually generating large-amplitude wing motion for flight. The time required for warm-up puts such insects at considerable risk if they need to rapidly escape from predators. Here, we show that upon experiencing a sudden air-puff on the head, hawkmoths with lower thoracic temperatures can rapidly initiate flight without the need for pre-flight shivering. This response is mediated by mechanosensory cephalic bristles that are located beneath the scales on their head. When activated, these bristles trigger a set of flight-related reflexes including antennal positioning, foreleg extension, wing movement, and abdominal flexion. Some of the mechanosensory neurons associated with the cephalic bristles arborize in the subesophageal zone (SEZ) and antennal motor and mechanonsensory centre (AMMC), whereas most arborize in pro-, meso- and meta-thoracic ganglia, which contain the motor circuitry for foreleg motion, flight, and abdominal flexion. Thermal recordings revealed that large-amplitude flapping following cephalic bristle-stimulation occurs at lower thoracic temperatures than required for endogenously-initiated take off. Electromyogram recordings from steering and indirect flight muscles show significant variability in activation latency in response to cephalic bristle stimuli. The range of latency values among different muscles overlaps, suggesting that cephalic bristle stimulation broadly activates indirect flight and steering muscles, thereby generating high-amplitude wing movement at lower thoracic temperatures. Thus, akin to locusts, the cephalic bristle system in hawkmoths rapidly triggers flight upon sensing danger, ensuring swift escape from potential threats.

}, keywords = {Daphnis nerii; Cephalic bristles; Endothermy; Flight reflexes; Hawkmoths; Insect flight; Pre-flight shivering}, issn = {1432-1351}, doi = {10.1007/s00359-025-01762-5}, author = {Manjunath, Maitri and Sane, Sanjay P} } @article {157489, title = {Metabolic Diversity of a Widely Distributed Tropical Freshwater Crab Is Not Underpinned by Genetic Differences}, journal = {Journal of Biogeography}, year = {2025}, month = {26 April 2025}, abstract = {

Aim

The aim of this study was to understand the interplay between local and regional factors as drivers of population physiological diversity in a tropical freshwater crab species.

Location

Western Ghats, south-west India.

Taxon

Barytelphusa cunicularis,\ Brachyura, Crustacea.

Methods

We applied an integrative approach combining population genetics and whole animal physiology, using the tropical freshwater crab\ Barytelphusa cunicularis\ as our model species. We tested for effects of population location (e.g., latitude, altitude), season (as a proxy for rainfall and water temperature) and/or warming on indices of whole animal respiratory physiology (metabolic rate, MO2) and hypoxic performance (Pcrit, i.e., the PO2\ at which routine MO2\ can no longer be sustained) in five widely distributed populations of this species. We also generated population genetic data (mtDNA COI and nDNA histone H3 sequences) to determine the extent of any population genetic structuring and/or cryptic species diversity present to verify that we were investigating a single species.

Results

Despite a high level of genetic structuring between the different populations of\ B. cunicularis\ examined, the genetic distances observed were consistent with intra- and not interspecific differences in freshwater crabs. Populations varied in the diversity of the physiological (MO2) responses observed. There were significant effects of season and population on respiration in response to temperature and Pcrit\ in response to acute hypoxia.

Main Conclusions

We conclude that local environmental factors are important in shaping physiological diversity between populations in tropical freshwater species and systems. This highlights the need to include population-level responses in any projections we make on how biodiversity will respond to ongoing and future environmental changes, including those caused by climate change.

}, doi = {https://doi.org/10.1111/jbi.15147}, url = {https://onlinelibrary.wiley.com/doi/10.1111/jbi.15147}, author = {Lucy M. Turner and Christopher J. Thorpe and Michael Collins and Smrithy Raj and Tripti Shukla and John I. Spicer and Mairi E. Knight and Dheeraj Sharma and Krushnamegh Kunte} } @article {158505, title = {Metabolically driven flows enable exponential growth in macroscopic multicellular yeast}, year = {2025}, abstract = {

The ecological and evolutionary success of multicellular lineages stems substantially from their increased size relative to unicellular ancestors. However, large size poses biophysical challenges, especially regarding nutrient transport: These constraints are typically overcome through multicellular innovations. Here, we show that an emergent biophysical mechanism{\textemdash}spontaneous fluid flows arising from metabolically generated density gradients{\textemdash}can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Beyond a threshold size, the metabolic activity of experimentally evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by ciliary actuation in extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This demonstrates how simple physical mechanisms can act as a {\textquotedblleft}biophysical scaffold{\textquotedblright} to support the evolution of multicellularity by opening up phenotypic possibilities before genetically encoded innovations.

}, doi = {DOI: 10.1126/sciadv.adr6399}, url = {https://www.science.org/doi/full/10.1126/sciadv.adr6399}, author = {NISHANT NARAYANASAMY and EMMA BINGHAM and TANNER FADERO and G. OZAN BOZDAG and WILLIAM C. RATCLIFF and PETER YUNKER and SHASHI THUTUPALLI} } @article {158510, title = {Metagenomics based longitudinal monitoring of antibiotic resistome and microbiome in the inlets of wastewater treatment plants in an Indian megacity}, year = {2025}, abstract = {

The growing threat of antimicrobial resistance (AMR) poses a significant global challenge, undermining advancements in healthcare, agriculture, and life expectancy. Despite its critical importance, data on population-level AMR trends, including seasonal and temporal variations, remain scarce. In this study, we conducted metagenomic analysis on 190 wastewater samples collected monthly from December 2022 to December 2023 in Pune, India, to assess the diversity, dynamics, and co-occurrence of AMR determinants. Using nanopore shotgun sequencing, we generated 87.86 Gbp of data, enabling the taxonomic classification of 157 bacterial phyla and 3291 genera. Proteobacteria dominated the microbial community, with notable seasonal shifts, including increased Streptococcus abundance correlating with SARS-CoV-2 viral surges in March 2023. We identified 637 distinct antimicrobial resistance genes (ARGs) associated with 29 antibiotic classes, with multidrug, macrolide-lincosamide-streptogramin, beta-lactams, and tetracyclines genes being the most prevalent, particularly within WHO priority pathogens such as\ Enterobacteriaceae\ and\ Pseudomonas. Temporal normalization of ARG abundance revealed significant seasonal variability, peaking during winter, potentially driven by increased antibiotic use for respiratory infections. The integration of viral load data with AMR trends highlighted complex interactions between viral outbreaks and AMR dissemination. This study demonstrates the potential of wastewater surveillance as an early warning system for AMR, providing valuable insights into environmental and community resistance dynamics. Our results underscore the importance of integrated AMR surveillance to inform public health strategies aimed at mitigating the global AMR threat.

}, doi = {https://doi.org/10.1016/j.scitotenv.2025.179691}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0048969725013324}, author = {Vinay Rajput and Rinka Pramanik and Kiran Nannaware and Priyanki Shah and Asim Bhalerao and Nidhi Jain and L.S. Shashidhara and Sanjay Kamble and Syed Dastager and Mahesh Dharne} } @article {162676, title = {Mitochondrial structure and function in OCRL depleted cells.}, journal = {Front Cell Dev Biol}, volume = {13}, year = {2025}, month = {2025}, pages = {1679675}, abstract = {

Lowe syndrome (LS) is an X-linked, recessive disease with a characteristic clinical triad of eye, brain, and kidney defects. LS results from mutations in the gene that encodes for inositol polyphosphate 5-phosphatase enzyme. The OCRL protein has been localized to multiple subcellular organelles including the plasma membrane and endo-lysosomal system, but the relevance of these to disease phenotypes is unclear. Previous studies have reported severe hypotonia at birth in LS patients along with structural changes in the mitochondria in muscle biopsies. These mitochondrial changes have been proposed to be secondary to renal tubular acidosis seen in LS patients. In this study, we find that neural stem cells and neurons differentiated from OCRL-depleted induced pluripotent stem cells (iPSCs) show mild defects in mitochondrial structure and function, whereas such defects are not seen in the iPSCs themselves. These mitochondrial phenotypes in neural stem cells and neurons were associated with modest changes in the mitochondrial transcriptome. Overall, our results indicate that loss of OCRL leads to mild cell autonomous defects in mitochondrial structure and function that is cell type-dependent.

}, issn = {2296-634X}, doi = {10.3389/fcell.2025.1679675}, author = {Philip, Ron George and Bhatia, Priyanka and Sharma, Yojet and Raghu, Padinjat} } @article {154274, title = {Molecular determinants of Neu5Ac binding to a tripartite ATP independent periplasmic (TRAP) transporter}, year = {2025}, abstract = {
N -Acetylneuraminic acid (Neu5Ac) is a negatively charged nine-carbon amino sugar that is often the peripheral sugar in human cell-surface glycoconjugates. Some bacteria scavenge, import, and metabolize Neu5Ac or redeploy it on their cell surfaces for immune evasion. The import of Neu5Ac by many bacteria is mediated by tripartite ATP-independent periplasmic (TRAP) transporters. We have previously reported the structures of SiaQM, a membrane-embedded component of the Haemophilus influenzae TRAP transport system, (Currie et al., 2024). However, none of the published structures contain Neu5Ac bound to SiaQM. This information is critical for defining the transport mechanism and for further structure-activity relationship studies. Here, we report the structures of Fusobacterium nucleatum SiaQM with and without Neu5Ac. Both structures are in an inward (cytoplasmic side) facing conformation. The Neu5Ac-bound structure reveals the interactions of Neu5Ac with the transporter and its relationship with the Na+ binding sites. Two of the Na+-binding sites are similar to those described previously. We identify a third metal-binding site that is further away and buried in the elevator domain. Ser300 and Ser345 interact with the C1-carboxylate group of Neu5Ac. Proteoliposome-based transport assays showed that Ser300-Neu5Ac interaction is critical for transport, whereas Ser345 is dispensable. Neu5Ac primarily interacts with residues in the elevator domain of the protein, thereby supporting the elevator with an operator mechanism. The residues interacting with Neu5Ac are conserved, providing fundamental information required to design inhibitors against this class of proteins.
}, doi = {10.7554/eLife.98158}, author = {Parveen Goyal and KanagaVijayan Dhanabalan and Mariafrancesca Scalise and Rosmarie Friemann and Cesare Indiveri and Renwick C J Dobson and Kutti R Vinothkumar and Subramanian Ramaswamy} } @article {160488, title = {Monitoring Protein Deamidation in Real Time Using NMR.}, journal = {Magn Reson Chem}, year = {2025}, month = {2025 Sep 18}, abstract = {

Deamidation, a modification of glutamine residues in host proteins, plays a key role in bacterial pathogenesis, where bacterial effectors manipulate host signaling pathways by modifying proteins like ubiquitin (Ub) and Ub-like protein NEDD8. The study uses traditional and real-time NMR-based techniques to investigate the enzymatic activity of two bacterial deamidases, cycle inhibitory factors, CIF from Escherichia coli and CIF from Burkholderia pseudomallei. We employed BEST-HSQC NMR spectroscopy to monitor real-time deamidation of ubiquitin, providing a robust and efficient method for quantifying enzyme activity. Our findings highlight significant differences in catalytic efficiency between CIF and CIF, despite their structural similarities. NMR-based rate measurements show CIF has higher catalytic efficiency than CIF, consistent with the previous reports, while kinetic analysis of CIF indicates relatively weak substrate binding and suboptimal efficiency, suggesting a potential regulatory role during infections. While the overall globular fold of the ubiquitin remains unchanged upon deamidation, we observed changes in the local chemical environment, suggesting potential localized structural changes. This study extends the use of NMR spectroscopy to investigate irreversible posttranslational modifications (PTMs) like deamidation, offering a valuable tool for understanding the molecular mechanisms behind bacterial manipulation of host cellular processes.

}, issn = {1097-458X}, doi = {10.1002/mrc.70045}, author = {Agrata, Rashmi and Das, Ranabir} } @article {152168, title = {Motor Function of the Two-Component EEA1-Rab5 Revealed by dcFCCS.}, journal = {Methods Mol Biol}, volume = {2881}, year = {2025}, month = {2025}, pages = {87-115}, abstract = {

Fluorescence correlation spectroscopy (FCS) enables the measurement of fluctuations at fast timescales (typically few nanoseconds) and with high spatial resolution (tens of nanometers). This single-molecule measurement has been used to characterize single-molecule transport and flexibility of polymers and biomolecules such as DNA and RNA. Here, we apply this technique as dual-color fluorescence cross-correlation spectroscopy (dcFCCS) to identify the motor function of the tethering protein EEA1 and the small GTPase Rab5 by probing the flexibility changes through end-monomer fluctuations.

}, keywords = {Humans, rab5 GTP-Binding Proteins, Single Molecule Imaging, Spectrometry, Fluorescence, Vesicular Transport Proteins}, issn = {1940-6029}, doi = {10.1007/978-1-0716-4280-1_4}, author = {Soler, Joan Antoni and Singh, Anupam and Zerial, Marino and Thutupalli, Shashi} } @article {161130, title = {The multifaceted phosphatidylinositol 5 phosphate 4-kinase proteins: molecular properties and biological functions.}, journal = {Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids}, volume = {1871}, year = {2025}, type = {2025 Oct 21}, abstract = {

Phosphoinositides are regulators of key cell biological processes such as plasma membrane function, vesicular transport, cytoskeletal and nuclear organization. In turn, their levels are tightly controlled by the function of lipid kinases and phosphatases that modify specific hydroxyl groups on the inositol ring. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is one such lipid kinase. Although initially discovered as an enzyme that phosphorylates the 4th hydroxyl on the inositol ring of phosphatidylinositol 5 phosphate (PI5P) with exquisite specificity, it has recently emerged that PIP4K may also work on other substrates. Interestingly, recent studies have also proposed functions for this enzyme that do not require its catalytic activity. Although most elements of phosphoinositide signalling are conserved across all eukaryota, a limited number of phosphoinositide kinases and phosphatases including PIP4K seem to be a unique feature of the genomes of organisms that exist in a multicellular state but not unicellular eukaryotes. Genetic studies in model organisms implicate PIP4K function in key processes such as hormone regulated metabolic control as well as cell division and growth. Consequently, PIP4K function has important biomedical implications in the context of cancer, metabolic syndrome and autoimmune disorders. In this review, we analyze emerging findings on PIP4K function and reflect on the biochemical\ raison d{\textquoteright}{\^e}tre\ of how this protein regulates cell physiology in metazoans.

}, keywords = {PhosphoinositidesEnzymesPIP4KLipid signallingDisease biologyCellular organization}, doi = {https://doi.org/10.1016/j.bbalip.2025.159698}, author = {Krishnan, H{\textquoteright} and Venugopal, A{\textquoteright} and Alex, P{\textquoteright} and Raghu, P{\textquoteright}} } @article {152166, title = {Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.}, journal = {Biophys J}, volume = {124}, year = {2025}, month = {2024 Dec 13}, pages = {393-407}, abstract = {

NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length NOTCH and its ligands remain poorly understood. In this study, we employed fragment-based modeling and multiscale simulations to study the full-length structure of the human NOTCH ectodomain, comprising 1756 amino acids. We performed coarse-grained dynamics simulations of NOTCH in both glycosylated and nonglycosylated forms to investigate the role\ of\ glycosylation in modulating its conformational dynamics. In apo form, coarse-grained simulations revealed that glycosylated NOTCH protein can transition from an elongated structure of \~{}86\ nm from the membrane surface to a semicompact state (\~{}23.81 {\textpm} 9.98\ nm), which aligns with cryo-EM data. To transition from the apo form to ligand-bound forms of NOTCH, we followed an atomistic and integrative modeling approach to model the interactions between NOTCH-DLL4 and NOTCH-JAG1. Atomistic simulations of the smaller bound fragment EGF8-13 patch revealed conformational plasticity critical for NOTCH binding, while integrative modeling of full-length complexes suggested a larger binding surface than reported previously. Simulations of pathogenic mutations revealed that E360K and R448Q disrupted the NOTCH-ligand interaction surfaces, causing dissociation. In contrast, C1133Y in the Abruptex domain compromised protein stability by disrupting the domain{\textquoteright}s interaction with the ligand-binding domain in the apo form of NOTCH-ECD. These findings provide a detailed molecular understanding of NOTCH and its ligands, offering insights that could enable the development of novel therapeutic approaches to selectively target pathogenic NOTCH signaling.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2024.12.014}, author = {Rathore, Surabhi and Gahlot, Deepanshi and Castin, Jesu and Pandey, Arastu and Arvindekar, Shreyas and Viswanath, Shruthi and Thukral, Lipi} } @article {158954, title = {Mutation bias alters the distribution of fitness effects of mutations.}, journal = {PLoS Biology}, year = {2025}, abstract = {

Mutation bias is an important factor determining the diversity of genetic variants available for selection. As adaptation proceeds and some beneficial mutations are fixed, new beneficial mutations become rare, limiting further adaptation. The depletion of beneficial mutations is especially stark within the mutational class favored by the existing mutation bias. Recent theoretical work predicts that this problem may be alleviated by a change in the direction of mutation bias (i.e., a bias reversal). If populations sample previously underexplored types of mutations, the distribution of fitness effects (DFE) of mutations should shift towards more beneficial mutations. Here, we test this prediction using\ Escherichia coli, which has a transition mutation bias, with ~54\% single-nucleotide mutations being transitions compared to the unbiased expectation of ~33\% transitions. We generated mutant strains with a wide range of mutation biases, from 97\% transitions to 98\% transversions, either reinforcing or reversing the wild-type transition bias. Quantifying DFEs of ~100 single mutations obtained from mutation accumulation experiments for each strain, we find strong support for the theoretical prediction. Strains that oppose the ancestral bias (i.e., with a strong transversion bias) have DFEs with the highest proportion of beneficial mutations, whereas strains that exacerbate the ancestral transition bias have up to 10-fold fewer beneficial mutations. Such dramatic differences in the DFE should drive large variation in the rate and outcome of adaptation, suggesting an important and generalized evolutionary role for mutation bias shifts.

}, doi = {10.1371/journal.pbio.3003282}, author = {Sane, M and Parveen, S and Agashe, D} } @article {152903, title = {Natural and sexual selection and functional roles influence colouration but not the amount of variation in butterfly wing colour patterns.}, journal = {BMC Ecol Evol}, volume = {25}, year = {2025}, month = {2025 Jan 17}, pages = {11}, abstract = {

BACKGROUND: Trait variation is shaped by functional roles of traits and the strength and direction of selection acting on the traits. We hypothesized that in butterflies, sexually selected colouration is more variable owing to condition-dependent nature and directional selection on sexual ornaments, whereas naturally selected colouration may be less variable because of stabilising selection. We measured reflectance spectra, and extracted colour parameters, to compare the amount of variation in sexually versus naturally selected colour patches across wing surfaces and sexes of 20 butterfly species across 4 families (Nymphalidae, Papilionidae, Pieridae, Lycaenidae).

RESULTS: We found that: (a) males had more conspicuous, i.e., brighter and more saturated colour patches compared with females (as expected of sexually selected traits but not necessarily of naturally selected traits), and (b) dorsal surfaces in both sexes had more conspicuous sexual ornaments as well as protective (aposematic/mimetic) colour patches on darker wing backgrounds, compared with ventral surfaces. However, colour patches did not differ in the amount of variation either in selection (ecological/sexual functions), sex or wing surface-specific manner.

CONCLUSIONS: These findings show that functional roles and selection influence colour parameters but not the amount of variation in butterfly wing colour patterns.

}, keywords = {Animals, Butterflies, Color, Female, Male, Pigmentation, Selection, Genetic, Sex Characteristics, Sexual Selection, Wings, Animal}, issn = {2730-7182}, doi = {10.1186/s12862-024-02346-8}, author = {Dharmaraaj, Bhavya and Kunte, Krushnamegh} } @article {157494, title = {A New Discrete-Geometry Approach for Integrative Docking of Proteins Using Chemical Cross-Links}, journal = {Journal of Chemical Information and Modeling}, volume = {65}, year = {2025}, month = {29 April 2025}, pages = {44576-4592}, chapter = {4576}, abstract = {

The structures of protein complexes allow us to understand and modulate the biological functions of the proteins. Integrative docking is a computational method to obtain the structures of a protein complex, given the atomic structures of the constituent proteins along with other experimental data on the complex, such as chemical cross-links or SAXS profiles. Here, we develop a new discrete geometry-based method, wall-EASAL, for integrative rigid docking of protein pairs given the structures of the constituent proteins and chemical cross-links. The method is an adaptation of efficient atlasing and search of assembly landscapes (EASAL), a state-of-the-art discrete geometry method for efficient and exhaustive sampling of macromolecular configurations under pairwise intermolecular distance constraints. We provide a mathematical proof that the method finds a structure satisfying the cross-link constraints under a natural condition satisfied by energy landscapes. We compare wall-EASAL with integrative modeling platform (IMP), a commonly used integrative modeling method, on a benchmark, varying the numbers, types, and sources of input cross-links, and sources of monomer structures. The wall-EASAL method performs similarly to IMP in terms of the average satisfaction of the configurations to the input cross-links and the average similarity of the configurations to their corresponding native structures. But wall-EASAL is more efficient than IMP and more robust against false positive cross-links in the context of binary integrative rigid docking. Although the current study uses cross-links, the method is general and any source of distance constraints can be used for integrative docking with wall-EASAL. However, the current implementation only supports binary rigid protein docking, i.e., assumes that the monomer structures are known and remain rigid. Additionally, the current implementation is deterministic, i.e., it does not account for some uncertainties in the cross-linking data, such as noise in the cross-link distances. Neither of these appears to be a theoretical or algorithmic limitation of the EASAL methodology. Structures from wall-EASAL can be incorporated in methods for modeling large macromolecular assemblies, for example by suggesting rigid bodies or restraints for use in these methods. This will facilitate the characterization of assemblies and cellular neighborhoods at increased efficiency, accuracy, and precision

}, doi = {https://doi.org/10.1021/acs.jcim.4c02412}, url = {https://pubs.acs.org/doi/full/10.1021/acs.jcim.4c02412}, author = {Yichi Zhang and Muskaan Jindal and Shruthi Viswanath and Meera Sitharam} } @article {157421, title = {Nonequilibrium asymmetry in the living cell membrane.}, journal = {Faraday Discuss}, year = {2025}, month = {2025 May 08}, abstract = {

We will discuss how sustained nonequilibrium processes operating at the plasma membrane (PM) determine the dynamical organisation (both lateral and transverse) of lipids, their maintenance and control, under physiological conditions. These nonequilibrium processes include active contractile stresses arising from the inevitable interaction of the inner leaflet of the PM with the adjoining actomyosin cortex, and active flipping of specific lipids. Recently, we showed that the inner leaflet phosphatidylserine (PS) interacts with the actomyosin cortex and engages in a strong transbilayer coupling across the leaflets. Here we develop an active Flory-Huggins theory for the mesoscale segregation of liquid-ordered (lo)-liquid-disordered (ld) domains in an asymmetric membrane bilayer, that incorporates both active contractile stresses at the inner leaflet and transbilayer coupling across the leaflets. The interplay between chemical potential gradients, transbilayer coupling and active stresses drives a rich pattern of mesoscale lo domains - static, strongly fluctuating and moving active emulsions - even at temperatures beyond the equilibrium phase transition temperature. We study conditions under which domain registry and slippage could be observed. We end with a discussion on the role of active flippases on PS in maintaining the active mesoscale organisation.

}, issn = {1364-5498}, doi = {10.1039/d4fd00207e}, url = {https://pubmed.ncbi.nlm.nih.gov/40338126/}, author = {Bansal, Ajay Kumar and Rao, Madan} } @article {152152, title = {NSD3 protein methylation and stabilization transforms human ES cells into variant state.}, journal = {Life Sci Alliance}, volume = {8}, year = {2025}, month = {2025 Mar}, abstract = {

Cultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas. Furthermore, we discovered an altered epigenomic landscape and overexpression of the lysine methyltransferases EHMT1, EHMT2, and NSD group of proteins in vhESCs. Remarkably, depleting NSD3 oncogene reversed the molecular and phenotypic changes in vhESCs. We identified a detailed mechanism where EHMT2 interacts and methylates NSD3 at lysine 477, stabilizing its protein levels in vhESCs. In addition, we showed that NSD3 levels are regulated by protein degradation in hESCs, and its stabilization leads to the emergence of the variant state. Overall, our study identify that misregulation of NSD3 in pluripotent stem cells, through methylation-mediated abrogation of its protein degradation, drives hESCs towards oncogenic transformation.

}, keywords = {Cell Differentiation, Cell Line, Cell Transformation, Neoplastic, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Histone-Lysine N-Methyltransferase, Human Embryonic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Methylation, Nuclear Proteins, Pluripotent Stem Cells, Protein Stability, Repressor Proteins}, issn = {2575-1077}, doi = {10.26508/lsa.202402871}, author = {Krishnamoorthy, Vignesh K and Hamdani, Fariha and Shukla, Pooja and Rao, Radhika Arasala and Anaitullah, Shaikh and Biligiri, Kriti Kestur and Kadumuri, Rajashekar Varma and Pothula, Purushotham Reddy and Chavali, Sreenivas and Rampalli, Shravanti} } @article {155542, title = {Open letter: There are more than just trees and forests to be conserved and restored}, year = {2025}, publisher = {Plants, People, Planet}, abstract = {

Tropical and subtropical grasslands and savannas have historically been neglected in global and local conservation policies. As a result, nearly half of their coverage has been lost. In 2023, the world{\textquoteright}s most biodiverse savanna (Brazilian Cerrado) lost 1.110.326 ha, increasing the rate of land conversion by 67.7\% (MapBiomas,\ 2024). The resulting biodiversity and ecosystem service losses, including the ability to mitigate climate change, are profound and irreversible.

As scientists specialized in ecology, conservation, and restoration, from around the world, we call on policymakers at COP 16 to act decisively:\ Tropical and subtropical grasslands and savannas matter for biodiversity protection, and the future of this planet relies on these ecosystems to the same extent it relies on forests.

We urge the following commitments:

}, doi = {https://doi.org/10.1002/ppp3.10635}, url = {https://nph.onlinelibrary.wiley.com/doi/10.1002/ppp3.10635}, author = {Natashi Pilon and Franciele Peixoto and Jayashree Ratnam and Mahesh Sankaran} } @article {162678, title = {Organization principles of dynamic three-dimensional genome architecture associated with centromere clustering states.}, journal = {Proc Natl Acad Sci U S A}, volume = {122}, year = {2025}, month = {2025 Dec 16}, pages = {e2520310122}, abstract = {

Fungal centromeres are clustered near microtubule organizing centers to help adopt the Rabl chromosomal organization. The role of centromere clustering in driving large-scale changes in structural and functional chromatin assembly remains unclear. Here, using Hi-C and superresolution microscopy, we show that cell cycle-dependent centromere declustering and clustering states in drive global changes in the 3D genome architecture. Centromeres and telomeres are scattered around the nuclear periphery at interphase, and this arrangement constrains the interarm interactions within a chromosome, providing a unique interphase chromosome organization. Moreover, centromeres and telomeres are organized as separate compartments, segregating them from active euchromatic regions. Polymer modeling reveals that the transition from the unclustered to clustered centromere state during the cell cycle involves changes from a globular to an elongated chromosome architecture. Strikingly, while clustered centromeric regions replicate early in most yeasts, centromeres replicate late in S-phase, hinting at a possible link between centromere clustering dynamics and DNA replication timing. Overall, our study uncovers several unique organizational principles governing the dynamic genome architecture in an evolutionarily diverged basidiomycete yeast.

}, keywords = {Cell Cycle, Centromere, Chromosomes, Fungal, Cryptococcus neoformans, Genome, Fungal, Telomere}, issn = {1091-6490}, doi = {10.1073/pnas.2520310122}, author = {Polisetty, Satya Dev and Dutta, Shuvadip and Vadnala, Rakesh Netha and Notani, Dimple and Padinhateeri, Ranjith and Sanyal, Kaustuv} } @article {156921, title = {An Oryza-specific histone H4 variant predisposes H4 lysine 5 acetylation to modulate salt stress responses}, year = {2025}, abstract = {
Paralogous variants of canonical histones guide accessibility to DNA and function as additional layers of genome regulation. Across eukaryotes, the mechanism of action and functional significance of several variants of core histones are well known except those of histone H4. Here we show that a variant of H4 (H4.V) expressing tissue-specifically among Oryza members mediated specific epigenetic changes contributing to salt tolerance. H4.V was incorporated into specific heterochromatic sites, where it blocked the deposition of active histone marks. Stress-dependent redistribution of H4.V enabled the incorporation of acetylated H4 lysine 5 (H4K5ac) in the gene bodies. The misexpression of H4.V led to defects in reproductive development and in mounting salt stress responses. H4.V formed homotypic nucleosomes and mediated these alterations by conferring distinct molecular properties to the nucleosomes, as seen with cryo electron microscopy structures and biochemical assays. These results reveal not only an H4 variant among plants but also a chromatin regulation that might have contributed to the adaptation of semi-aquatic Oryza members.
}, doi = {10.1038/s41477-025-01974-2}, author = {Vivek Hari Sundar Gandhivel and Paula Sotelo-Parrilla and Steffi Raju and Shaileshanand Jha and Anjitha Gireesh and Chitthavalli Y. Harshith and Fabian Gut and Kutti R. Vinothkumar and Fr{\'e}d{\'e}ric Berger and A. Arockia Jeyaprakash and Shivaprasad, P V} } @article {160480, title = {OsWRKY53 dictates wound responses in rice through fine-tuning crosstalk between PEP and PSK-mediated signalling.}, journal = {Plant J}, volume = {123}, year = {2025}, month = {2025 Sep}, pages = {e70481}, abstract = {

Wounding is a major event during the multitude of stresses that plants face in their natural environment. Wound response is very dynamic and involves the integration of various regulatory networks culminating in successful wound-induced downstream signalling. Plants depend on endogenous molecular signals predominantly, small peptides, to initiate wound responses. Transcriptional response is paramount in dictating a successful wound response. Here we show the involvement of a WRKY transcription factor (TF) named OsWRKY53 that is upregulated upon wounding as well as wound-derived plant elicitor peptide (PEP), OsPep2 treatments. OsWRKY53 is involved in the positive regulation of gene expression of OsPep2-responsive genes. OsWRKY53 displays altered DNA occupancy in response to OsPep2 treatment over time, correlating with the altered gene expression. OsWRKY53 undergoes phosphorylation upon OsPep2 perception, and this contributes to the enhanced stability of the protein. Further, OsWRKY53 is involved in the simultaneous activation and suppression of OsPep2-responsive and phytosulfokine (PSK)-responsive genes, respectively. In agreement with these findings, perturbed expression of OsWRKY53 leads to compromised transcriptional responses post-wounding. Collectively, we establish that OsWRKY53 acts at the intersection of PEP and PSK-mediated transition of wound responses.

}, keywords = {Gene Expression Regulation, Plant, Oryza, Phosphorylation, Plant Proteins, Signal Transduction, Transcription Factors}, issn = {1365-313X}, doi = {10.1111/tpj.70481}, author = {Harshith, Chitthavalli Y and Palchaudhuri, Dipasmit and Dey, Riju and Raju, Steffi and Shivaprasad, Padubidri V} } @article {158957, title = {Outside influences: The impact of extracellular matrix mechanics on cell migration.}, journal = {Curr Top Dev Biol}, volume = {164}, year = {2025}, month = {2025}, pages = {29-65}, abstract = {

"No cell is an island" - highlights the interconnectedness of cellular behavior and the extracellular matrix (ECM). Cell migration is inherently contextual, as cells navigate and adapt to their environments, reshaping the ECM while being influenced by its properties. This review focuses on the mechanical characteristics of the ECM-specifically its architecture, porosity, dynamics, and stiffness-and how these attributes affect cell behavior and migration strategies. We discuss how the mechanical properties are modulated by the composition and arrangement of ECM components and the role of enzymatic activities, including crosslinking and matrix metalloproteinases. By presenting examples from vertebrate and invertebrate developmental models, we demonstrate how ECM mechanics dictate cell migration at various biological scales. Additionally, we examine the importance of cell-matrix adhesions in regulating migration speed and direction. While in vitro studies have advanced our understanding of the molecular mechanisms at play, significant questions persist regarding the regulation of cell migration by ECM mechanics in vivo. Ultimately, this synthesis aims to illuminate the complexities of cell-ECM mechanical interactions, pointing the way for future research that may unveil novel insights into how ECM mechanics influences cell migration during development and disease.

}, keywords = {Animals, Biomechanical Phenomena, Cell Adhesion, Cell Movement, Extracellular Matrix, Humans}, issn = {1557-8933}, doi = {10.1016/bs.ctdb.2025.01.003}, author = {Zaidel-Bar, Ronen and Agarwal, Priti} } @article {161134, title = {The patterning and proliferation roles of Shh are partitioned on distinct exosomes.}, journal = {Dev Biol}, volume = {528}, year = {2025}, month = {2025 Dec}, pages = {239-254}, abstract = {

Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened-Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened-Gαi-dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.

}, keywords = {Animals, Body Patterning, Cell Proliferation, Exosomes, Gene Expression Regulation, Developmental, Hedgehog Proteins, Mice, Neural Tube, Notochord, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins, Signal Transduction, Smoothened Receptor, Spinal Cord, Zinc Finger Protein GLI1}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2025.09.017}, author = {Walvekar, Ankita and Pandey, Shivangi and Kamat, Siddhesh S and Ladher, Raj K and Vyas, Neha} } @article {161318, title = {Paused RNA polymerase primes promoters via RNA-mediated stabilisation of transcription factor ERα.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Oct 29}, pages = {9553}, abstract = {

Regulated pausing of RNA polymerase II (Pol II) is essential for enabling rapid and coordinated transcriptional responses to signalling cues.\ Pausing also contributes to the formation of nucleosome-free regions with the help of chromatin remodellers. However, if these nucleosome-free regions engage with transcription factors to stimulate the transcription potential of paused promoters is not known. In this study, we demonstrate that ligand-induced estrogen receptor-alpha (ERα) binding is stabilized at Pol II-paused sites. This stabilization results from an increased dwell time of ERα on chromatin, as revealed by single molecule tracking (SMT) experiments. Notably, short chromatin-associated RNAs generated by the paused Pol II contribute to enhancing ERα binding at paused promoters. We also observe that pausing increases H3K27ac levels, which primes paused promoters for robust transcriptional activation upon release. Collectively, these findings suggest that paused Pol II plays a central role in enhancing transcription factor binding through an RNA-dependent mechanism. This, in turn, results in a more vigorous transcriptional response following pausing release, thus contributing to the fine-tuning of ERα-mediated gene regulation.

}, keywords = {Chromatin, Estrogen Receptor alpha, Histones, Humans, Nucleosomes, Promoter Regions, Genetic, Protein Binding, RNA, RNA Polymerase II, Transcription, Genetic, Transcriptional Activation}, issn = {2041-1723}, doi = {10.1038/s41467-025-64569-7}, author = {Mann, Rajat and Soota, Deepanshu and Das, Ayan and Podh, Nitesh Kumar and Mehta, Gunjan and Notani, Dimple} } @article {159722, title = {Phosphoinositide acyl chain diversity: comparative analysis across species and mouse tissues.}, journal = {Biochim Biophys Acta Mol Cell Biol Lipids}, volume = {1870}, year = {2025}, month = {2025 Aug}, pages = {159640}, abstract = {

Cells create acyl chain compositions for their phosphoinositide (PIPn) pools that are distinct from other phospholipid classes. While some lower eukaryotes present highly heterogeneous PIPn (e.g., yeast, fly), more complex organisms typically display PIPn enriched in fewer molecular species (e.g., the C38:4 species in fish, frog and mice). A comprehensive analysis of murine tissues (using both LC-MS/MS and MSI) confirms a general enrichment for C38:4-PIPn but also highlights the existence of several cell populations with strikingly divergent acyl chain compositions, characterised by the prevalence of shorter-chain, more saturated species (e.g., C32:0 in the testes and C34:1 in the prostate). The evolutionary pressures driving the creation of these specific acyl chain compositions are still unclear; current evidence suggests there is probably a balance to be achieved in different cell types between the biophysical constraints imposed by PIPn as membrane-captive {\textquoteright}messengers{\textquoteright} (e.g., flexibility in head group presentation in different membrane environments), the demand for substantial de novo lipid synthesis (e.g., in rapid membrane expansion), the need for acyl chain remodelling (e.g., in molecular segregation of functional pools) and fatty acid availability. Moreover, it would appear inevitable that this balance will be distorted under most cell culture conditions in vitro.

}, keywords = {Animals, Male, Mice, Phosphatidylinositols, Species Specificity, Tandem Mass Spectrometry}, issn = {1879-2618}, doi = {10.1016/j.bbalip.2025.159640}, author = {Barneda, David and Janardan, Vishnu and Swales, John and Ciaccia, Maria and Goodwin, Richard and Cosulich, Sabina and Raghu, Padinjat and Clark, Jonathan and Stephens, Len and Hawkins, Phillip} } @article {158513, title = {Phosphoinositide acyl chain diversity: comparative analysis across species and mouse tissues}, year = {2025}, abstract = {

Cells create acyl chain compositions for their phosphoinositide (PIPn) pools that are distinct from other phospholipid classes. While some lower eukaryotes present highly heterogeneous PIPn (e.g., yeast, fly), more complex organisms typically display PIPn enriched in fewer molecular species (e.g., the C38:4 species in fish, frog and mice). A comprehensive analysis of murine tissues (using both LC-MS/MS and MSI) confirms a general enrichment for C38:4-PIPn but also highlights the existence of several cell populations with strikingly divergent acyl chain compositions, characterised by the prevalence of shorter-chain, more saturated species (e.g., C32:0 in the testes and C34:1 in the prostate). The evolutionary pressures driving the creation of these specific acyl chain compositions are still unclear; current evidence suggests there is probably a balance to be achieved in different cell types between the biophysical constraints imposed by PIPn as membrane-captive {\textquoteleft}messengers{\textquoteright} (e.g., flexibility in head group presentation in different membrane environments), the demand for substantial de novo lipid synthesis (e.g., in rapid membrane expansion), the need for acyl chain remodelling (e.g., in molecular segregation of functional pools) and fatty acid availability. Moreover, it would appear inevitable that this balance will be distorted under most cell culture conditions in vitro.

}, keywords = {PhosphoinositidePIAcyl chainC38:4LYCATLPIAT1MBOAT7MSILC-MSProstateTestes}, doi = {https://doi.org/10.1016/j.bbalip.2025.159640}, url = {https://www.sciencedirect.com/science/article/pii/S1388198125000484}, author = {David Barneda and Vishnu Janardan and John Swales and Maria Ciaccia and Richard Goodwin and Sabina Cosulich and Padinjat Raghu and Jonathan Clark and Len Stephens and Phillip Hawkins} } @article {159718, title = {The Pioneering Legacy of Veronica Rodrigues in Drosophila Neurobiology}, journal = {Resonance }, volume = {30, pages 1055{\textendash}1075}, year = {2025}, month = {18-08-2025}, type = {Research}, author = {K, VijyaRaghavan} } @article {158515, title = {Poles Apart: The Structure and Composition of the Bird Community in Bamboo in the Eastern Himalaya}, year = {2025}, abstract = {

Bamboo is a unique, dynamic, and diverse group of plants shown to harbor communities of obligate specialists. Such phenomena, however, have primarily been investigated in the Neotropics. Additionally, mechanisms underlying specialist bamboo communities are generally poorly understood. By studying bird and arthropod communities across two seasons in bamboo and adjacent rainforest in the Eastern Himalaya, we provide some of the first systematic evidence of bamboo-specialist communities. We show that arthropod communities differ significantly between habitats and across seasons and that bamboo-specialist birds likely feed on distinct arthropods within bamboo sheaths using specialized bills and unique foraging behaviors in this part of the world. We hypothesize that this bird-bamboo association could be driven by a dietary specialization to the unique arthropods in bamboo. These results contribute to our understanding of how species can specialize on temporally dynamic resources and highlight the need for more research on such lesser-known habitats.

}, doi = {https://doi.org/10.1086/735417 }, url = {https://www.journals.uchicago.edu/doi/abs/10.1086/735417}, author = {Sidharth Srinivasan and Dambar Kumar Pradhan and Shambu Rai and Aman Biswakarma and Umesh Srinivasan} } @article {158948, title = {Precise identification of viral-host integration events in HPV-positive cervical cancers by targeted long-read sequencing.}, journal = {Tumour Virus Res}, volume = {20}, year = {2025}, month = {2025 Jul 17}, pages = {200325}, abstract = {

Human papillomaviral (HPV) integrations into host human genome, a frequently observed event in HPV associated cervical cancer, are currently mapped through expensive Whole Genome sequencing (WGS) or RNA sequencing (RNA-seq) methodologies. This study aims to develop a targeted sequencing assay to determine HPV integrations in cervical tumors without the need for WGS or RNA-seq. We employed a library preparation strategy using tiled single primers that bind to HPV genome as a template and possibly extend HPV sequences into adjacent host human genomic sequences resulting in HPV and human chimeric sequences. Using this strategy, we sequenced known HPV integrations in HPV18 positive HeLa and HPV16 positive SiHa cell lines. We further used this method to detect HPV integration sites in four HPV-positive cervical cancer patients and confirmed these integration breakpoints by WGS and Sanger sequencing. Functional impact of HPV integrations was explored through differentially expressed genes within or near topologically associating domain (TAD) boundaries, possibly disrupted by respective integration events in these patients. We found ZFP36L1, CPA3, CPB1 and CXCL8 as some of the differentially expressed genes within disrupted TADs, which are known cancer associated genes. Our approach also reduced the cost of HPV integration detection by 90\ \% compared to WGS while also minimizing sequencing data volume. We believe that this method captures HPV integrations at significantly reduced costs and lesser sequencing data volume leading to better understanding of disease progression and monitoring cancer treatment.

}, issn = {2666-6790}, doi = {10.1016/j.tvr.2025.200325}, author = {Parida, Preetiparna and Mukherjee, Nivedita and Singh, Agastya and Lewis, Shirley and Sharan, Krishna and Mallya, Sandeep and Singh, Ashima and Das, Surya Sarathi and Rao, Mahadev and Higginson, Daniel S and Sabarinathan, Radhakrishnan and Damerla, Rama Rao} } @article {159716, title = {Presence of large trees and tree diversity enhances carbon storage in the Western Ghats.}, journal = {Biological Conservation}, volume = {308}, year = {2025}, month = {01-08-2025}, abstract = {

Tropical forests\ are highly diverse ecosystems with significant\ carbon sequestration\ potential. Above-ground biomass (AGB) represents a key carbon pool in these forests. We estimated AGB along with diversity, structural, and environmental attributes, from eight one-hectare permanent plots in the tropical forests of the\ Western Ghats, India. The relationships between these attributes and biomass were assessed. Shannon diversity (Pearson{\textquoteright}s\ r\ =\ 0.63), mean diameter at breast height (DBH) (r\ =\ 0.99), and total\ basal area\ (r\ =\ 0.76) showed positive correlations with AGB. The AGB value ranged between 228.6 and 746.8\ Mg/ha, while species richness varied between 47 and 95\ ha-1. Large\ woody plants\ (DBH\ >=\ 60\ cm) had the highest contribution (5.9{\textendash}62.13\ \%) to AGB despite their low prevalence (0.18{\textendash}3.14\ \%). AGB also showed strong positive correlations with large tree definitions (r = 0.70 - 0.82), highlighting their crucial role in carbon storage. These findings highlight that conserving large trees and maintaining\ species diversity\ is critical for sustaining carbon stocks, underlining the need for targeted forest management strategies that enhance both biodiversity and climate mitigation outcomes.

}, keywords = {Tropical forestPermanent plotsAbove ground biomassDiversityLarge woody plantsWestern Ghats}, doi = {DOI: https://doi.org/10.1016/j.biocon.2025.111250}, author = {{\textquoteright}Nasla, Najeeb{\textquoteright} and {\textquoteright}Karun, Jose{\textquoteright}, and {\textquoteright}K.A., Sreejith{\textquoteright}, and {\textquoteright}Sandeep, Pulla{\textquoteright}, and {\textquoteright}H.S., Suresh{\textquoteright}, and {\textquoteright}Jayashree,. Ratnam{\textquoteright}, and {\textquoteright}H.V., Raghavendra{\textquoteright}, and {\textquoteright}Dayani., Chakravarthy{\textquoteright}, and {\textquoteright}Rajiv Kumar., Chaturvedi{\textquoteright},} } @article {157483, title = {Presence of large trees and tree diversity enhances carbon storage in the Western Ghats}, journal = {Biological Conservation}, volume = {308}, year = {2025}, month = {August 2025}, pages = {111250}, type = {Research Article}, abstract = {

Tropical forests are highly diverse ecosystems with significant carbon sequestration potential. Above-ground biomass (AGB) represents a key carbon pool in these forests. We estimated AGB along with diversity, structural, and environmental attributes, from eight one-hectare permanent plots in the tropical forests of the Western Ghats, India. The relationships between these attributes and biomass were assessed. Shannon diversity (Pearson{\textquoteright}s\ r\ =\ 0.63), mean diameter at breast height (DBH) (r\ =\ 0.99), and total basal area (r\ =\ 0.76) showed positive correlations with AGB. The AGB value ranged between 228.6 and 746.8\ Mg/ha, while species richness varied between 47 and 95\ ha-1. Large woody plants (DBH\ >=\ 60\ cm) had the highest contribution (5.9{\textendash}62.13\ \%) to AGB despite their low prevalence (0.18{\textendash}3.14\ \%). AGB also showed strong positive correlations with large tree definitions (r = 0.70 - 0.82), highlighting their crucial role in carbon storage. These findings highlight that conserving large trees and maintaining species diversity is critical for sustaining carbon stocks, underlining the need for targeted forest management strategies that enhance both biodiversity and climate mitigation outcomes.

}, doi = {https://doi.org/10.1016/j.biocon.2025.111250}, url = {https://www.sciencedirect.com/science/article/pii/S0006320725002873?dgcid=rss_sd_all}, author = {Nasla Najeeb and Karun Jose and K. A. Sreejith and Sandeep Pulla and H. S. Suresh and Jayashree Ratnam and H. V. Raghavendra and Dayani Chakravarthy and Rajiv Kumar Chaturvedi} } @article {158501, title = {The primary cilium as a gatekeeper of FGFR2 function}, year = {2025}, abstract = {

In this issue, Nita et al. (https://doi.org/10.1083/jcb.202311030) show that the primary cilium regulates FGFR2 signalling through spatial compartmentalization, enabling selective downstream activation. Disruption of ciliary localization in disease-linked FGFR2 variants highlights the role of the cilium as a signalling gatekeeper in development and disease.

}, doi = {https://doi.org/10.1083/jcb.202505022}, url = {https://rupress.org/jcb/article/224/7/e202505022/278048/The-primary-cilium-as-a-gatekeeper-of-FGFR2}, author = {Raman kaushik and Raj k. Ladher} } @article {155516, title = {Reproductive Barriers and Genomic Hotspots of Adaptation During Allopatric Species Divergence.}, journal = {Mol Ecol}, year = {2025}, month = {2025 Mar 04}, pages = {e17703}, abstract = {

Theory predicts that in allopatric populations, genomic divergence and reproductive barriers may be driven by random genetic drift and thereby evolve slowly in large populations. However, local adaptation and divergence under selection may also play important roles, which remain poorly characterised. Here, we address three key questions in young allopatric species: (a) How widespread are genomic signatures of adaptive divergence?, (b) What is the functional space along which young sister species show divergence at the genomic level? and (c) How quickly might prezygotic and postzygotic reproductive barriers evolve? Analysis of 82 re-sequenced genomes of the Oriental Papilio polytes species group revealed surprisingly widespread hotspots of intense selection and selective sweeps at hundreds of genes, spanning all chromosomes, rather than divergence only in a few genomic islands. These genes are involved in diverse ecologically important adaptive functions such as wing development, colour patterning, courtship behaviour, mimicry, pheromone synthesis and olfaction, and host plant use and digestion of secondary metabolites, that could contribute to local adaptation and subsequent reproductive isolation. Divergence at such functional genes appeared to have evolved in conjunction with reproductive consequences: behavioural and hybridisation experiments revealed strong assortative mate preference (prezygotic barriers) as well as postzygotic barriers to hybridisation in timespans as short as 1.5 my, indicating that speciation was already complete rather than incipient. Our study thus demonstrates an underappreciated role of intense selection and potential local adaptation in creating genome-wide hotspots of rapid molecular evolution and divergence during differentiation and speciation in young allopatric species.

}, keywords = {assortative mating; postzygotic reproductive barriers; prezygotic reproductive barriers; selective sweeps; signatures of selection; speciation genomics.}, issn = {1365-294X}, doi = {10.1111/mec.17703}, url = {https://pubmed.ncbi.nlm.nih.gov/40035353/}, author = {Deshmukh, Riddhi and Baral, Saurav and Kuwalekar, Muktai and Kizhakke, Athulya Girish and Kunte, Krushnamegh} } @article {159724, title = {Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.}, journal = {PLoS Genet}, volume = {21}, year = {2025}, month = {2025 Aug}, pages = {e1011825}, abstract = {

In vertebrates, auditory information is transduced in the cochlea by mechanosensory hair cells (HC) through an eccentrically organised structure known as the hair bundle. This consists of a true cilium, known as the kinocilium, and modified microvilli, known as stereocilia. The hair bundle has a distinct structure with stereocilia organised in graded rows, with the longest abutting the kinocilium. The hair bundles of all HC are aligned to the tissue axis and are planar polarised. Important in the development and physiology of HC are protein bridges consisting of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). These link the tips of stereocilia, where they play a role in mechanotransduction, and between the kinocilia and the stereocilia, where they are involved in development. Both Cdh23 and Pcdh15 mutations result in defects in planar polarity; however, the mechanism through which this defect arises is unclear. Using a novel mutant for the Pcdh15-CD2 isoform, we show that while the initial deflection of the kinocilium occurs, its peripheral migration to register with Gαi is perturbed. Pcdh15-CD2 genetically interacts with Gpsm2, perturbing vestibular function. We find that the earliest expression of PCDH15-CD2 is at the base of the kinocilia, and the defects in morphogenesis occur before the formation of kinocilial links. By re-introducing functional PCDH15-CD2, we show that polarity can be restored. Our data suggest that, in addition to its adhesive role, PCDH15-CD2 has an early role in intrinsic hair cell polarity through a mechanism independent of kinocilial links.

}, keywords = {Animals, Basal Bodies, Cadherin Related Proteins, Cell Polarity, Ear, Inner, Gene Knock-In Techniques, Hair Cells, Auditory, Mice, Mutation, Phosphorylation, Protein Domains, Protein Precursors, Tyrosine}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1011825}, author = {Kaushik, Raman and Pandey, Shivangi and Prakash, Anubhav and Ganatra, Fenil and Abe, Takaya and Kiyonari, Hiroshi and Ladher, Raj K} } @article {154154, title = {Roof of the world: Home and border in the genomic era}, journal = {Molecular Ecology Resources}, year = {2025}, abstract = {

Himalaya and the Tibetan Plateau, known as the {\textquoteleft}land of snow{\textquoteright} and the {\textquoteleft}roof of the world{\textquoteright}, is home to tens of millions of indigenous people who live with a staggering amount of biological diversity. In the past decade scientists have applied genomic tools and methods to substantially advance the understanding of phylogeography and genetic mechanisms behind high-elevation adaptation of local biota. However, contributions from indigenous researchers and native institutions are underrepresented in this scientific endeavour. We point to the higher degree of indigenous contribution within the discipline of conservation biology and how recognizing the prominence of traditional ecological knowledge (TEK) could deliver keen molecular ecological insights. Since the Himalaya-Tibet ecological interface spans five countries, comprehensive biogeographical and phylogeographical taxon sampling in the region requires multi-national collaborations across indigenous lands as well as indigenous community participation at both national and international levels. For the next generation of indigenous molecular ecologists, researching and cataloguing the evolutionary history and genetic information of the Tibetan and Himalayan landscape is a race against the melting glacier. At the roof of the world, their scientific judgement and stewardship will have environmental impacts that percolate far beyond indigenous lands.

}, doi = { https://doi.org/10.1111/1755-0998.13827}, url = {https://onlinelibrary.wiley.com/doi/10.1111/1755-0998.13827}, author = {Wa Da and Suresh K. Rana and Kamal Bawa and Krushnamegh Kunte and Zhengyang Wang} } @article {157486, title = {Scientific Note: The first confirmed record of the genus Scoliokona Kallies \& Arita, 1998 (Lepidoptera: Sesiidae: Sesiinae) from India}, journal = {Tropical Lepidoptera Research}, volume = {35}, year = {2025}, month = {16 May 2025}, abstract = {

The clearwing moth species\ Scoliokona kalliesi\ Arita \& Riefenstahl, 2004 is recorded from the Jayanti region of Buxa Tiger Reserve, West Bengal, India. This is the first confirmed record of this genus and species from India, substantially extending the known range of the genus to the west.

}, url = {https://journals.flvc.org/troplep/article/view/139261}, author = {Sanjay Sondhi and Axel Kallies and Rachit Pratap Singh and Arjan Basu Roy and Krushnamegh Kunte} } @article {160530, title = {A Scientist Who Created Institutions With a Lasting Culture}, journal = {Resonance}, volume = {30}, year = {2025}, month = {18 August 2025}, pages = {1037{\textendash}1053}, type = {General Article}, abstract = {

Obaid Siddiqi (1932{\textendash}2013) was a pivotal figure in establishing modern molecular biology in India. His contributions started with fungal genetics, including the discovery of polarised {\textquoteleft}negative interference,{\textquoteright} then bacterial genetics, where he elucidated fundamental mechanisms of genetic suppression, DNA transfer, and conjugation. His research shift to Drosophila neurobiology was marked by collaborations with Seymour Benzer and Veronica Rodrigues, leading to insights into synaptic physiology and chemosensory pathways. Beyond his research, Siddiqi played a visionary role as an institution-builder, notably in founding the Molecular Biology Unit (MBU) at the Tata Institute of Fundamental Research (TIFR) and establishing the National Centre for Biological Sciences (NCBS) of TIFR. His mentorship philosophy, characterised by intellectual rigour, freedom, and personal care, cultivated generations of scientists. Siddiqi stands out as a figure whose approach to science and commitment to nurturing excellence had a national and global impact.

}, keywords = {behavioural genetics, chemosensory physiology, Drosophila, Genetic code, learning and memory, molecular biology}, doi = {https://doi.org/10.1007/s12045-025-1846-6}, url = {https://link.springer.com/article/10.1007/s12045-025-1846-6}, author = {K. VijayRaghavan} } @article {160478, title = {A Scientist Who Created Institutions With a Lasting Culture}, journal = {Reson }, volume = {30, 1037{\textendash}1053. }, year = {2025}, doi = {https://doi.org/10.1007/s12045-025-1846-6 }, author = {VijayRaghavan, K} } @article {161124, title = {Segregation, finite-time elastic singularities, and coarsening in renewable active matter}, journal = {Physical Review E}, volume = {112(4)}, year = {2025}, month = {24-10-2025}, type = {Journal}, abstract = {

Material renewability in active living systems, such as in cells and tissues, can drive the large-scale patterning of forces, with distinctive phenotypic consequences. This is especially significant in the cell cytoskeleton, where multiple species of myosin bound to actin, apply differential contractile stresses and undergo differential turnover, giving rise to patterned force channeling. Here we study the dynamical patterning of stresses that emerge in a hydrodynamic description of a renewable active actomyosin elastomer comprising two myosin species. Our analytical framework also holds for an actomyosin elastomer with a single myosin species. We find that a uniform active contractile elastomer spontaneously segregates into spinodal stress patterns, followed by a finite-time collapse into tension carrying singular structures that display self-similar scaling and caustics. Our numerical analysis carried out in one dimension shows that these singular structures move and merge and gradually result in a slow coarsening dynamics. We discuss the implications of our findings to the emergence of stress fibers and the spatial patterning of actomyosin. Our study suggests that with state-dependent turnover of crosslinkers and myosin, the\ in vivo\ cytoskeleton can navigate through the space of material parameters to achieve a variety of functional phenotypes.

}, author = {Ayan Roychowdhury{\textquoteright} and Saptarshi Dasgupta{\textquoteright} and Madan Rao} } @article {158506, title = {Sensing volatiles throughout the body: geographic- and tissue-specific olfactory receptor expression in the fig wasp}, year = {2025}, abstract = {

An essential adaptive strategy in insects is the evolution of olfactory receptors (ORs) to recognize important volatile environmental chemical cues. Our model species,\ Ceratosolen fusciceps, a specialist wasp pollinator of\ Ficus racemosa, likely possesses an OR repertoire that allows it to distinguish fig-specific volatiles in highly variable environments. Using a newly assembled genome-guided transcriptome, we annotated 63\ ORs\ in the species and reconstructed the phylogeny of\ Ceratosolen\ ORs in conjunction with other hymenopteran species. Expression analysis showed that though\ ORs\ were mainly expressed in the female antennae, 20\% were also expressed in nonantennal tissues such as the head, thorax, abdomen, legs, wings, and ovipositor. Specific upregulated expression was observed in\ OR30C\ in the head and\ OR60C\ in the wings. We identified\ OR\ expression from all major body parts of female\ C. fusciceps, suggesting novel roles of\ ORs\ throughout the body. Further examination of the\ OR\ expression of\ C. fusciceps\ in widely separated geographical locations, that is, South (urban) and Northeast (rural) India, revealed distinct\ OR\ expression levels in different locations. This discrepancy likely parallels the observed variation in fig volatiles between these regions and provides new insights into the evolution of insect\ ORs\ and their expression across geographical locations and tissues.

}, doi = {https://doi.org/10.1111/1744-7917.13441}, url = {https://onlinelibrary.wiley.com/doi/10.1111/1744-7917.13441}, author = {9. Krishnan S and Karpe SD and Kumar H and Nongbri LB and Venkateswaran V and Sowdhamini R and Grosse-Wilde E and Hansson BS and Borges RM} } @article {152150, title = {Sequence of the SARS-CoV-2 Spike Transmembrane Domain Encodes Conformational Dynamics.}, journal = {J Phys Chem B}, volume = {129}, year = {2025}, month = {2024 Dec 18}, pages = {194-209}, abstract = {

The homotrimeric SARS-CoV-2 spike protein enables viral infection by undergoing a large conformational transition, which facilitates the fusion of the viral envelope with the host cell membrane. The spike protein is anchored to the SARS-CoV-2 envelope by its transmembrane domain (TMD), composed of three TM helices, each contributed by one of the protomers of spike. Although the TMD is known to be important for viral fusion, whether it is a passive anchor of the spike or actively promotes fusion remains unknown. Specifically, it is unclear if the TMD and its dynamics facilitate the prefusion to postfusion conformational transition of the spike. Here, we computationally study the dynamics and self-assembly of the SARS-CoV-2 spike TMD in homogeneous POPC and cholesterol containing membranes. Atomistic simulations of a long TM helix-containing protomer segment show that the membrane-embedded segment bobs, tilts and gains and loses helicity, locally thinning the membrane. Coarse-grained multimerization simulations using representative TM helix structures from the atomistic simulations exhibit diverse trimer populations whose architecture depends on the structure of the TM helix protomer. While a symmetric conformation reflects the symmetry of the resting spike, an asymmetric TMD conformation could promote membrane fusion through the stabilization of a fusion intermediate. Together, our simulations demonstrate that the sequence and length of the SARS-CoV-2 spike TM segment make it inherently dynamic, that trimerization does not abrogate these dynamics and that the various observed TMD conformations may enable viral fusion.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.4c05270}, author = {Lall, Sahil and Balaram, Padmanabhan and Mathew, M K and Gosavi, Shachi} } @article {161123, title = {Setting up a baseline for long-term ecological monitoring of Kashmir Himalayan grasslands}, journal = {Grassland Science}, volume = {71(4); 204-218}, year = {2025}, month = {02-09-2025}, type = {Journal}, abstract = {

Grasslands play a crucial role in supporting biodiversity and providing essential ecosystem services for both wildlife and human wellbeing. Despite their ecological and economic importance, the glaring knowledge gaps in scientific understanding of the Himalayan grasslands hamper their effective scientific management and also impede global synthesis under growing environmental change. To address this gap, we established three long-term ecological monitoring grassland sites in the Kashmir Himalaya and developed a standardized monitoring protocol for these ecosystems. The data generated so far from these sites revealed significant variations in vegetation composition, structure, biomass dynamics and nutrient (carbon and nitrogen) levels. Analysis of plant functional groups (PFGs), such as grasses, forbs and legumes, indicates marked differences among and between the sites. Notably, Dachigam National Park, located at a lower elevation, exhibits higher aboveground biomass and carbon storage compared to the higher-elevation sites, indicating a greater capacity to buffer against environmental changes. Aboveground and belowground biomass showed a strong negative relationship, with higher elevation sites showing relatively more belowground biomass compared to the low elevation site. Among functional groups, grasses dominated the low elevation site, while forbs and legumes formed a major component of aboveground biomass in high elevation sites. Continued monitoring of these variables over time will be pivotal to understanding how these grasslands might respond to a changing climate. The implications of this baseline data for developing the targeted conservation and management strategies for the Himalayan grassland ecosystems, and also for better allowing global knowledge synthesis, are discussed.

}, doi = {https://doi.org/10.1111/grs.70012 }, author = {Ishrat Shaheen{\textquoteright} and Rayees .A Malik{\textquoteright} and Mahesh Sankaran{\textquoteright} and Manzoor A. Shah} } @article {162681, title = {Should elephants graze or browse? The nutritional and functional consequences of dietary variation in a mixed-feeding megaherbivore.}, journal = {R Soc Open Sci}, volume = {12}, year = {2025}, month = {2025 Nov}, pages = {250939}, abstract = {

Unlike specialist browsers and grazers, the diets of mixed-feeding megaherbivores are broad and complex, comprising numerous plant species of variable nutritional quality. Understanding key axes of nutritional variation in the diets of mixed-feeding megaherbivores is challenging but is crucial to understand their impacts on vegetation. Here, we revisit a long-standing debate on whether browse is more nutritious than grasses for elephants, as browse is thought to contain higher crude protein (CP). We quantified diet composition using carbon isotope analyses and analysed forage quality in 102 Asian elephant faecal samples from southern India, and found that high-browsing and low-browsing diets had similar forage quality, as indexed by nitrogen and carbon-to-nitrogen ratio. To explore the generality of this finding, we analysed nutritional differences between browse and grass across 141 plant species consumed by Asian elephants across their distribution range. We show that woody tissues and non-legume plants, which dominate elephant browse, do not have higher forage quality or CP than grasses, a trend which may be common in Asia{\textquoteright}s mixed-feeding large herbivores. Finally, based on the observed habitat-wide variation in browsing, we provide a new framework to assess the impacts of Asian elephants on woody vegetation, with important implications for carbon cycling.

}, issn = {2054-5703}, doi = {10.1098/rsos.250939}, author = {Gautam, Hansraj and Berzaghi, Fabio and Thanikodi, M and Ravichandran, Abhirami and Sreeman, Sheshshayee M and Sankaran, Mahesh} } @article {157496, title = {Social dominance in rats is a determinant of susceptibility to stress.}, journal = {Proc Natl Acad Sci U S A}, volume = {122}, year = {2025}, month = {2025 May 13}, pages = {e2412314122}, abstract = {

Establishing a dominance hierarchy in social organisms is important for access to resources. Stress has been proposed as a major factor influencing an animal{\textquoteright}s likely position in a social hierarchy. Although individual differences in vulnerability to stress are increasingly recognized, how social hierarchy affects vulnerability remains relatively understudied. Here, we examined how the social dominance status of adult male Sprague-Dawley rats influences their response to stress in interactions with a familiar animal living in the same cage, and separately when confronting an unfamiliar rat of uncertain dominance status from another cage, using the tube test. Having determined the relatively stable within-cage social dominance status of animals, half were subjected to a single episode of 2-h immobilization stress. Cagemates, both control and stressed rats, again faced one another 1 d and 10 d after stress. First, the predetermined hierarchical rank among familiar cagemates was relatively unaffected by stress. However, second, the same stress had a differential impact in competitions between unfamiliar rats. Socially dominant control rats continued to win competitions but subordinate control rats, that had previously lost, sometimes started to win against previously dominant rats that had been stressed. Strikingly, subordinate stressed rats displayed consistent submissive-like behavior and they alone showed differential effects on dendritic spine density in the amygdala. Thus, an individual{\textquoteright}s social rank can influence its response to stress, an effect that is detectable in interactions with unfamiliar animals. These findings provide an additional dimension to animal models of stress used for exploring facets of social anxiety and withdrawal in stress-related psychiatric disorders.

}, keywords = {dominance; stress; structural plasticity; susceptibility; tube test.}, issn = {1091-6490}, doi = {10.1073/pnas.2412314122}, url = {https://www.pnas.org/doi/10.1073/pnas.2412314122?url_ver=Z39.88-2003\&rfr_id=ori\%3Arid\%3Acrossref.org\&rfr_dat=cr_pub++0pubmed}, author = {Srinivasan, Durga J and Kapgal, Vijayakumar and Morris, Richard G M and Chattarji, Sumantra} } @article {162694, title = {Somatic hypermutation patterns are shaped by both motif position and sequence grammar.}, journal = {EMBO J}, year = {2025}, month = {2025 Dec 11}, abstract = {

Somatic hypermutation (SHM) in variable regions of immunoglobulin genes by activation-induced deaminase (AID) is essential for the maturation of protective antibodies against pathogen and vaccine antigens. AID preferentially mutates cytosines within WRCH motifs (wherein W = A/T, R = A/G, and H = A/C/T) in single-stranded DNA, yet these motifs show large but reproducible variation in mutation frequency, suggesting a crucial role for sequences flanking the WRCH motifs (i.e., a sequence grammar) in determining mutational outcomes. However, the nature of this sequence grammar is poorly understood. Here, we demonstrate that identical sequence contexts can exert significantly varying effects on the mutagenesis of different WRCH motifs. Molecular dynamics simulations reveal that both the sequence context and the specific WRCH motif modulate AID activity by altering the mode and strength of AID{\textquoteright}s interactions with single-stranded DNA. Repositioning a motif and its context within the variable region significantly alters its mutability. Therefore, the mutability of AID target cytosines is determined by a motif-specific sequence grammar that determines, in part, how activation-induced deaminase binds single-stranded DNA, as well as the motif position.

}, issn = {1460-2075}, doi = {10.1038/s44318-025-00640-9}, author = {Bartl, Bianca and Schoeberl, Ursula E and Valieris, Renan and Fitz, Johanna and Roeder, Konstantin and Vinothkumar, Kutti R and Gundinger, Benjamin and Tojal Da Silva, Israel and Pavri, Rushad} } @article {158503, title = {Spatial occurrence records and distributions of tropical Asian butterflies}, year = {2025}, abstract = {

Insect biogeography is poorly documented globally, particularly in the tropics. Recent intensive research in tropical Asia, combined with increasingly available records from citizen science, provides an opportunity to map the distributions of tropical Asian butterflies. We compiled a dataset of 730,190 occurrences of 3,752 tropical Asian butterfly species by aggregating records from GBIF (651,285 records), published literature (27,217), published databases (37,695), and unpublished data (13,993). Here, we present this dataset and single-species distribution maps of 1,576 species. Using these maps, along with records of the 2,176 remaining species, we identified areas of limited sampling (e.g., Myanmar and New Guinea) and predicted areas of high diversity (Peninsular Malaysia and Borneo). This dataset can be leveraged for a range of studies on Asian and tropical butterflies, including 1) species biogeography, 2) sampling prioritization to fill gaps, 3) biodiversity hotspot mapping, and 4) conservation evaluation and planning. We encourage the continued development of this dataset and the associated code as a tool for the conservation of tropical Asian insects.

}, doi = {10.1038/s41597-025-05333-w}, url = {https://www.nature.com/articles/s41597-025-05333-w}, author = {Eugene Yu Hin Yau and Emily E. Jones and Toby Pak Nok Tsang and Shuang Xing and Richard T. Corlett and Patrick Roehrdanz and David J. Lohman and Adam Kai Chi Lee and Catherine Wai Ching Hai and Shawan Chowdhury and Jane K. Hill and Jade A. T. Badon and Cheong Weei Gan and Yves Basset and I-Ching Chen and Suzan Benedick and Anuj Jain and Tiffany L. T. Ki and Krushnamegh Kunte and Akihiro Nakamura and Lien Van Vu and Sarah A. Scriven and Alice C. Hughes and Timothy C. Bonebrake} } @article {156925, title = {Species cover, community biomass, and richness in global grasslands from NutNet (2007{\textendash}2023): Dominant species predict plant richness and biomass in global grasslands}, year = {2025}, abstract = {
The Nutrient Network (NutNet) is a globally coordinated research initiative designed to investigate the impacts of human-driven alterations in nutrient availability and consumer presence on grassland ecosystems. Data were collected from over 130 herbaceous-dominated sites worldwide, spanning diverse environmental conditions from desert grasslands to arctic tundra. Standardized methodologies were employed across all sites to enable direct comparisons of productivity, diversity, and ecosystem responses. Experimental treatments included nutrient additions to assess co-limitation of plant growth by multiple nutrients, as well as grazer manipulations to examine their role in regulating biomass, species diversity, and community composition. By compiling these cross-site data, NutNet aims to enhance our understanding of productivity-diversity relationships and provide new insights into the ecological consequences of anthropogenic changes to nutrient cycles and food webs at a global scale.
}, url = {https://doi.org/10.6073/pasta/b9df4cb39a594b1bf0732085b69b74e5}, author = {Borer, Elizabeth and Seabloom, Eric and Slette, Ingrid and Wilfahrt, Peter and Asmus, Ashley and Sankaran, Mahesh} } @article {153340, title = {Structural analysis of genetic variants of the human tumor suppressor Palb2 coiled-coil domain.}, journal = {Biosci Rep}, year = {2025}, month = {2025 Jan 02}, abstract = {

The tumor suppressor PALB2 is a key player in the Homologous Recombination (HR) pathway, functionally connecting BRCA proteins at the DNA damage site. PALB2 forms homodimers via its coiled-coil domain, and during HR, it forms a heterodimeric complex with BRCA1 using the same domain. However, the structural details of the human PALB2 coiled-coil domain are unknown. Several missense variants have been reported in the coiled-coil domain. The structure-function relationship of these variants is poorly understood, posing a challenge to genetic counseling. In this study, we present the solution structure of the human PALB2 coiled-coil domain, which forms an antiparallel homodimer. We then use this structure to investigate the impact of a few well-characterized missense mutations on the fold and interactions of the PALB2 coiled-coil domain. Our findings reveal a strong correlation between the structural impact of mutations and their efficiency in homologous recombination, suggesting that our approach can be applied to study other genetic variations in PALB2. These findings hold promise for improving genetic counseling and advancing cancer research.

}, keywords = {DNA synthesis and repair; NMR spectroscopy; Tumor suppressor Palb2; breast cancer; missense mutations; molecular dynamics.}, issn = {1573-4935}, doi = {10.1042/BSR20241173}, url = {https://pubmed.ncbi.nlm.nih.gov/39745016/}, author = {Pothula Purushotham Reddy and Apurva Phale and Ranabir Das} } @article {157497, title = {Structure and dynamics of secondary and mature rainforests: insights from South Asian long-term monitoring plots}, journal = {Plant Ecology \& Diversity}, year = {2025}, month = {30 April 2025}, type = {Research Article}, abstract = {

Background

Tropical forests play a critical role in global biodiversity conservation and carbon storage. In human-modified landscapes, secondary forests are becoming increasingly common, yet their ecological functioning remains underexplored. Comparing the forest dynamics in mature and regenerating forests offers insights into forest recovery and carbon dynamics.

Aims

To compare forest structure, floristic composition, stand dynamics and carbon of a mature and secondary tropical rainforest.

Methods

We assessed tree community and carbon dynamics over 5 years in two 1-ha long-term ecosystem monitoring plots, one each in mature tropical rainforests (MR) and 10-year post-agroforestry secondary rainforests (SR) in India{\textquoteright}s Western Ghats mountains. Both plots were established in 2017 and monitored annually. We expected (1) higher tree diversity, differences in species composition, and greater carbon stock in MR; (2) higher carbon sequestration rates in SR; and (3) carbon dynamics shaped by growth and mortality in SR and MR, respectively.

Results

The SR plot had fewer species (67 vs. 84), stored substantially less carbon (76 vs. 193 Mg), and comprised a distinct community with fewer late-successional species than MR. SR gained 5.8 Mg carbon, due to tree growth exceeding losses from mortality, while in MR mortality exceeded growth and recruitment resulting in a 3.3 Mg carbon decline over five years.

Conclusion

While MR had higher tree diversity, carbon stocks and relatively intact composition, the high rates of biodiversity and carbon accrual in SR highlight the conservation and climate significance of post-agroforestry secondary forests. Moderate carbon losses noted here in MR, as in other mature South Asian tropical forests, is a cause for concern under ongoing climate change.

}, doi = {https://doi.org/10.1080/17550874.2025.2494204}, url = {https://www.tandfonline.com/doi/full/10.1080/17550874.2025.2494204?src=$\#$abstract}, author = {Akhil MuraliORCID Icon,ORCID Icon,ORCID Icon,ORCID Icon,ORCID Icon,ORCID Icon,ORCID Icon \& and Srinivasan Kasinathan and Kshama Bhat and Jayashree Ratnam and Mahesh Sankaran and Divya Mudappa and T. R. Shankar Raman and Anand M. Osuri} } @article {154147, title = {Structure of the Femoral Chordotonal Organ in the Oleander Hawkmoth, Daphnis nerii.}, journal = {The Journal of Comparative Neurology}, volume = {533}, year = {2025}, month = {2025 Feb}, pages = {e70022}, abstract = {

Insect legs serve as crucial organs for locomotion and also act as sensory probes into the environment. They are involved in several complex movements including walking, jumping, prey capture, manipulation of objects, and self-grooming. These behaviors require continuous modulation of motor output through mechanosensory feedback, which is provided by numerous mechanosensors located on the cuticle and within the soft tissue. A key mechanosensory organ in the insect leg, the femoral chordotonal organ (FeCO), detects movements of the femoro-tibial joint. This organ is multifunctional and senses both self-generated movements (proprioception) and external stimuli (exteroception). Movements of the tibia alter the length of FeCO, which activates the embedded mechanosensory neurons. Due to the mechanical nature of these stimuli, the structure and material properties of the FeCO are crucial for their function, alongside the encoding properties of FeCO neurons. Here, as a first step toward understanding how its structure modulates its function, we characterized the morphology and anatomy of FeCO in the hawkmoth Daphnis nerii. Using a combination of computed micro-tomography, neuronal dye fills, and confocal microscopy, we describe the structure of FeCO and the location, composition, and central projections of FeCO neurons. FeCO is located in the proximal half of the femur and is composed of the ventral (vFeCO) and dorsal scoloparia (dFeCO), which vary vastly in their sizes and in the number of neurons they house. Moreover, the characteristic accessory structures of chordotonal organs, the scolopales, significantly differ in their sizes when compared between the two scoloparia. FeCO neurons project to the central nervous system and terminate in the respective hemiganglia. Using these morphological data, we propose a mechanical model of FeCO, which can help us understand several FeCO properties relating to its physiological function.

}, keywords = {FeCO model; femoral chordotonal organs; femoro-tibial joint; mechanosensors; oleander hawkmoth Daphnis nerii; proprioception.}, issn = {1096-9861}, doi = {10.1002/cne.70022}, url = {https://pubmed.ncbi.nlm.nih.gov/39935029/}, author = {Virdi, Simran and Sane, Sanjay P} } @article {161980, title = {Structure-guided engineering of protein stability through core hydrophobicity.}, journal = {Protein Sci}, volume = {34}, year = {2025}, month = {2025 Dec}, pages = {e70360}, abstract = {

Engineering thermostable proteins is advantageous for industrial and biomedical applications, where improved thermal stability can enhance conformational integrity, prolong functional half-life, and increase catalytic efficiency at elevated temperatures. We explored modifying the length of buried hydrocarbon chains to improve protein thermal stability. By optimizing the hydrophobic core through targeted amino acid substitutions, we aimed to minimize internal voids and improve core packing. To achieve this, we developed an algorithm that replaces buried hydrophobic residues with longer or bulkier hydrophobic side chains. The algorithm calculates the free energy of unfolding (ΔG) for each substitution, selecting only significantly stabilizing configurations. Functionally important residues and contact networks were excluded from mutation to preserve protein function. We applied the method to several proteins from the beta-grasp fold family. For experimental validation, we chose NEDD8, a beta-grasp protein with poor solubility and low thermal stability. Two subtle substitutions predicted by our algorithm increased NEDD8{\textquoteright}s thermal stability by 1.7 kcal/mol and raised its melting point by 17{\textdegree}C. MD simulations and NMR spectroscopy revealed reduced conformational fluctuations and increased stabilizing interactions, such as hydrogen bonding and electrostatic contacts. Functional assays confirmed that the substitutions did not perturb NEDD8{\textquoteright}s global fold or interactions with cofactors and enzymes. These results highlight the effectiveness of tuning buried hydrophobic residues to enhance protein stability without compromising function. This strategy could serve as a general framework for designing robust therapeutic proteins and enzymes for industrial or biomedical applications.

}, keywords = {Algorithms, Amino Acid Substitution, Hydrophobic and Hydrophilic Interactions, Molecular Dynamics Simulation, NEDD8 Protein, Protein Conformation, Protein Engineering, Protein Stability, Thermodynamics}, issn = {1469-896X}, doi = {10.1002/pro.70360}, author = {Ravichandran, Aravind and Puri, Anindita and Bhate, Suhas H and Habibullah, Batul Ismail and Singh, Gajendra and Das, Ranabir} } @article {161983, title = {Synergism of IP3R and Parkin mutants identifies mitochondrial stress as an early feature of Parkinson{\textquoteright}s Disease.}, journal = {Dis Model Mech}, year = {2025}, month = {2025 Nov 14}, abstract = {

Our understanding of mechanisms underlying familial Parkinson{\textquoteright}s Disease (PD) have benefitted from studies in Drosophila models of PD. However, in a majority of PD patients the disease occurs sporadically and cellular phenotypes that arise early in sporadic PD remain to be understood. A genetic predisposition, arising from mutations in pathways that impact dopaminergic neuron health could be one cause of sporadic PD. Here, we studied Drosophila with single copies of recessive IP3R gene (itpr) mutants placed in combination with a recessive null mutant for the parkin gene. Whereas individual mutants appear normal, in combination they synergise to exhibit flight motor deficits with a focus in a subset of central dopaminergic neurons. Surprisingly, mitophagy and mitochondrial Ca2+ are barely affected. Instead, flight motor deficits correlate with elevated levels of mitochondrial H2O2 and reducing H2O2 levels by genetic means restored mitochondrial function and flight to a significant extent. This study underlines the importance of mitochondrial oxidative stress as an early phenotype in PD and suggests that humans with recessive mutations in either pathway have a higher chance of developing sporadic PD.

}, keywords = {Calcium homeostasis; Dopaminergic neurons; Flight; Motor function; PPL1}, issn = {1754-8411}, doi = {10.1242/dmm.052146}, author = {Dileep, Mrudula and Sharma, Anamika and Kasturacharya, Nandashree and Nizami, Syed Kavish and Manjila, Steffy and Bhan, Ashita and Hasan, Gaiti} } @article {156899, title = {Temperature switchable self-propulsion activity of liquid crystalline microdroplets.}, journal = {Soft Matter}, year = {2025}, month = {2025 Apr 17}, abstract = {

We report on a switchable emulsion droplet microswimmer by utilizing a temperature-dependent transition of the droplet phase. The droplets, made from a liquid crystalline (LC) smectic phase material ( = 25 {\textdegree}C), self-propel only in their nematic and isotropic phases at elevated temperatures ( >= 33.5 {\textdegree}C). This transition between motile and non-motile states is fully reversible - in the motile state, the droplets exhibit persistent motion and directional memory over multiple heating-cooling cycles. Furthermore, we distinguish the state of rest from the state of motion by characterizing the chemical and hydrodynamic fields of the droplets. Next, we map the motility behaviour of the droplets across varying surfactant concentrations and temperatures, observing that swimming occurs only at sufficiently high surfactant concentrations and temperatures above the smectic-nematic phase transition temperature >= 33.5 {\textdegree}C. Our work envisions the potential of LC emulsion droplets as temperature tunable microswimmers.

}, issn = {1744-6848}, doi = {10.1039/d4sm01382d}, url = {https://pubs.rsc.org/en/content/articlelanding/2025/sm/d4sm01382d}, author = {Kumar, Manoj and Sane, Siddharth and Murali, Aniruddh and Thutupalli, Shashi} } @article {161982, title = {Temperature-Driven Catalytic Switching Enables Sequence-Dependent Amplification of Autocatalytic Ribozymes in Coacervates.}, journal = {Small}, year = {2025}, month = {2025 Nov 18}, pages = {e07108}, abstract = {

Autocatalytic RNA networks confined within coacervate droplets represent minimal systems capable of self-reproduction and compositional variation. While such networks have been studied under static conditions, their behavior under fluctuating environments remains poorly understood. Here, the self-assembly dynamics of the Azoarcus ribozyme is investigated within spermine-polyacrylate coacervates subjected to thermal perturbations. It is shown that temperature acts as a switch for ribozyme catalysis: above a threshold, coacervates support autocatalytic RNA assembly; below it, reaction dynamics are arrested due to diffusion-limited transport. Notably, the switching kinetics are sequence-specific-different ribozyme variants exhibit distinct temperature thresholds for catalytic activity. Reaction rates deviate from Arrhenius behavior inside droplets, highlighting the nontrivial coupling between catalysis and compartmentalization. Finally, it is demonstrated that temperature cycling differentially amplifies ribozyme variants, with selective assembly emerging at intermediate cycling frequencies. These results reveal that fluctuating environments can bias reproduction dynamics in compartmentalized autocatalytic systems, providing a potential route for primitive functional differentiation and\ selection.

}, issn = {1613-6829}, doi = {10.1002/smll.202507108}, author = {Chakraborty, Nayan and Ameta, Sandeep and Thutupalli, Shashi} } @article {161977, title = {Three{\textquoteright}s Company: Human infrastructure and diminishing savannas accentuate meso-carnivore interactions in a shared landscape of western India.}, year = {2025}, abstract = {

Human changes to natural habitats affect carnivores differently{\textemdash}some species benefit from new resources, while others face higher risks. In semi-arid Kachchh, India, researchers studied four meso-carnivores (golden jackal, jungle cat, Indian fox, and desert cat). They mapped habitats, measured fragmentation, and used camera traps and signs to understand where each species occurs and how they interact. Despite being the most fragmented, open savanna still supported three of the four species. Larger species showed dominance patterns influencing how they share space and time. Human disturbances, especially roads, reduced how often species co-occurred. Protecting savanna habitats and considering species interactions in policy can help prevent competition-based losses and maintain healthy carnivore communities.

}, keywords = {Free-ranging dogsInterspecific interactionsHabitat useHuman impactsCarnivoresShared landscapesTropics}, doi = {https://doi.org/10.1016/j.biocon.2025.111618}, author = {Ganguly, D and Srivathsa, A and Vasudev, D and Ramakrishnan, U} } @article {156895, title = {Tiger turnaround as populations grow in India.}, journal = {Nature}, volume = {640}, year = {2025}, month = {2025 Apr}, pages = {603-604}, abstract = {

Until a few tens of thousands of years ago, Earth harboured a remarkable collection of large animals1, including giant ground sloths (Megatherium), woolly mammoths (Mammuthus primigenius) and elephant birds (Mullerornis\ and\ Aepyornis). Most of these iconic beasts are now extinct, and many large mammals are vanishingly rare following widespread human persecution and habitat disruption. Yet in India, a nation with a burgeoning human population, good news is reverberating about the population of wild tigers (Panthera tigris).\ Writing in\ Science, Jhala\ et al.2\ present findings about tigers that provide key lessons for conserving imperilled large animals elsewhere in the world.

}, issn = {1476-4687}, doi = {10.1038/d41586-025-01027-w}, url = {https://www.nature.com/articles/d41586-025-01027-w}, author = {Laurance, William F and Ramakrishnan, Uma} } @article {161981, title = {Timing of Delamination of Inner Ear Neurons Specifies Their Topography and Target Innervation.}, journal = {J Comp Neurol}, volume = {533}, year = {2025}, month = {2025 Nov}, pages = {e70103}, abstract = {

The neurons of the inner ear delaminate from a sensorineurogenic epithelium in the ventral part of the otocyst. Delaminated neuroblasts then condense to form the acoustico-vestibular ganglion (AVG). As they differentiate, the neurons connect mechanosensory hair cells (HCs) of the inner ear with their targets in the hindbrain in a precise topographical manner. However, it is unclear how or when positional identities of neurons are specified within the AVG, such that topographical information from HCs is maintained into the auditory centers of the brain. Here, we find that the time of delamination from the otocyst correlates with neuroblast position in the ganglion. Using markers for neuronal differentiation, we find that the ganglion differentiates from a dorsal to ventral wave. Neurons that differentiate first innervate the vestibular apparatus, including the lagena and the proximal regions of the BP. Using sequential somatic cell labeling, we find that the central projection also follows a similar dependency on delamination order. Our studies show that the time of delamination of otic neuroblasts presages their target innervation choice and fiber positions within the developing eighth cranial nerve. We suggest that temporal information specifies the spatial identities during early inner ear neuron development.

}, keywords = {Animals, Cell Differentiation, Chick Embryo, Ear, Inner, Neurogenesis, Neurons, Time Factors}, issn = {1096-9861}, doi = {10.1002/cne.70103}, author = {Saini, Surjit Singh and Ladher, Raj K} } @article {158960, title = {Towards Greener Pastures: An Overview of Pastoral Economics, Policies and Ecologies in India}, journal = {Economic \& Political Weekly}, year = {2025}, abstract = {

The ecological, economic, and policy challenges facing pastoralism and grassland ecosystems in India, particularly in the context of climate change and evolving land-use pressures are critically examined. Drawing upon a global literature, the paper contextualises Indian pastoralism and its grassland dynamics, highlighting the ecological factors shaping pastoralism across the country. It describes the pastoral economy, drawing attention to the often-underestimated size and scale of this enterprise. It then documents the historical mischaracterisation of rangelands as wastelands and argues that these ecosystems are vital for pastoral livelihoods and have unique biodiversity characteristics.

}, author = {Aniruddh, Sheth and Mayank, Kohli and Jayashree, Ratnam and Vasant, Saberwal and Mahesh, Sankaran} } @article {157484, title = {Trace DNA from kill sites identifies individual predators}, journal = {Biological Conservation}, volume = {307}, year = {2025}, month = {July 2025}, pages = {111117}, type = {Research Article}, abstract = {

Predation ecology and evidence-based conflict management strategies require reliable and accurate identification of individual predators. Identifying predators is, however, complex, as they are secretive and individual identification is difficult. Trace DNA that predators leave behind at kill sites might provide an effective strategy to identify them but remains poorly assessed. We use non-invasive genetic samples from kill sites to assess their utility for predator identification. We systematically investigated 198 livestock kills in two of Central India{\textquoteright}s critical source tiger populations: Kanha and Bandhavgarh Tiger Reserves. We collected 342 saliva, 33 scat and 395 shed hair samples as potential sources of predator DNA. Individual tigers were identified using up to 123 SNP markers. All sample types were highly successful (\>95\ \%) in identifying tigers. Individual tigers were identified at 85\ \% of all kill sites using at least one sample. Shed hair samples were most effective for individual identification, followed by saliva and scat. Sample type and sampling season were the primary determinants of the number of SNPs typed per sample and individual identification success. Based on the collection site and type of sample in identification, we classified species and individuals into three categories: true predator (high confidence as predator), circumstantial predator (medium confidence) and predator uncertain (low confidence). Individuals were classified as a true predator at 72 sites, circumstantial predator at 34 sites, and predator uncertain at 49 sites. We suggest that when paired with systematic kill site investigation and sample collection, these methods can be effectively used to understand predation ecology better and facilitate evidence-based conflict management.

}, doi = {https://doi.org/10.1016/j.biocon.2025.111117}, url = {https://www.sciencedirect.com/science/article/pii/S0006320725001545?dgcid=author}, author = {Himanshu Chhattani and Abishek Harihar and Rounak Dean and Ajay Yadav and Kaushal Patel and Divyashree Rana and Awadhesh Pandit and Sanjay Kumar Shukla and Vincent Rahim and Uma Ramakrishnan} } @article {156893, title = {Transcriptional and epigenomic changes in response to PEG-triggered osmotic stress in rapeseed (Brassica napus L.).}, journal = {J Exp Bot}, year = {2025}, month = {2025 Apr 03}, abstract = {

Drought hinders growth, development, and productivity of higher plants. While physiological and molecular background of plant responses to drought has been extensively studied, the role of post-translational modifications of histones or DNA methylation in response to dehydration remains largely elusive. In this study, we deciphered genome-wide changes in transcriptome and histones modifications in response to dehydration in rapeseed (Brassica napus L.). High-throughput transcript profiling (RNA-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) of PEG-treated rapeseed plants revealed genome-scale changes in transcription and histone methylation patterns, specifically in histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 tri-methylated lysine 27 (H3K27me3) sites. We have identified gene sets with altered transcript profiles as well as histone methylation marks in response to osmotic stress. Several proline biosynthesis regulatory genes coding for Delta 1-Pyrroline-5-Carboxylate Synthetases (P5CS) displayed changes in H3K4me3 and/or H3K36me3 enrichment post PEG treatment. Targeted bisulphite sequencing further identified stress-dependent gene body DNA methylation in one of the BnP5CSA gene copies that correlates with its stress-induced activation. By integrating physiological, transcriptional and epigenomic data, our study contributes to a better understanding of the drought response control in crop plants.

}, keywords = {ChIP; DNA methylation; Drought responsive genes; H3K27me3; H3K4me3; Histone methylation; P5CS genes; Proline; Rapeseed; Transcriptome.}, issn = {1460-2431}, doi = {10.1093/jxb/eraf123}, url = {https://pubmed.ncbi.nlm.nih.gov/40178034/}, author = {Prasad, Melvin and Shetty, Prateek and Pal, Avik Kumar and Rig{\'o}, G{\'a}bor and Kant, Kamal and Zsigmond, Laura and Nagy, Istv{\'a}n and Shivaprasad, P V and Szabados, L{\'a}szl{\'o}} } @article {154156, title = {Two new species of Merogomphus Martin, 1904 (Odonata: Anisoptera: Gomphidae) from the Western Ghats, India}, journal = {Zootaxa}, volume = {5588}, year = {2025}, month = {14 February 2025}, pages = {201-226}, type = {Research Article}, chapter = {201}, abstract = {

We describe two new species of dragonflies from the Western Ghats Biodiversity Hotspot,\ Merogomphus aryanadensis\ sp. nov.\ from Kerala and\ M. flavoreductus\ sp. nov.\ from Maharashtra, India. Morphologically, these species are closely aligned with\ M. tamaracherriensis\ Fraser, 1931, an endemic species of the Western Ghats; however, they are distinguished by unique features in their caudal appendages, accessory genitalia, and body markings. Additionally, both species are considerably smaller than other known\ Merogomphus\ spp. found in India. The differential diagnosis presented includes a comprehensive morphological photographic assessment of the two new species described and their two endemic congeners, also from the Western Ghats. We also establish a significant genetic distance between these newly described\ Merogomphus\ species and\ M. tamaracherriensis.

}, doi = {10.11646/zootaxa.5588.2.1}, url = {https://www.mapress.com/zt/article/view/zootaxa.5588.2.1}, author = {AYIKKARA VIVEK CHANDRAN and DATTAPRASAD SAWANT and REJI CHANDRAN and PANKAJ KOPARDE and SUBIN KANIYAMATTATHIL JOSE and Krushnamegh Kunte} } @article {158496, title = {Uncovering the transcription factors and metabolic pathways unique to proso millet and foxtail millet under salt stress through a comparative transcriptome approach}, year = {2025}, abstract = {

Salt stress causes major losses to crop production all over the globe. Millets being the climate-resilient crop possess the potential to overcome adverse abiotic stress conditions including salinity in comparison with other crops. Molecular level understanding of gene expressions that confer resistance to salt stress will increase food production as well as security. In addition to climatic resilient properties, they provide a high level of protein as well as important minerals like magnesium, phosphorus, and iron. In this study, we have compared the salt resistance responsible genes between proso millet and foxtail millet. The findings of this study compare the responses of foxtail and proso millets to salt stress and reveal a common metabolic network with 137 metabolic pathways that support salt tolerance. Pathways such as amino sugar and nucleotide sugar metabolism, phenylpropanoid biosynthesis, and different fundamental metabolism and energy-generating routes are examples of shared metabolic pathways. Salt stress signal conversion and energy metabolism under stress are both explained by the shared "Calcium signaling pathway" and "Oxidative phosphorylation pathway", respectively. Both species have distinctive metabolic pathways, which may indicate that they have each evolved differently in response to environmental forces. Notably, the species-specific transcription factors such as\ HD-ZIP\ and\ NAC\ in foxtail millet, and bHLH, ERF, and MYB-related in proso millet, highlight unique regulatory networks tailored to their environmental adaptations. The study also identified important transcription factors, including\ WRKY,\ bHLH,\ GRAS,\ Dof, and\ C3H, emphasizing their potential roles in increasing salinity tolerance and modifying stress responses. The enzymatic landscape includes both typical and unusual enzymes that take part in various pathways and are essential for metabolic adaptation.

}, keywords = {Proso millet {\textperiodcentered} Foxtail millet {\textperiodcentered} Metabolic pathways {\textperiodcentered} Transcription factor {\textperiodcentered} And abiotic stress}, doi = {10.1007/s44372-025-00237-w}, url = {https://link.springer.com/article/10.1007/s44372-025-00237-w}, author = {Anitha Ravichandran and Saranya Nallusamy and Selva Babu Selvamani and Ramanathan Sowdhamini} } @article {161127, title = {Understanding the roles of secondary shell hotspots in protein-protein complexes}, journal = {Proteins: Structure, Function, and Bioinformatics}, year = {2025}, month = {2025 Oct 4}, type = {Research Article}, abstract = {

Hotspots are interfacial residues in protein-protein complexes that contribute significantly to complex stability. Methods for identifying interfacial residues in protein-protein complexes are based on two approaches, namely, (a) distance-based methods, which identify residues that form direct interactions with the partner protein and (b) Accessibility Surface Area (ASA)-based methods, which identify those residues which are solvent-exposed in the isolated form of the protein and become buried upon complex formation. In this study, we introduce the concept of secondary shell hotspots, which are hotspots uniquely identified by the distance-based approach, staying buried in both the bound and isolated forms of the protein and yet forming direct interactions with the partner protein. From the analysis of the dataset curated from Docking Benchmark 5.5, comprising of 94 protein-protein complexes, we find that secondary shell hotspots are more evolutionarily conserved and have distinct Chou-Fasman propensities and interaction patterns compared to other hotspots. Finally, we present detailed case studies to show that the interaction network formed by the secondary shell hotspots is crucial for complex stability and activity. Further, they act as potentially allosteric propagators and bridge interfacial and non-interfacial sites in the protein. Their mutations to any other amino acid types cause significant destabilization. Overall, this study sheds light on the uniqueness and importance of secondary shell hotspots in protein-protein complexes.

}, keywords = {Accessible Surface Area (ASA), hotspot residues, Interface residues, Perturbation Response Scanning (PRS, Protein Sidechain Network (PScN), protein-protein interactions, residue conservation}, issn = {0887-3585}, doi = {DOI: https://doi.org/10.1002/prot.70074 }, author = {Parvathy, J{\textquoteright} and Yazhini, A{\textquoteright} and Srinivasan, N{\textquoteright} and Sowdhamini, R{\textquoteright}} } @article {159721, title = {upstream deletion leads to dysregulation of and autosomal gene expression.}, journal = {Genome Res}, year = {2025}, month = {2025 Aug 06}, abstract = {

long noncoding RNA is the master regulator of the X-Chromosome inactivation (XCI) process. is expressed from the inactive X and coats the inactive X to facilitate XCI. -regulation of expression remains poorly understood in the context of maintenance of XCI. Here, we have explored the role of the upstream sequences (\~{}6 kb) lying between and in the regulation of and XCI in mouse extra-embryonic endoderm stem cells (XEN), which represent the maintenance phase of imprinted XCI. Here, we show that the deletion of this upstream sequence in the inactive X leads to the upregulation of expression accompanied by the dispersal of the cloud. Notably, we find the loss of enrichment of repressive marks such as H3K27me3, H4K20me1, and MacroH2A, except that of H2AK119ub, in dispersed nuclei. However, X-linked genes remain silent despite dispersal and loss of enrichment of repressive marks. Notably, we find that many autosomal genes, including cohesin , are dysregulated in -upstream-deleted cells. Additionally, we demonstrate that -upstream deletion leads to alterations of topological contacts of the locus with its upstream positive regulator and across the inactive X and autosomes. Finally, we show genome-wide alterations of the occupancy of architectural proteins CTCF/RAD21, including at many loci of the inactive X such as the upstream regions and the locus, which is critical for maintaining inactive X conformation. Taken together, we demonstrate that the upstream sequence imparts a multifaceted role in genome regulation beyond the XCI.

}, issn = {1549-5469}, doi = {10.1101/gr.279822.124}, author = {Majumdar, Sudeshna and Bammidi, Lakshmi Sowjanya and Naik, Hemant C and Manhas, Avinchal and Baro, Runumi and Kalita, Akash and Naskar, Amlan Jyoti and Nidharshan, Sundarraj and Bariha, Girija S and Notani, Dimple and Gayen, Srimonta} } @article {159715, title = {Using protein blocks to build custom fragment libraries from protein structures.}, journal = {Biochimie}, year = {2025}, month = {2025 Aug 13}, abstract = {

The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous proteins but also in the recurrence of supersecondary motifs across unrelated proteins, underscoring the abundance and robustness of these structural units. Here, we present a novel pipeline for generating customized protein fragment libraries using protein blocks (PBs)-a structural alphabet that encodes local backbone conformations. Our method efficiently extracts structurally similar fragments from a curated, non-redundant protein structure database by converting three-dimensional structures into one-dimensional PB sequences. By integrating predicted PB sequences with the PB-ALIGN and PB-kPRED tools, our approach identifies relevant fragments independently of sequence homology. Fragment quality is further assessed using a new scoring function that combines secondary structure similarity and PB alignment metrics. The resulting libraries contain fragments of at least seven PBs (11 amino acid residues), covering over 70 \% of the local backbone structure. Our results demonstrate that PBs enable efficient mining of high-quality structural fragments from diverse protein spaces, including proteins with disordered regions. The pipeline is accessible as an online tool (PB-Frag, http://pbpred-us2b.univ-nantes.fr/pbfrag).

}, issn = {1638-6183}, doi = {10.1016/j.biochi.2025.08.011}, author = {Dhingra, Surbhi and T{\'e}letch{\'e}a, St{\'e}phane and Sowdhamini, Ramanathan and Sanejouand, Yves-Henri and de Brevern, Alexandre G and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard} } @article {150019, title = {Acute Activation of Genes Through Transcriptional Condensates Impact Non-target Genes in a Chromatin Domain}, journal = {eLife}, year = {2024}, month = {11/2024}, abstract = {

Transcription activation of genes by estrogens is driven by enhancers, which are often located within the same Topologically Associating Domain (TAD) as non-targeted promoters. We investigated how acute enhancer-driven activation affects neighbouring non-target genes within the same TAD. Using single-molecule RNA FISH (smFISH), we tracked the transcription of TFF1 (enhancer-targeted) and TFF3 (non-targeted) during estrogen stimulation. We observed mutually exclusive expression patterns: TFF1 expression peaked at 1 hour, while TFF3 reached its peak at 3 hours, after TFF1{\textquoteright}s activation had diminished. Chromatin looping data indicated that the enhancer loops with TFF1 but not TFF3, suggesting that TFF3 upregulation is not due to direct enhancer-promoter interactions. CRISPR deletion of the TFF1 enhancer and 1,6-hexanediol (HD) exposure revealed that the TFF1 enhancer:promoter undergo Liquid-Liquid Phase Separation (LLPS), which sequesters the transcriptional machinery and inhibits TFF3 expression. As estrogen signalling wanes or LLPS is disrupted, TFF1 expression declines while TFF3 expression increases. Our findings reveal that enhancer-driven activation can indirectly influence neighbouring genes, highlighting a dynamic shift in gene expression as signalling progresses.

}, doi = {10.7554/eLife.102417.1}, author = {Bohra, Darshika and Islam, Zubairul and Nidharshan, Sundarraj and Mazumder, Aprotim and Notani, Dimple} } @article {144783, title = {Albumin Oxidation and Albumin Glycation Discordance During Type 2 Diabetes Therapy: Biological and Clinical Implications.}, journal = {Metab Syndr Relat Disord}, volume = {22}, year = {2024}, month = {2024 Jun}, pages = {372-384}, abstract = {

Cys34 albumin redox modifications (reversible "cysteinylation" and irreversible "di/trioxidation"), besides being just oxidative stress biomarkers, may have primary pathogenetic roles to initiate and/or aggravate cell, tissue, and vascular damage in diabetes. In an exploratory "proof-of-concept" pilot study, we examined longitudinal changes in albumin oxidation during diabetes therapy. Mass spectrometric analysis was utilized to monitor changes in human serum albumin (HSA) post-translational modifications {glycation [glycated albumin (GA)], cysteinylation [cysteinylated albumin (CA) or human non-mercaptalbumin-1; reversible], di/trioxidation (di/trioxidized albumin or human non-mercaptalbumin-2; irreversible), and truncation (truncated albumin)} during ongoing therapy. Four informative groups of subjects were evaluated [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity, and healthy controls] at baseline, and subjects with diabetes were followed for a period up to 280 days. At baseline, T2DM was associated with relatively enhanced albumin cysteinylation (CA\% total) compared with T1DM ( = 0.004), despite comparable mean hyperglycemia ( values: hemoglobin A1c = 0.09; GA = 0.09). T2DM, compared with T1DM, exhibited selectively and significantly higher elevations of all the "individual" glycated cum cysteinylated ("multimodified") albumin isoforms ( values: CysHSA+1G = 0.003; CysHSA+2G = 0.007; and CysHSA+3G = 0.001). Improvements in glycemic control and decreases in albumin glycation during diabetes therapy in T2DM were not always associated with concurrent reductions of albumin cysteinylation, and in some therapeutic situations, albumin cysteinylation worsened (glycation-cysteinylation discordance). Important differences were observed between the effects of sulfonylureas and metformin on albumin molecular modifications. T2DM was associated with higher oxidative (cysteinylation) and combined (cysteinylation plus glycation) albumin molecular modifications, which are not ameliorated by improved glucose control alone. Further studies are required to establish the clinical significance and optimal therapeutic strategies to address oxidative protein damage and resulting consequences in diabetes.

}, keywords = {Adult, Aged, Biomarkers, Blood Glucose, Case-Control Studies, Cysteine, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Glycated Serum Albumin, Glycation End Products, Advanced, Glycosylation, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Oxidation-Reduction, Oxidative Stress, Pilot Projects, Protein Processing, Post-Translational, Serum Albumin, Serum Albumin, Human}, issn = {1557-8518}, doi = {10.1089/met.2023.0275}, author = {Vaishnav, Madhumati S and Kumari, Namita and Srikanta, Sathyanarayana and Simha, Vinaya and Krishnaswamy, Patnam R and Balaram, Padmanabhan and Bhat, Navakanta} } @article {150947, title = {AlphaFold opens the doors to deorphanizing secreted proteins.}, journal = {Cell Syst}, volume = {15}, year = {2024}, month = {2024 Nov 20}, pages = {1000-1001}, abstract = {

Danneskiold-Sams{\o}e and coworkers have developed an in silico screening pipeline based on AlphaFold2 for identifying single-pass transmembrane receptors for secreted peptides that play important roles in cell-cell signaling. Their approach can be used to deorphanize a diverse range of ligands. The overall strategy can be valuable in screening for weak and transient interactions.

}, keywords = {Computer Simulation, Humans, Ligands, Proteins, Signal Transduction}, issn = {2405-4720}, doi = {10.1016/j.cels.2024.10.010}, author = {Viswanath, Shruthi} } @article {149374, title = {Anatomical traits explain drought response of seedlings from wet tropical forests.}, journal = {Ecol Evol}, volume = {14}, year = {2024}, month = {2024 Sep}, pages = {e70155}, abstract = {

Water availability regulates plant community dynamics but the drought response of seedlings remains poorly known, despite their vulnerability, especially for the Asian tropics. In particular, discerning how functional traits of seedlings mediate drought response can aid generalizable predictions of tree responses to global environmental change. We assessed interspecific variation in drought response explained by above- and below-ground seedling traits. We conducted a dry-down experiment in the greenhouse using 16 tree species from the humid forests of Western Ghats in southern India, chosen to represent differences in affinity to conditions of high and low seasonal drought (seasonality affiliation). We compared survival, growth, and photosynthetic performance under drought and well-watered conditions and assessed the extent to which species{\textquoteright} responses were explained by seasonality affiliation and 12 traits of root, stem and leaf. We found that the species from seasonally dry forest reduced photosynthetic rate in drought compared with well-watered conditions, but seasonality affiliation did not explain differences in growth and survival. Performance in drought vs well-watered conditions were best explained by anatomical traits of xylem, veins and stomata. Species with larger xylem reduced their growth and photosynthesis to tolerate desiccation. In drought, species with smaller stomata correlated with lower survival even though photosynthetic activity decreased by a larger extent with larger stomata. Overall, anatomical traits of xylem and stomata, directly related to water transport and gas-exchange, played a more prominent role than commonly used traits (e.g., specific leaf area, leaf dry matter content) in explaining species response to drought, and may offer a good proxy for physiological traits related to drought tolerance of seedlings.

}, issn = {2045-7758}, doi = {10.1002/ece3.70155}, author = {Jhaveri, Rishiddh and Cannanbilla, Lakshmipriya and Bhat, K S Arpitha and Sankaran, Mahesh and Krishnadas, Meghna} } @article {147284, title = {Ascertaining the spatiotemporal variations in seaweed assemblages associated with the endemic seaweed Ulva ovata along selected locations of the Gulf of Khambhat, India}, journal = {AQUATIC ECOLOGY}, year = {2024}, month = {07/2024}, abstract = {

This investigation presents pioneering discoveries concerning the endemic seaweed Ulva ovata across multiple sites in the Gulf of Khambhat, India, going beyond its type locality, Gopnath. The primary objective of this research was to examine the substrate type and various environmental factors affecting seaweed diversity at five sites where endemic U. ovata was found. Identifying 11 seaweed species under Chlorophyta and Rhodophyta phyla, the study highlights rocky sites exhibiting higher Simpson (D) and Shannon (H {\textquoteright}) diversity indices, species richness, and percentage cover during cold months. k-dominance analysis indicates more species at Pingaleshwar, Unchakotda, and Gopnath. Bray Curtis similarity shows similarity in seaweed composition between Unchakotda-Pingaleshwar, and Kuda-Khadsaliya, whereas Gopnath forms a different cluster mode. Key species U. rigida and U. ovata, identified by SIMPER analysis, act as bio-indicators for future studies. Five sites demonstrate distinct seawater temperature, dissolved oxygen, light intensity, salinity, total dissolved solids (TDS), electrical conductivity (EC), wind velocity, UV index, nitrate (NO3-), and nitrite (NO2-) significantly impacting seaweed diversity. This study enhances understanding of seaweed distribution and environmental influences in the Gulf of Khambhat, offering insights into ecological dynamics and implications for marine conservation and management strategies.

}, doi = {10.1007/s10452-024-10127-0}, author = {Rathod, Sachin G. and Singh, Anshika and Mantri, Vaibhav A.} } @article {152898, title = {BharatSim: An agent-based modelling framework for India.}, journal = {PLoS Comput Biol}, volume = {20}, year = {2024}, month = {2024 Dec}, pages = {e1012682}, abstract = {

BharatSim is an open-source agent-based modelling framework for the Indian population. It can simulate populations at multiple scales, from small communities to states. BharatSim uses a synthetic population created by applying statistical methods and machine learning algorithms to survey data from multiple sources, including the Census of India, the India Human Development Survey, the National Sample Survey, and the Gridded Population of the World. This synthetic population defines individual agents with multiple attributes, among them age, gender, home and work locations, pre-existing health conditions, and socio-economic and employment status. BharatSim{\textquoteright}s domain-specific language provides a framework for the simulation of diverse models. Its computational core, coded in Scala, supports simulations of a large number of individual agents, up to 50 million. Here, we describe the design and implementation of BharatSim, using it to address three questions motivated by the COVID-19 pandemic in India: (i) When can schools be safely reopened given specified levels of hybrid immunity?, (ii) How do new variants alter disease dynamics in the background of prior infections and vaccinations? and (iii) How can the effects of varied non-pharmaceutical interventions (NPIs) be quantified for a model Indian city? Through its India-specific synthetic population, BharatSim allows disease modellers to address questions unique to this country. It should also find use in the computational social sciences, potentially providing new insights into emergent patterns in social behaviour.

}, keywords = {Algorithms, Computational Biology, Computer Simulation, COVID-19, Humans, India, Machine Learning, Pandemics, SARS-CoV-2, Systems Analysis}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1012682}, author = {Cherian, Philip and Kshirsagar, Jayanta and Neekhra, Bhavesh and Deshkar, Gaurav and Hayatnagarkar, Harshal and Kapoor, Kshitij and Kaski, Chandrakant and Kathar, Ganesh and Khandekar, Swapnil and Mookherjee, Saurabh and Ninawe, Praveen and Noronha, Riz Fernando and Ranka, Pranjal and Sinha, Vaibhhav and Vinod, Tina and Yadav, Chhaya and Gupta, Debayan and Menon, Gautam I} } @article {149383, title = {CDS2 expression regulates de novo phosphatidic acid synthesis.}, journal = {Biochem J}, volume = {481}, year = {2024}, month = {2024 Oct 16}, pages = {1449-1473}, abstract = {

CDS enzymes (CDS1 and 2 in mammals) convert phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of PI. Genetic deletion of CDS2 in primary mouse macrophages resulted in only modest changes in the steady-state levels of major phospholipid species, including PI, but substantial increases in several species of PA, CDP-DG, DG and TG. Stable isotope labelling experiments employing both 13C6- and 13C6D7-glucose revealed loss of CDS2 resulted in a minimal reduction in the rate of de novo PI synthesis but a substantial increase in the rate of de novo PA synthesis from G3P, derived from DHAP via glycolysis. This increased synthesis of PA provides a potential explanation for normal basal PI synthesis in the face of reduced CDS capacity (via increased provision of substrate to CDS1) and increased synthesis of DG and TG (via increased provision of substrate to LIPINs). However, under conditions of sustained GPCR-stimulation of PLC, CDS2-deficient macrophages were unable to maintain enhanced rates of PI synthesis via the {\textquoteright}PI cycle{\textquoteright}, leading to a substantial loss of PI. CDS2-deficient macrophages also exhibited significant defects in calcium homeostasis which were unrelated to the activation of PLC and thus probably an indirect effect of increased basal PA. These experiments reveal that an important homeostatic response in mammalian cells to a reduction in CDS capacity is increased de novo synthesis of PA, likely related to maintaining normal levels of PI, and provides a new interpretation of previous work describing pleiotropic effects of CDS2 deletion on lipid metabolism/signalling.

}, keywords = {Animals, Calcium, Diacylglycerol Cholinephosphotransferase, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphatidic Acids}, issn = {1470-8728}, doi = {10.1042/BCJ20240456}, author = {Collins, Daniel M and Janardan, Vishnu and Barneda, David and Anderson, Karen E and Niewczas, Izabella and Taylor, Diane and Qiu, Danye and Jessen, Henning J and Lopez-Clavijo, Andrea F and Walker, Simon and Raghu, Padinjat and Clark, Jonathan and Stephens, Len R and Hawkins, Phillip T} } @article {150944, title = {Cell shape affects bacterial colony growth under physical confinement.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Nov 08}, pages = {9561}, abstract = {

Evidence from homogeneous liquid or flat-plate cultures indicates that biochemical cues are the primary modes of bacterial interaction with their microenvironment. However, these systems fail to capture the effect of physical confinement on bacteria in their natural habitats. Bacterial niches like the pores of soil, mucus, and infected tissues are disordered microenvironments with material properties defined by their internal pore sizes and shear moduli. Here, we use three-dimensional matrices that match the viscoelastic properties of gut mucus to test how altering the physical properties of their microenvironment influences the growth of bacteria under confinement. We find that low aspect\ ratio (spherical) bacteria form compact, spherical colonies under confinement while high aspect\ ratio (rod-shaped) bacteria push their progenies further outwards to create elongated colonies with a higher surface area, enabling increased access to nutrients. As a result, the population growth of high aspect\ ratio bacteria is, under the tested conditions, more robust to increased physical confinement compared to that of low aspect\ ratio bacteria. Thus, our experimental evidence supports that environmental physical constraints can play a selective role in bacterial growth based on cell shape.

}, keywords = {Bacteria, Cell Shape, Escherichia coli}, issn = {2041-1723}, doi = {10.1038/s41467-024-53989-6}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Sanjenbam, Pratibha and Kurzthaler, Christina and Agashe, Deepa and Bhattacharjee, Tapomoy} } @article {140649, title = {Challenges and opportunities for discovering the biology of rare genetic diseases of the brain.}, journal = {J Biosci}, volume = {49}, year = {2024}, month = {2024}, abstract = {

Diseases of the human nervous system are an important cause of morbidity and mortality worldwide. These disorders arise out of multiple aetiologies of which rare genetic mutations in genes vital to nervous system development and function are an important cause. The diagnosis of such rare disorders is challenging due to the close overlap of clinical presentations with other diseases that are not of genetic origin. Further, understanding the mechanisms by which mutations lead to altered brain structure and function is also challenging, given that the brain is not readily accessible for tissue biopsy. However, recent developments in modern technologies have opened up new opportunities for the analysis of rare genetic disorders of the brain. In this review, we discuss these developments and strategies by which they can be applied effectively for better understanding of rare diseases of the brain. This will lead to the development of new clinical strategies to manage brain disorders.

}, keywords = {Biology, Brain, Humans, Mutation, Rare Diseases}, issn = {0973-7138}, author = {Raghu, Padinjat and Sharma, Yojet and Suseela Devi, Aswathy Bhuvanendran Nair and Krishnan, Harini} } @article {142319, title = {Chromosome organization shapes replisome dynamics in Caulobacter crescentus.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Apr 24}, pages = {3460}, abstract = {

DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial species, driving the hypothesis that a physical linker may tether them together. However, replisome splitting has also been reported in many of the same species, leaving the principles behind replisome organization a long-standing puzzle. Here, by tracking the replisome β-clamp subunit in live Caulobacter crescentus, we find that rapid DNA segregation can give rise to a second focus which resembles a replisome, but does not replicate DNA. Sister replisomes can remain colocalized, or split apart to travel along DNA separately upon disruption of chromosome inter-arm alignment. Furthermore, chromosome arm-specific replication-transcription conflicts differentially modify replication speed on the two arms, facilitate the decoupling of the two replisomes. With these observations, we conclude that the dynamic chromosome organization flexibly shapes the organization of sister replisomes, and we outline principles which can help to reconcile previously conflicting models of replisome architecture.

}, keywords = {Bacterial Proteins, Caulobacter crescentus, Chromosome Segregation, Chromosomes, Bacterial, DNA Replication, DNA, Bacterial}, issn = {2041-1723}, doi = {10.1038/s41467-024-47849-6}, author = {Zhang, Chen and Joseph, Asha Mary and Casini, Laurent and Collier, Justine and Badrinarayanan, Anjana and Manley, Suliana} } @article {152246, title = {Climate and vegetation collectively drive soil respiration in montane forest-grassland landscapes of the southern Western Ghats, India}, journal = {Journal of Tropical Ecology}, volume = {40}, year = {2024}, month = {09/2024}, chapter = {e16}, abstract = {

CO2 release rates from soils via soil respiration play an important role in the carbon budget of terrestrial ecosystems. Though the roles of soil temperature and moisture on soil respiration are well recognised, less is known about how their effects vary across different land-cover types. This study looked at the interactive effects of land-cover change and microclimate on temporal patterns of soil respiration in a montane forest-grassland-plantation mosaic in a highly diverse but climatically sensitive ecosystem in the tropical Western Ghats of India. Across all vegetation types, soil respiration rates were highest during south-west monsoon (June{\textendash}October), when root growth, litter decomposition and microbial activity are relatively high and were lowest during the summer. Among vegetation types, soil respiration rates were higher in grasslands compared to non-native pine plantations, whereas that of forest and invasive wattle (Acacia mearnsii) plantations were intermediate between grasslands and pine plantations. The decline in respiration rates following conversion from grasslands to pine plantations could be due to relatively lower microbial activity, soil temperatures and, subsequently, slower litter decomposition. In addition, the sensitivity of soil respiration to changes in temperature and moisture differed between different vegetation types. Across all vegetation types, respiration was largely insensitive to changes in soil temperature when moisture levels were low. However, when soil moisture levels were high, respiration increased with temperature in grassland and wattle patches, decreased in the case of pine plantations and remained largely unchanged in shola forests. Our results suggest that changes in aboveground vegetation type can significantly affect soil C cycling even in the absence of any underlying differences in soil type.

}, doi = {10.1017/S0266467424000142}, author = {Joshi, Atul and Ratnam, Jayashree and Paramjyothi, Harinandanan and Sankaran, Mahesh} } @article {142310, title = {Comprehensive phylogeny of Pieridae butterflies reveals strong correlation between diversification and temperature.}, journal = {iScience}, volume = {27}, year = {2024}, month = {2024 Apr 19}, pages = {109336}, abstract = {

Temperature is thought to be a key factor influencing global species richness patterns. We investigate the link between temperature and diversification in the butterfly family Pieridae by combining next generation DNA sequences and published molecular data with fine-grained distribution data. We sampled nearly 600 pierid butterfly species to infer the most comprehensive molecular phylogeny of the family and curated a distribution dataset of more than 800,000 occurrences. We found strong evidence that species in environments with more stable daily temperatures or cooler maximum temperatures in the warm seasons have higher speciation rates. Furthermore, speciation and extinction rates decreased in tandem with global temperatures through geological time, resulting in a constant net diversification.

}, issn = {2589-0042}, doi = {10.1016/j.isci.2024.109336}, author = {Carvalho, Ana Paula S and Owens, Hannah L and St Laurent, Ryan A and Earl, Chandra and Dexter, Kelly M and Messcher, Rebeccah L and Willmott, Keith R and Aduse-Poku, Kwaku and Collins, Steve C and Homziak, Nicholas T and Hoshizaki, Sugihiko and Hsu, Yu-Feng and Kizhakke, Athulya G and Kunte, Krushnamegh and Martins, Dino J and Mega, Nicol{\'a}s O and Morinaka, Sadaharu and Peggie, Djunijanti and Romanowski, Helena P and S{\'a}fi{\'a}n, Szabolcs and Vila, Roger and Wang, Houshuai and Braby, Michael F and Espeland, Marianne and Breinholt, Jesse W and Pierce, Naomi E and Kawahara, Akito Y and Lohman, David J} } @article {149369, title = {Computational analysis of human gut microbial prolyl oligopeptidases (POPs) reveal candidate genes as therapeutics for celiac disease.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 Aug 23}, pages = {19641}, abstract = {

Celiac disease (CD) is a common autoimmune disorder in which the patients are unable to digest gluten, which is present in foods made up of wheat, barley and rye. Whilst diagnosis happens late in 80\% of the cases, avoidance of such foods appears to be the common solution. Alternative management strategies are required for the patients and their families since CD is also genetically carried over. Probiotic therapeutics and the consumption of appropriate enzymes, such as prolyloligopeptidases (POPs), from gut-friendly bacteria could reduce the disease burden and provide a better lifestyle for CD patients. We have examined around 5000 gut bacterial genomes and identified nearly 4000 non-redundant putative POPs. A select set of 10 gut bacterial POP sequences were subject to three-dimensional modelling, ligand docking and molecular dynamics simulations where stable interactions were observed between the POPs and gluten peptides. Our study provides sequence and structural analysis of potential POP enzymes in gut bacterial genomes, which form a strong basis to offer probiotic solutions to CD patients. In particular, these enzymes could be lead future therapeutics for this disease.

}, keywords = {Bacteria, Celiac Disease, Computational Biology, Gastrointestinal Microbiome, Glutens, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Probiotics, Prolyl Oligopeptidases, Serine Endopeptidases}, issn = {2045-2322}, doi = {10.1038/s41598-024-70079-1}, author = {Nayak, Soumya and Regati, Dheemanth Reddy and Sowdhamini, Ramanathan} } @article {147302, title = {Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2.}, journal = {J Mol Biol}, volume = {436}, year = {2024}, month = {2024 Jul 22}, pages = {168716}, abstract = {

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one. Further, this pattern is also observed in therapeutically significant proteins of other ssRNA pandemic viruses, including influenza (HA, NA), spike proteins of Ebola, envelope of Dengue and Chikungunya. We propose that the genetic score serves as an initial indicator, preceding the actual impact of the mutation on viral fitness. Finally, we developed a comprehensive computational pipeline to further explore and predict the subsequent effects of mutations on viral fitness. We believe that our pipeline can narrow down and predict future mutations in therapeutically important viral proteins during a pandemic.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2024.168716}, author = {Sharma, Abhishek and Chandrashekar, C R and Krishna, Sudhir and Sowdhamini, Ramanathan} } @article {149407, title = {Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Oct 03}, pages = {8562}, abstract = {

In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs <= 4.2\%) and concordant (inter-laboratory CVs \< 14\%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

}, keywords = {Calibration, Ceramides, Humans, Laboratories, Lipidomics, Mass Spectrometry, Reference Standards, Reproducibility of Results}, issn = {2041-1723}, doi = {10.1038/s41467-024-52087-x}, author = {Torta, Federico and Hoffmann, Nils and Burla, Bo and Alecu, Irina and Arita, Makoto and Bamba, Takeshi and Bennett, Steffany A L and Bertrand-Michel, Justine and Br{\"u}gger, Britta and Cala, M{\'o}nica P and Camacho-Mu{\~n}oz, Dolores and Checa, Antonio and Chen, Michael and Chocholou{\v s}kov{\'a}, Michaela and Cinel, Michelle and Chu-Van, Emeline and Colsch, Benoit and Coman, Cristina and Connell, Lisa and Sousa, Bebiana C and Dickens, Alex M and Fedorova, Maria and Eir{\'\i}ksson, Finnur Freyr and Gallart-Ayala, Hector and Ghorasaini, Mohan and Giera, Martin and Guan, Xue Li and Haid, Mark and Hankemeier, Thomas and Harms, Amy and H{\"o}ring, Marcus and Hol{\v c}apek, Michal and Hornemann, Thorsten and Hu, Chunxiu and H{\"u}lsmeier, Andreas J and Huynh, Kevin and Jones, Christina M and Ivanisevic, Julijana and Izumi, Yoshihiro and K{\"o}feler, Harald C and Lam, Sin Man and Lange, Mike and Lee, Jong Cheol and Liebisch, Gerhard and Lippa, Katrice and Lopez-Clavijo, Andrea F and Manzi, Malena and Martinefski, Manuela R and Math, Raviswamy G H and Mayor, Satyajit and Meikle, Peter J and Monge, Mar{\'\i}a Eugenia and Moon, Myeong Hee and Muralidharan, Sneha and Nicolaou, Anna and Nguyen-Tran, Thao and O{\textquoteright}Donnell, Valerie B and Ore{\v s}i{\v c}, Matej and Ramanathan, Arvind and Riols, Fabien and Saigusa, Daisuke and Schock, Tracey B and Schwartz-Zimmermann, Heidi and Shui, Guanghou and Singh, Madhulika and Takahashi, Masatomo and Thorsteinsd{\'o}ttir, Margr{\'e}t and Tomiyasu, Noriyuki and Tournadre, Anthony and Tsugawa, Hiroshi and Tyrrell, Victoria J and van der Gugten, Grace and Wakelam, Michael O and Wheelock, Craig E and Wolrab, Denise and Xu, Guowang and Xu, Tianrun and Bowden, John A and Ekroos, Kim and Ahrends, Robert and Wenk, Markus R} } @article {152586, title = {Confronting risks of mirror life.}, journal = {Science}, volume = {386}, year = {2024}, month = {2024 Dec 20}, pages = {1351-1353}, abstract = {

Broad discussion is needed to chart a path forward.

}, keywords = {Artificial Life, Bacteria, Biosecurity, Risk, Stereoisomerism}, issn = {1095-9203}, doi = {10.1126/science.ads9158}, author = {Adamala, Katarzyna P and Agashe, Deepa and Belkaid, Yasmine and Bittencourt, Daniela Matias de C and Cai, Yizhi and Chang, Matthew W and Chen, Irene A and Church, George M and Cooper, Vaughn S and Davis, Mark M and Devaraj, Neal K and Endy, Drew and Esvelt, Kevin M and Glass, John I and Hand, Timothy W and Inglesby, Thomas V and Isaacs, Farren J and James, Wilmot G and Jones, Jonathan D G and Kay, Michael S and Lenski, Richard E and Liu, Chenli and Medzhitov, Ruslan and Nicotra, Matthew L and Oehm, Sebastian B and Pannu, Jaspreet and Relman, David A and Schwille, Petra and Smith, James A and Suga, Hiroaki and Szostak, Jack W and Talbot, Nicholas J and Tiedje, James M and Venter, J Craig and Winter, Gregory and Zhang, Weiwen and Zhu, Xinguang and Zuber, Maria T} } @article {139054, title = {Constrained dynamics of DNA oligonucleotides in phase-separated droplets.}, journal = {Biophys J}, year = {2024}, month = {2024 Jan 02}, abstract = {

Understanding the dynamics of biomolecules in complex environments is crucial for elucidating the effect of condensed and heterogeneous environments on their functional properties. A relevant environment-and one that can also be mimicked easily in\ vitro-is that of phase-separated droplets. While phase-separated droplet systems have been shown to compartmentalize a wide range of functional biomolecules, the effects of internal structuration of droplets on the dynamics and mobility of internalized molecules remain poorly understood. Here, we use fluorescence correlation spectroscopy to measure the dynamics of short oligonucleotides encapsulated within two representative kinds of uncharged and charged phase-separated droplets. We find that the internal structuration controls the oligonucleotide dynamics in these droplets, revealed by measuring physical parameters at high spatiotemporal resolution. By varying oligonucleotide length and salt concentrations (and thereby charge screening), we found that the dynamics are significantly affected in the noncharged droplets compared to the charged system. Our work lays the foundation for unraveling and quantifying the physical parameters governing biomolecular transport in the condensed environment.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2023.12.025}, author = {Singh, Anupam and Thutupalli, Shashi and Kumar, Manoj and Ameta, Sandeep} } @article {150941, title = {The cost of cellular patterns}, journal = {Nature Physics}, volume = {20}, year = {2024}, month = {10/2024}, pages = {1704{\textendash}1705}, abstract = {

The cell cortex consists of a chemical and a mechanical subsystem, but how energy is allocated between them is unknown. Now, measurements of the entropy production rate have revealed what determines the cell cortex{\textquoteright}s energy budget.

}, doi = {10.1038/s41567-024-02687-7}, author = {Thutupalli, Shashi} } @article {145435, title = {Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {04/2024}, pages = {2942}, chapter = {1}, abstract = {

Pannexins are single-membrane large-pore channels that release ions and ATP upon activation. Three isoforms of pannexins 1, 2, and 3, perform diverse cellular roles and differ in their pore lining residues. In this study, we report the cryo-EM structure of pannexin 3 at 3.9 {\r A} and analyze its structural differences with pannexin isoforms 1 and 2. The pannexin 3 vestibule has two distinct chambers and a wider pore radius in comparison to pannexins 1 and 2. We further report two cryo-EM structures of pannexin 1, with pore substitutions W74R/R75D that mimic the pore lining residues of pannexin 2 and a germline mutant of pannexin 1, R217H at resolutions of 3.2 {\r A} and 3.9 {\r A}, respectively. Substitution of cationic residues in the vestibule of pannexin 1 results in reduced ATP interaction propensities to the channel. The germline mutant R217H in transmembrane helix 3 (TM3), leads to a partially constricted pore, reduced ATP interaction and weakened voltage sensitivity. The study compares the three pannexin isoform structures, the effects of substitutions of pore and vestibule-lining residues and allosteric effects of a pathological substitution on channel structure and function thereby enhancing our understanding of this vital group of ATP-release channels.

}, doi = {10.1038/s41467-024-47142-6}, author = {Hussain, N and Apotikar, A and Pidathala, S and Mukherjee, S and Burada, AP and Sikdar, SK and Vinothkumar, KR and Penmatsa, A} } @article {140656, title = {Cuticular Hydrocarbon Profiles of Himalayan Bumble Bees (Hymenoptera: Bombus Latreille) are Species-Specific and Show Elevational Variation.}, journal = {J Chem Ecol}, year = {2024}, month = {2024 Mar 12}, abstract = {

Bumble bees are important pollinators in natural environments and agricultural farmlands, and they are in particular adapted to harsh environments like high mountain habitats. In these environments, animals are exposed to low temperature and face the risk of desiccation. The Eastern Himalayas are one of the recognized biodiversity hotspots worldwide. The area covers subtropical rainforest with warm temperature and high precipitation as well as high mountain ranges with peaks reaching up to 7,000\ m, shaping a diverse floral and faunal community at the different elevational zones. To identify possible adaptation strategies, we investigated the cuticular hydrocarbon profiles of four bumble bee species occurring at different elevational ranges in Arunachal Pradesh, the northeastern most state in India. At 17 locations along an elevational gradient, we collected workers of two species from lower elevations (B. albopleuralis and B. breviceps; ~ 100\ m - 3,000\ m asl) and two species from higher elevations (B. prshewalskyi and B. mirus; ~ 2,800\ m - 4,500\ m asl). The CHC profiles of all four species showed a significant degree of variation in the composition of hydrocarbons, indicating species specificity. We also found clear correlation with elevation. The weighted mean chain length of the hydrocarbons significantly differed between the low and high elevation species, and the proportion of saturated hydrocarbons in CHC profiles significantly increased with the elevational range of the bumble bee species. Our results indicate that bumble bees living at high elevations reduce the risk of water loss by adapting their CHC composition on their cuticle, a phenomenon that has also been found in other insects like ants and fruit flies.

}, issn = {1573-1561}, doi = {10.1007/s10886-024-01486-x}, author = {Narah, Jaya and Streinzer, Martin and Chakravorty, Jharna and Megu, Karsing and Spaethe, Johannes and Brockmann, Axel and Schmitt, Thomas} } @article {152137, title = {Description of Protosticta khasia sp. nov. and Yunnanosticta siangi sp. nov., with new records of P. samtsensis Gurung \& Phan, 2023 from Northeast India (Odonata: Zygoptera: Platystictidae).}, journal = {Zootaxa}, volume = {5448}, year = {2024}, month = {2024 May 13}, pages = {348-370}, abstract = {

Protosticta Selys is a genus of damselflies of the family Platystictidae Kennedy found in forests of tropical Southeast Asia. The genus Protosticta has rarely been reported from Northeast India. In this paper, we describe Protosticta khasia sp. nov. (subfamily Protostictinae Dijkstra et al.) based on holotype male and paratype female collected from Maraikaphon, East Khasi Hills district, Meghalaya, India. Protosticta khasia can be identified by the markings of the prothorax and the shape of the male paraproct with two arms. We also describe Yunnanosticta siangi sp. nov. (subfamily Sinostictinae Wilson) from Arunachal Pradesh, India, based on two males and two females. This species is differentiated from its congeners by the thoracic and abdominal markings as well as the shape of male caudal appendages. The key for males of Yunnanosticta is provided. Additionally, we provide new records of Protosticta samtsensis Gurung \& Phan, along with an updated key to the Protosticta species of Northeast India.

}, keywords = {Animal Distribution, Animal Structures, Animals, Body Size, Ecosystem, Female, India, Male, Odonata, Organ Size}, issn = {1175-5334}, doi = {10.11646/zootaxa.5448.3.2}, author = {Joshi, Shantanu and Sarkar, Vivek and Sawant, Dattaprasad and Pawar, Ujwala and Kunte, Krushnamegh} } @article {144784, title = {Design approaches for 3D cell culture and 3D bioprinting platforms.}, journal = {Biophys Rev (Melville)}, volume = {5}, year = {2024}, month = {2024 Jun}, pages = {021304}, abstract = {

The natural habitat of most cells consists of complex and disordered 3D microenvironments with spatiotemporally dynamic material properties. However, prevalent methods of culture study cells under poorly biomimetic 2D confinement or homogeneous conditions that often neglect critical topographical cues and mechanical stimuli. It has also become increasingly apparent that cells in a 3D conformation exhibit dramatically altered morphological and phenotypical states. In response, efforts toward designing biomaterial platforms for 3D cell culture have taken centerstage over the past few decades. Herein, we present a broad overview of biomaterials for 3D cell culture and 3D bioprinting, spanning both monolithic and granular systems. We first critically evaluate conventional monolithic hydrogel networks, with an emphasis on specific experimental requirements. Building on this, we document the recent emergence of microgel-based 3D growth media as a promising biomaterial platform enabling interrogation of cells within porous and granular scaffolds. We also explore how jammed microgel systems have been leveraged to spatially design and manipulate cellular structures using 3D bioprinting. The advent of these techniques heralds an unprecedented ability to experimentally model complex physiological niches, with important implications for tissue bioengineering and biomedical applications.

}, issn = {2688-4089}, doi = {10.1063/5.0188268}, author = {Sreepadmanabh, M and Arun, Ashitha B and Bhattacharjee, Tapomoy} } @article {152135, title = {Devadatta adii sp. nov. (Odonata: Zygoptera: Devadattidae) from Upper Siang District, Arunachal Pradesh, India.}, journal = {Zootaxa}, volume = {5519}, year = {2024}, month = {2024 Oct 10}, pages = {571-589}, abstract = {

We erect a new species Devadatta adii sp. nov. based on five males and five females collected from Upper Siang District, Arunachal Pradesh, India. The males of the new taxon are unique in terms of having a golden yellow lateral pterothorax, strongly curved cerci and filamentous genital ligula. We also provide illustrations of male thorax and caudal appendages of Devadatta spp..

}, keywords = {Animal Distribution, Animal Structures, Animals, Body Size, Female, India, Male, Odonata, Organ Size}, issn = {1175-5334}, doi = {10.11646/zootaxa.5519.4.6}, author = {Sawant, Dattaprasad and Joshi, Shantanu and Pawar, Ujwala and Naik, Pratiksha and Khan, Fahim and Nawge, Viraj and Kunte, Krushnamegh} } @article {149950, title = {Devadatta adii sp. nov. (Odonata: Zygoptera: Devadattidae) from Upper Siang District, Arunachal Pradesh, India}, journal = {ZOOTAXA}, volume = {5519}, year = {2024}, month = {10/2024}, pages = {571-589}, abstract = {

We erect a new species Devadatta adii sp. nov. based on five males and five females collected from Upper Siang District, Arunachal Pradesh, India. The males of the new taxon are unique in terms of having a golden yellow lateral pterothorax, strongly curved cerci and filamentous genital ligula. We also provide illustrations of male thorax and caudal appendages of Devadatta spp..

}, doi = {10.11646/zootaxa.5519.4.6}, author = {Sawant, Dattaprasad and Joshi, Shantanu and Pawar, Ujwala and Naik, Pratiksha and Khan, Fahim and Nawge, Viraj and Kunte, Krushnamegh} } @article {149384, title = {Development of pial collaterals by extension of pre-existing artery tips.}, journal = {Cell Rep}, volume = {43}, year = {2024}, month = {2024 Sep 24}, pages = {114771}, abstract = {

Pial collaterals provide protection from ischemic damage and improve the prognosis of stroke patients. The origin or precise sequence of events underlying pial collateral development is unclear and has prevented clinicians from adapting new vascularization and regeneration therapies. We use genetic lineage tracing and intravital imaging of mouse brains at cellular resolution to show that during embryogenesis, pial collateral arteries develop from extension and anastomoses of pre-existing artery tips in a VegfR2-dependent manner. This process of artery tip extension occurs on pre-determined microvascular tracks. Our data demonstrate that an arterial receptor, Cxcr4, earlier shown to drive artery cell migration and coronary collateral development, is dispensable for the formation and maintenance of pial collateral arteries. Our study shows that collateral arteries of the brain are built by a mechanism distinct from that of the heart.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2024.114771}, author = {Kumar, Suraj and Ghosh, Swarnadip and Shanavas, Niloufer and Sivaramakrishnan, Vinayak and Dwari, Manish and Das, Soumyashree} } @article {150940, title = {Did the Deccan Volcanism impact the Indian flora during the Maastrichtian?}, journal = {EARTH-SCIENCE REVIEWS}, volume = {258}, year = {2024}, month = {11/2024}, abstract = {

The Deccan-associated sediments (Lameta and intertrappean deposits) hold great potential for understanding the role of Deccan Volcanism in the late Maastrichtian ecological upheaval. However, it is challenging to ascertain Deccan Volcanism driven floral changes on the Indian Plate due to unresolvedstratigraphyic and lack of well-dated terrestrial sequences. We provide a thorough palaeobotanical, palaeoclimatic and palaeobiogeographic review of the pre-Deccan (Lameta deposits) and syn-Deccan (intertrappean deposits) sequences. We present a detailed palynological analysis of C29R magnetochron intertrappean section from Yeotmal, central India, depicting episodic regional floral responses to volcanism. We have critically reviewed the Indian Maastrichtian palaeofloral and palaeoclimatic records within the best-resolved chronologies to clarify the spatiotemporal changes in palaeovegetation and palaeoclimate pertaining to the Deccan Volcanism. Furthermore, we evaluated the global fossil records of all the nearest living relatives of the studied assemblage to enhance our understanding of the genesis of the late Maastrichtian flora of the Deccan Volcanic Province.

Our study showcases three stages of the Maastrichtian floral succession, corresponding to a quiescent phase between two secondary magmatic pulses of the C29R Magnetochron. Palaeowildfires and massive magmatic outflow caused by the active volcanism severely damaged the pre-existing flora. Progressively, confined and diminished volcanism at Stage-I allowed few aquatic and herbaceous species to flourish within the accessible lacustrine habitats. The dormant volcanic activity at Stage-II, in conjunction with the warm (MAT- similar to 26 degrees C) and moist (MAP- similar to 2270 mm) conditions due to latitudinal shifting of the Indian Plate within the Inter Tropical Convergence Zone, facilitated rapid expansion and diversification of the low-lying megathermal angiosperm forest within various habitats along shallow embayments. The gradual resurgence of volcanic activity at Stage-III resulted in widespread wildfires and forest knockdowns. The swift revival of the hyper-diverse tropical flora during the quiescent phase (Stage-II) does not show long-term (millennial scale) adverse impact of the Deccan Volcanism on the Indian Maastrichtian flora. The palaeobotanical and palaeoclimatic review suggests a consistent subtropical to tropical climate on the Indian Plate during the late Maastrichtian. However, a shift in seasonality from a seasonally dry climate supporting gymnosperm-angiosperm flora during the pre-Deccan phase to a seasonally wet climate and angiosperm-dominated flora during the syn-Deccan phase is noticeable. Furthermore, the palaeobiogeographic analysis suggests that much of the Maastrichtian biodiversity on the Indian Plate is a consequence of floral influx from South America and Africa via the Kohistan-Ladakh Island arc. Nonetheless, 41.2 \% of the palaeoendemic taxa in the studied palynoassemblage signify substantial in-situ evolution and diversification of tropical angiosperms on the Indian Plate. Consequently, the observed floral and climatic changes during the Maastrichtian period should not solely be attributed to the Deccan Volcanism but to a combination of variables. These include the shifting of the Indian Plate within the Inter Tropical Convergence Zone, enhanced warm and humid climate due to high CO2 emissions, episodic nature of the Deccan Volcanism, persistence of rich spore and seed stock in legacy flora, better physiological adaptibility of angiosperms for wet climate regimes and tropical floral influx from contiguous biotic corridor.

}, doi = {10.1016/j.earscirev.2024.104950}, author = {Mishra, Shreya and Bansal, Mahi and Prasad, Vandana and Singh, Vikram Partap and Murthy, Srikanta and Parmar, Shalini and Utescher, Torsten and Khangar, Ranjit} } @article {145425, title = {Differentially biased sampling strategies reveal the non-stationarity of species distribution models for Indian small felids}, journal = {ECOLOGICAL MODELLING}, volume = {493}, year = {2024}, month = {06/2024}, abstract = {

Species Distribution Models (SDMs) have been used extensively to understand species-habitat relationships and design conservation strategies. The ability to train these models using a wide variety of datasets and modelling algorithms has led to their wide applicability across systems. However, the ease of modelling also leads to their use as off-the-shelf models without a detailed investigation of the data and their suitable end-use application. The effect of various modelling parameters on inferences has been explored, however, their interaction with training data type is limited. We used country-wide data for four sympatric Indian small cat species to understand the sensitivity of SDMs to data types, sampling extents and their interaction. Our results reveal the non-stationarity of models with varying modelling parameters. The extent of the training dataset had major implications on the inferences and interacted strongly with the type of dataset used. The divergent distribution of the target species revealed that the effect of sampling extent was more pronounced for species that have limited distribution within the predictive extent. Lastly, our results highlight the significance of sampled environmental space in explaining the non-stationarity of the model outputs.

}, doi = {10.1016/j.ecolmodel.2024.110749}, author = {Rana, Divyashree and Sartor, CC and Chiaverini, Luca and Cushman, SA and Kaszta, Z and Ramakrishnan, U. and Macdonald, David W.} } @article {140639, title = {Distinct developmental patterns in Anopheles stephensi organ systems.}, journal = {Dev Biol}, volume = {508}, year = {2024}, month = {2024 Apr}, pages = {107-122}, abstract = {

Anatomical profiles of insects inform vector biology, comparative development and evolutionary studies with applications in forensics, agriculture and disease control. This study presents a comprehensive, high-resolution developmental profile of Anopheles stephensi, encompassing larval, pupal, and adult stages, obtained through microCT scanning. The results indicate in situ anatomical changes in most organ systems, including the central nervous system, eyes, musculature, alimentary canal, salivary glands, and ovaries, among other organ systems, except for the developing heart. We find significant differences in the mosquito gut, body-wall, and flight muscle development during metamorphosis from other dipterans like Drosophila. Specifically, indirect flight muscle specification and growth can be traced back at least to the 4th instar A. stephensi larvae, as opposed to post-puparial development in other Dipterans like Drosophila and Calliphora. Further, while Drosophila larval body-wall muscles and gut undergo histolysis, changes to these organs during mosquito metamorphosis are less pronounced. These observations, and raw data therein may serve as a reference for studies on the development and the genetics of mosquitoes. Overall, the detailed developmental profile of A. stephensi presented here illuminates the unique anatomy and developmental processes of Culicidae, with important implications for vector biology, disease control, and comparative evolutionary studies.

}, keywords = {Animals, Anopheles, Drosophila, Larva, Mosquito Vectors}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2024.01.008}, author = {Agrawal, Khushboo and Prabhakar, Sunil and Bakthavachalu, Baskar and Chaturvedi, Dhananjay} } @article {149953, title = {Divergence and convergence in epiphytic and endophytic phyllosphere bacterial communities of rice landraces.}, journal = {mSphere}, year = {2024}, month = {2024 Oct 30}, pages = {e0076524}, abstract = {

Phyllosphere-associated microbes can significantly alter host plant fitness, with distinct functions provided by bacteria inhabiting the epiphytic (external surface) vs endophytic niches (internal leaf tissue). Hence, it is important to understand the assembly and stability of these phyllosphere communities, especially in field conditions. Broadly, epiphytic communities should encounter more environmental fluctuations and frequent immigration, whereas endophytic microbiota should face stronger host selection. As a result, we expect greater variability in epiphytic than endophytic communities. We analyzed the structure and stability of leaf phyllosphere microbiota of four traditionally cultivated rice landraces and one commercial variety from northeast India grown in the field for 3 consecutive years, supplemented with opportunistic sampling of eight other landraces. Epiphytic and endophytic bacterial communities shared dominant core genera such as and . Consistent with an overall strong environmental effect, both communities varied more across sampling years than across host landraces. Seeds sampled from a focal landrace did not support vertical transmission of phyllosphere bacteria, suggesting that both types of communities are assembled anew each generation. Despite these points of convergence, epiphytic communities had distinct composition and significantly higher microbial load and were more rich, diverse, modular, and unstable than endophytic communities. Finally, focused sampling of one landrace across developmental stages showed that the divergence between the two types of communities arose primarily at the flowering stage. Thus, our results show both convergent and divergent patterns of community assembly and composition in distinct phyllosphere niches in rice, identifying key bacterial genera and host developmental stages that may aid agricultural interventions to increase rice yield.IMPORTANCEPhyllosphere (leaf-associated) microbes significantly impact plant fitness, making it crucial to understand how these communities are assembled and maintained. While many studies have analyzed epiphytic (surface) phyllosphere communities, we have a relatively poor understanding of endophytic communities which colonize the very distinct niche formed inside leaf tissues. We found that across several rice landraces, both communities are largely colonized by the same core genera, indicating divergence at the species level across the two leaf niches and highlighting the need to understand the mechanisms underlying this divergence. Surprisingly, both epiphytic and endophytic communities were only weakly shaped by the host landrace, with a much greater role for environmental factors that likely vary over time. Thus, microbiome-based agricultural interventions for increasing productivity could perhaps be generalized across rice varieties but would need to account for the temporal instability of the microbiota. Our results thus highlight the importance of data sets such as ours-with extensive sampling across landraces and years-for understanding phyllosphere microbiota and their applications in the field.

}, issn = {2379-5042}, doi = {10.1128/msphere.00765-24}, author = {Sanjenbam, Pratibha and Agashe, Deepa} } @article {149386, title = {Divergence and serial colonization shape genetic variation and define conservation units in Asian elephants.}, journal = {Curr Biol}, year = {2024}, month = {2024 Sep 27}, abstract = {

Asian elephants (Elephas maximus) are the largest extant terrestrial megaherbivores native to Asia, with 60\% of their wild population found in India. Despite ecological and cultural importance, their population genetic structure and diversity, demographic history, and ensuing implications for management/conservation remain understudied. We analyzed 34 whole genomes (between 11{\texttimes} and 32{\texttimes}) from most known elephant landscapes in India and identified five management/conservation units corresponding to elephants in Northern (Northwestern/Northeastern), Central, and three in Southern India. Our data reveal signatures of divergence and serial colonization and a potential dilution of genetic diversity from north to south of India. The northern populations diverged from others more than 70,000 years ago, have higher genetic diversity, and have low inbreeding (pi\ = 0.0016\ {\textpm} 0.0001; F\ = 0.09\ {\textpm} 0.03). Two of three populations in Southern India have low diversity and are inbred, with very low effective population sizes compared with census sizes (pi\ = 0.0014\ {\textpm} 0.00009 and 0.0015\ {\textpm} 0.0001; F\ = 0.25\ {\textpm} 0.09 and 0.17\ {\textpm} 0.02). Analyses of genetic load reveal the purging of potentially high-effect insertion/deletion (indel) deleterious alleles in the southern populations and a decreasing number of deleterious alleles from north to south in India. However, despite dilution and purging for the damaging mutation load in Southern India, the load that remains is homozygous. High homozygosity of deleterious alleles, coupled with low neutral genetic diversity, make southernmost populations high priority for conservation attention. Most surprisingly, our study suggests that patterns of genetic diversity and genetic load can correspond to genomic signatures of serial founding events, even in large, highly mobile, endangered mammals.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2024.08.062}, author = {Khan, Anubhab and Sil, Maitreya and Thekaekara, Tarsh and Garg, Kritika M and Sinha, Ishani and Khurana, Rupsy and Sukumar, Raman and Ramakrishnan, Uma} } @article {147295, title = {DNA barcodes from over-a-century-old type specimens shed light on the taxonomy of a group of rare butterflies (Lepidoptera: Nymphalidae: Calinaginae).}, journal = {PLoS One}, volume = {19}, year = {2024}, month = {2024}, pages = {e0305825}, abstract = {

We analyzed COI barcode sequences from 138 over-a-century old specimens of Calinaga including 36 name-bearing type specimens stored at the Natural History Museum London. These new data, combined with previously available RPS5 sequences, divide the Calinaga samples into four well-supported mitochondrial lineages that together with a novel wing-pattern analysis, support the recognition of six species (lhatso, buddha, brahma, aborica, formosana and davidis), with all other names subsumed either as subspecies or synonyms. One new taxon is described, Calinaga aborica naima Vane-Wright, ssp. n.

}, keywords = {Animals, Butterflies, DNA Barcoding, Taxonomic, Electron Transport Complex IV, Phylogeny, Wings, Animal}, issn = {1932-6203}, doi = {10.1371/journal.pone.0305825}, author = {Todisco, Valentina and Basu, Dipendra Nath and Prosser, Sean W J and Russell, Stephen and Mutanen, Marko and Zilli, Alberto and Huertas, Blanca and Kunte, Krushnamegh and Vane-Wright, Richard} } @article {142306, title = {Dynamic clustering of active rings}, journal = {Phys. Rev. Research}, volume = {6}, year = {2024}, month = {02/2024}, abstract = {

A collection of rings made of active Brownian particles (ABPs) for different packing fractions and activities is investigated using computer simulations. We show that active rings display an emergent dynamic clustering instead of the conventional motility-induced phase separation (MIPS) as in the case of collection of ABPs. Surprisingly, increasing packing fraction of rings exhibits a nonmonotonicity in the dynamics due to the formation of a large number of small clusters. The conformational fluctuations of the polymers suppress the usual MIPS exhibited by ABPs. Our findings demonstrate how the motion of a collection of rings is influenced by the interplay of activity, topology, and connectivity.

}, doi = {10.1103/PhysRevResearch.6.L012038}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {147291, title = {Early Detection of KP.2 SARS-CoV-2 Variant using Wastewater-based Genomic Surveillance in Pune, Maharashtra, India.}, journal = {J Travel Med}, year = {2024}, month = {2024 Jul 17}, issn = {1708-8305}, doi = {10.1093/jtm/taae097}, author = {Rajput, Vinay and Das, Rashmita and Pramanik, Rinka and Nannaware, Kiran and Sushma, Y and Taji, Nyabom and Rajput, Vishal and Rajkhowa, Riyakshi and Pacharne, Poonam and Shah, Priyanki and Gogate, Niharika and Sangwar, Poornima and Bhalerao, Asim and Jain, Nidhi and Kamble, Sanjay and Dastager, Syed and Shashidhara, L S and Karyakarte, Rajesh and Dharne, Mahesh} } @article {145416, title = {Ecofriendly agriculture pest control using pheromone packed programed nanovolcanoes framed by graphene oxide}, journal = {CLEAN TECHNOLOGIES AND ENVIRONMENTAL POLICY}, year = {2024}, month = {05/2024}, abstract = {

Ecofriendly agricultural practices encourage pheromone usage, but cost is a major limitation for pheromone-based techniques. Hence, various slow-release technologies have been developed to provide-controlled release, reducing the cost of source compounds. Here, we have identified a graphene oxide edifice that allows the controlled release of a complex pheromone cocktail with compounds having different polarities through ratio-metric molecular pockets. These pockets resemble liquid crystals and show both controlled release as well as stimulus-responsive burst release without charring. These properties are beneficial for pest control.

}, doi = {10.1007/s10098-024-02861-8}, author = {Kaur, Kamaljit and Chandel, Mahima and Munikrishnappa, VKT and Kumar, Prem and Sahu, BK and Ahamed, Momin and Manjunath, Sowmya and Gorantla, Markandeya and Olsson, Shannon and Muthusamy, Eswaramoorthy and Subaharan, Kesavan and Shanmugam, Vijayakumar} } @article {144789, title = {Emergent dynamics due to chemo-hydrodynamic self-interactions in active polymers.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Jun 08}, pages = {4903}, abstract = {

The field of synthetic active matter has, thus far, been led by efforts to create point-like, isolated (yet interacting) self-propelled objects (e.g. colloids, droplets, microrobots) and understanding their collective dynamics. The design of flexible, freely jointed active assemblies from autonomously powered sub-components remains a challenge. Here, we report freely-jointed active polymers created using self-propelled droplets as monomeric units. Our experiments reveal that the self-shaping chemo-hydrodynamic interactions between the monomeric droplets give rise to an emergent rigidity (the acquisition of a stereotypical asymmetric C-shape) and associated ballistic propulsion of the active polymers. The rigidity and propulsion of the chains vary systematically with their lengths. Using simulations of a minimal model, we establish that the emergent polymer dynamics are a generic consequence of quasi two-dimensional confinement and auto-repulsive trail-mediated chemical interactions between the freely jointed active droplets. Finally, we tune the interplay between the chemical and hydrodynamic fields to experimentally demonstrate oscillatory dynamics of the rigid polymer propulsion. Altogether, our work highlights the possible first steps towards synthetic self-morphic active matter.

}, issn = {2041-1723}, doi = {10.1038/s41467-024-49155-7}, author = {Kumar, Manoj and Murali, Aniruddh and Subramaniam, Arvin Gopal and Singh, Rajesh and Thutupalli, Shashi} } @article {144803, title = {Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder.}, journal = {Mol Autism.}, volume = {15}, year = {2024}, month = {06/24}, pages = {28}, abstract = {

Background: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5-/y rats.

Methods: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology.

Results: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses.

Conclusions: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity.

Limitations: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.

}, doi = {doi: 10.1186/s13229-024-00601-9}, author = {Sim{\~o}es, de Oliveira L and O{\textquoteright}Leary, HE and Nawaz, S and Loureiro, R and Davenport, EC and Baxter, P and Louros, SR and Dando, O and Perkins, E and Peltier, J and Trost, M and Osterweil, EK and Hardingham, GE and Cousin, MA and Chattarji, S and Booker, SA and Benke, TA and Wyllie, DJA and Kind, PC} } @article {149409, title = {Evolutionary Adaptation in Heterogeneous and Changing Environments.}, journal = {Evolution}, year = {2024}, month = {2024 Oct 09}, abstract = {

Organisms that are adapting to long term environmental change almost always deal with mul- tiple environments and trade-offs that affect their optimal phenotypic strategy. Here we combine the idea of repeated variation or heterogeneity, like seasonal shifts, with long-term directional dy- namics. Using the framework of fitness sets, we determine the dynamics of the optimal phenotype in two competing environments encountered with different frequencies, one of which changes with time. When such an optimal strategy is selected for in simulations of evolving populations, we observe rich behavior that is qualitatively different from and more complex than adaptation to long-term change in a single environment. The probability of survival and the critical rate of environmental change above which populations go extinct depend crucially on the relative fre- quency of the two environments and the strength and asymmetry of their selection pressures. We identify a critical frequency for the stationary environment, above which populations can escape the pressure to constantly evolve by adapting to the stationary optimum. In the neighborhood of this critical frequency, we also find the counter-intuitive possibility of a lower bound on the rate of environmental change, below which populations go extinct, and above which a process of evolutionary rescue is possible.

}, issn = {1558-5646}, doi = {10.1093/evolut/qpae144}, author = {Chaturvedi, Nandita and Chatterjee, Purba} } @article {150946, title = {Experimental Evolution Induced by Maternal Post-copulatory Factors in Drosophila.}, journal = {Behav Genet}, year = {2024}, month = {2024 Nov 21}, abstract = {

Experimental evolution is a powerful approach to study the mechanisms underlying the adaptation of selected characters under the conditions chosen in the laboratory. Drosophila melanogaster is a species frequently used to investigate the experimental evolution of characters, especially those related to reproduction. Recent intra-generational studies showed that cis-vaccenyl acetate (cVa), a sex pheromone transferred with bacteria on eggs by females either 1\ day (D1) or 5\ days (D5) after copulation, differentially affected the behavior and pheromone release in adult males emerging from these eggs. Here, we extended this finding to determine whether this alternative egg exposure repeated over many generations could affect a larger set of reproduction-related characters in both sexes. To test the repetitive effects of maternal D1 or D5 post-copulatory factors, we carried out an experimental selection procedure consisting of exposing eggs during 40 successive generations to D1 or D5 maternal post-copulatory factors. We compared cVa and cuticular pheromones, courtship and mating behaviors, and fecundity at different generations in flies of D1 and D5 lines. Based on findings obtained at earlier generations, we also determined survival, bacterial composition and gene expression in adults. Some of these complex traits significantly diverged between D1 and D5 lines indicating that maternal post-copulatory factors transmitted to eggs can influence adult life history traits.

}, issn = {1573-3297}, doi = {10.1007/s10519-024-10206-w}, author = {Jean-Fran{\c c}ois, Ferveur and Pratibha, Sanjenbam and St{\'e}phane, Fraichard and Enisa, Aru{\c c}i and Fabrice, Neiers and Bernard, Moussian and Deepa, Agashe and Claude, Everaerts} } @article {142307, title = {Explore before you restore: Incorporating complex systems thinking in ecosystem restoration}, journal = {JOURNAL OF APPLIED ECOLOGY }, year = {2024}, month = {03/2024}, abstract = {

1. The global movement for ecosystem restoration has gained momentum in response to the Bonn Challenge (2010) and the UN Decade on Ecosystem Restoration (UNDER, 2021-2030). While several science-based guidelines exist to aid in achieving successful restoration outcomes, significant variation remains in the outcomes of restoration projects. Some of this disparity can be attributed to unexpected responses of ecosystem components to planned interventions.

2. Given the complex nature of ecosystems, we propose that concepts from Complex Systems Science (CSS) that are linked to non-linearity, such as regime shifts, ecological resilience and ecological feedbacks, should be employed to help explain this variation in restoration outcomes from an ecological perspective.

3. Our framework, Explore Before You Restore, illustrates how these concepts impact restoration outcomes by influencing degradation and recovery trajectories. Additionally, we propose incorporating CSS concepts into the typical restoration project cycle through a CSS assessment phase and suggest that the need for such assessment is explicitly included in the guidelines to improve restoration outcomes.

4. To facilitate this inclusion and make it workable by practitioners, we describe indicators and methods available for restoration teams to answer key questions that should make up such CSS assessment. In doing so, we identify key outstanding science and policy tasks that are needed to further operationalize CSS assessment in restoration.

5. Synthesis and applications. By illustrating how key Complex Systems Science (CSS) concepts linked to non-linear threshold behaviour can impact restoration outcomes through influencing recovery trajectories, our framework Explore Before You Restore demonstrates the need to incorporate Complex Systems thinking in ecosystem restoration. We argue that inclusion of CSS assessment into restoration project cycles, and more broadly, into international restoration guidelines, may significantly improve restoration outcomes.

}, doi = { https://doi.org/10.1111/1365-2664.14614}, author = {Maes, S. L. and Perring, M. P. and Cohen, R. and Akinnifesi, F. K. and Bargues-Tobella, A. and Bastin, J. -f. and Bauters, M. and Bernardino, P. N. and Brancalion, P. H. S. and Bullock, J. M. and Ellison, D. and Fayolle, A. and Fremout, T. and Gann, G. D. and Hishe, H. and Holmgren, M. and Ilstedt, U. and Mahy, G. and Messier, C. and Parr, C. L. and Ryan, C. M. and Sacande, M. and Sankaran, M. and Scheffer, M. S. and Suding, K. N. and Van Meerbeek, K. and Verbeeck, H. and Verbist, B. J. P. and Verheyen, K. and Winowiecki, L. A. and Muys, B.} } @article {140645, title = {Exploring advances in single particle CryoEM with apoferritin: From blobs to true atomic resolution.}, journal = {Int J Biochem Cell Biol}, volume = {169}, year = {2024}, month = {2024 Feb 01}, pages = {106536}, abstract = {

Deciphering the three-dimensional structures of macromolecules is of paramount importance for gaining insights into their functions and roles in human health and disease. Single particle cryoEM has emerged as a powerful technique that enables direct visualization of macromolecules and their complexes, and through subsequent averaging, achieve near atomic-level resolution. A major breakthrough was recently achieved with the determination of the apoferritin structure at true atomic resolution. In this review, we discuss the latest technological innovations across the entire single-particle workflow, which have been instrumental in driving the resolution revolution and in transforming cryoEM as a mainstream technique in structural biology. We illustrate these advancements using apoferritin as an example that has served as an excellent benchmark sample for assessing emerging technologies. We further explore whether the existing technology can routinely generate atomic structures of dynamic macromolecules that more accurately represent real-world samples, the limitations in the workflow, and the current approaches employed to overcome them.

}, issn = {1878-5875}, doi = {10.1016/j.biocel.2024.106536}, author = {Premageetha, Gowtham ThambraRajan and Vinothkumar, Kutti R and Bose, Sucharita} } @article {145423, title = {Exploring oil absorption and distribution in immersion-fried pantoa (Indian dairy dessert): effects of frying media}, journal = {Journal of Food Science and Technology}, year = {2024}, month = {06/2024}, abstract = {

The kinetics, oil migration pattern and the role of frying media during immersion frying of {\textquoteright}pantoa{\textquoteright}, a dairy dessert, at the microstructural level were studied using confocal laser scanning microscopy (CLSM). After 6 min of frying, the depth of oil migration in pantoa increased from 0 to 3.16 mm in clarified butter (locally called {\textquoteright}ghee{\textquoteright}) and 3.81 mm in sunflower oil. Migration was 1.6 times higher and 1.25 times deeper in pantoa fried in sunflower oil than in clarified butter because of higher moisture loss and pore development. The near absence of fluorescence in the CLSM images of pantoa core evidenced that oil did not penetrate the core. Moisture loss and oil migration (fat uptake) were strongly correlated (r = 0.99). CLSM and optical scan images established that oil migrated into pantoa only at the end of frying. Thus, frying of pantoa in clarified butter would be better in terms of minimizing fat migration. The extent and depth of oil migration in the crust and core of pantoa in sunflower oil and clarified butter have been mapped, quantified and compared. This study helps to instantiate the oil/fat migration process in complex and dense fried foods. Also, it will be relevant for the food industry in terms of optimizing the fat content of fried products, thereby avoiding excess oil and produce healthy foods of desired quality.

}, doi = {10.1007/s13197-024-06018-9}, author = {Neethu, K. C. and Pushpadass, Heartwin A. and Franklin, MEE and Krishnamurthy, H.} } @article {145428, title = {Factors affecting macromolecule orientations in thin films formed in cryo-EM.}, journal = {Acta Crystallogr D Struct Biol}, volume = {80}, year = {2024}, month = {2024 Jul 01}, pages = {535-550}, abstract = {

The formation of a vitrified thin film embedded with randomly oriented macromolecules is an essential prerequisite for cryogenic sample electron microscopy. Most commonly, this is achieved using the plunge-freeze method first described nearly 40 years ago. Although this is a robust method, the behaviour of different macromolecules shows great variation upon freezing and often needs to be optimized to obtain an isotropic, high-resolution reconstruction. For a macromolecule in such a film, the probability of encountering the air-water interface in the time between blotting and freezing and adopting preferred orientations is very high. 3D reconstruction using preferentially oriented particles often leads to anisotropic and uninterpretable maps. Currently, there are no general solutions to this prevalent issue, but several approaches largely focusing on sample preparation with the use of additives and novel grid modifications have been attempted. In this study, the effect of physical and chemical factors on the orientations of macromolecules was investigated through an analysis of selected well studied macromolecules, and important parameters that determine the behaviour of proteins on cryo-EM grids were revealed. These insights highlight the nature of the interactions that cause preferred orientations and can be utilized to systematically address orientation bias for any given macromolecule and to provide a framework to design small-molecule additives to enhance sample stability and behaviour.

}, keywords = {Animals, Cryoelectron Microscopy, Freezing, Macromolecular Substances, Proteins, Vitrification}, issn = {2059-7983}, doi = {10.1107/S2059798324005229}, author = {Yadav, Swati and Vinothkumar, Kutti R} } @article {140641, title = {Fission yeast spindle dynamics and chromosome segregation fidelity show distinct thermosensitivity.}, journal = {MicroPubl Biol}, volume = {2024}, year = {2024}, month = {2024}, abstract = {

Cellular processes rely on proteins with temperature-dependent stability and activity. While thermosensitivity in biological networks is well-explored, the effect of temperature on complex mechanochemical assemblies, like the spindle, is rarely studied. We examined fission yeast spindle dynamics and chromosome segregation from 15$^{0}$C to 40$^{0}$C. Our findings reveal that these parameters follow U-shaped temperature-dependent curves but reach their minima at different temperatures. Specifically, spindle dynamics peak around 35$^{0}$C, whereas chromosome segregation defects are minimized at 25$^{0}$C. This suggests a scenario in which mitotic errors are tolerated to expedite rapid cell cycle progression.

}, issn = {2578-9430}, doi = {10.17912/micropub.biology.001048}, author = {Chaba, Zachary and Jain, Ishutesh and Tran, Phong T} } @article {145430, title = {Generating controlled gust perturbations using vortex rings.}, journal = {PLoS One}, volume = {19}, year = {2024}, month = {2024}, pages = {e0305084}, abstract = {

To understand the locomotory mechanisms of flying and swimming animals, it is often necessary to develop assays that enable us to measure their responses to external gust perturbations. Typically, such measurements have been carried out using a variety of gusts which are difficult to control or characterize owing to their inherently turbulent nature. Here, we present a method of generating discrete gusts under controlled laboratory conditions in the form of a vortex rings which are well-characterized and highly controllable. We also provide the theoretical guidelines underlying the design of gust generators for specific applications. As a case study, we tested the efficacy of this method to study the flight response of freely-flying soldier flies Hermetia illucens. The vortex ring based method can be used to generate controlled gusts to study diverse phenomena ranging from a natural flight in insects to the artificial flight of insect-sized drones and micro-aerial vehicles.

}, keywords = {Animals, Diptera, Flight, Animal, Swimming}, issn = {1932-6203}, doi = {10.1371/journal.pone.0305084}, author = {Gupta, Dipendra and Sane, Sanjay P and Arakeri, Jaywant H} } @article {152147, title = {Genetic load.}, journal = {Curr Biol}, volume = {34}, year = {2024}, month = {2024 Dec 16}, pages = {R1216-R1220}, abstract = {

We tend to assume that all genetic variation is good: the higher the variation in a population, the more diverse its gene pool, the more secure its future. Unfortunately, the relationship between genetic variation and survival of a population or a species is more complex. Some genetic variants are advantageous, increasing the survival and reproductive output of an individual, while others may be neutral now (but potentially advantageous in the future), and finally, some genetic variants are disadvantageous. All organisms carry a burden of disadvantageous genetic variants, called {\textquoteright}genetic load{\textquoteright}. This genetic load can lead to diseases or morphological abnormalities and reduce survival or reproduction. Although genetic load has been studied for decades, recent technological advances now enable a more detailed understanding of its characteristics and potential consequences in wild species.

}, keywords = {Animals, Genetic Load, Genetic Variation, Reproduction}, issn = {1879-0445}, doi = {10.1016/j.cub.2024.11.004}, author = {Grossen, Christine and Ramakrishnan, Uma} } @article {142309, title = {A genetic screen to uncover mechanisms underlying lipid transfer protein function at membrane contact sites }, journal = {Life Sci Alliance}, volume = {7}, year = {2024}, month = {03/2024}, pages = {e202302525}, abstract = {

Lipid transfer proteins mediate the transfer of lipids between organelle membranes, and the loss of function of these proteins has been linked to neurodegeneration. However, the mechanism by which loss of lipid transfer activity leads to neurodegeneration is not understood. In Drosophila photoreceptors, depletion of retinal degeneration B (RDGB), a phosphatidylinositol transfer protein, leads to defective phototransduction and retinal degeneration, but the mechanism by which loss of this activity leads to retinal degeneration is not understood. RDGB is localized to membrane contact sites through the interaction of its FFAT motif with the ER integral protein VAP. To identify regulators of RDGB function in vivo, we depleted more than 300 VAP-interacting proteins and identified a set of 52 suppressors of rdgB The molecular identity of these suppressors indicates a role of novel lipids in regulating RDGB function and of transcriptional and ubiquitination processes in mediating retinal degeneration in rdgB9 The human homologs of several of these molecules have been implicated in neurodevelopmental diseases underscoring the importance of VAP-mediated processes in these disorders.

}, doi = {10.26508/lsa.202302525}, author = {Mishra, S. and Manohar, V. and Chandel, S. and Manoj, T. and Bhattacharya, S. and Hegde, N. and Nath, V.R. and Krishnan, H. and Wendling, C. and Mattia, T.D. and Martinet, A. and Chimata, P. and Alpy, F. and Raghu, Padinjat} } @article {149951, title = {Genome-wide association study reveals effect of nsSNPs on candidate genes in rice during iron deficiency.}, journal = {Funct Integr Genomics}, volume = {24}, year = {2024}, month = {2024 Oct 25}, pages = {198}, abstract = {

Resource-poor areas with moisture deficit lands following aerobic and direct seeded rice (DSR) methods of cultivation face severe problems of iron deficiency. In this study, Bengal and Assam Aus rice panel was phenotyped at the seedling stage using an iron-deprived hydroponic medium for various shoot and root traits. A novel iron deficiency scoring scale was used to classify the tolerance reaction and could range anywhere between 0 and 9, indicating the most tolerant and susceptible, respectively. The GWAS results identified four putative candidate genes; OsFLA for number of leaves and shoot length, OsBIDK1 for root traits; average diameter, volume, biomass, projected area, and surface area, OsHPL3 for chlorophyll index of the third leaf and AKR2B (XBOS252) was for Fe score, (which was earlier reported in relation to Xa21). The nsSNP (nsSNPs) variations in these gene sequences were used to group the panel and identify superior haplotypes and donors. BR16 was identified as a superior donor, with higher chlorophyll index and shoot length than RA23, also higher values for root traits like root average diameter, root volume, root projected area and root surface area followed by Shete Bhado. The impact of identified nsSNPs on protein structure and stability was investigated. The conserved domains detected in the mutated proteins of the superior haplotypes are very informative, highlighting that natural selection favors abiotic stress tolerant variants in resource poor areas. Thus, justifying our choice of Aus landraces for association mapping of Fe deficiency tolerant genes in rice.

}, keywords = {Chlorophyll, Genome-Wide Association Study, Iron Deficiencies, Oryza, Plant Proteins, Plant Roots, Polymorphism, Single Nucleotide}, issn = {1438-7948}, doi = {10.1007/s10142-024-01478-w}, author = {Panda, Siddharth and Anandan, Annamalai and Shafi, K Mohamed and Naika, Mahantesha B N and Sowdhamini, R and Vanishree, G and Sarkar, Sutapa and Travis, Anthony J and Norton, Gareth J and Price, Adam H} } @article {142312, title = {A geometrical model of cell fate specification in the mouse blastocyst.}, journal = {Development}, volume = {151}, year = {2024}, month = {2024 Apr 15}, abstract = {

The lineage decision that generates the epiblast and primitive endoderm from the inner cell mass (ICM) is a paradigm for cell fate specification. Recent mathematics has formalized Waddington{\textquoteright}s landscape metaphor and proven that lineage decisions in detailed gene network models must conform to a small list of low-dimensional stereotypic changes called bifurcations. The most plausible bifurcation for the ICM is the so-called heteroclinic flip that we define and elaborate here. Our re-analysis of recent data suggests that there is sufficient cell movement in the ICM so the FGF signal, which drives the lineage decision, can be treated as spatially uniform. We thus extend the bifurcation model for a single cell to the entire ICM by means of a self-consistently defined time-dependent FGF signal. This model is consistent with available data and we propose additional dynamic experiments to test it further. This demonstrates that simplified, quantitative and intuitively transparent descriptions are possible when attention is shifted from specific genes to lineages. The flip bifurcation is a very plausible model for any situation where the embryo needs control over the relative proportions of two fates by a morphogen feedback.

}, keywords = {Animals, Blastocyst, Cell Differentiation, Cell Lineage, Endoderm, Fibroblast Growth Factors, Gene Expression Regulation, Developmental, Germ Layers, Mice, Models, Biological, Signal Transduction}, issn = {1477-9129}, doi = {10.1242/dev.202467}, author = {Raju, Archishman and Siggia, Eric D} } @article {140650, title = {Ghatippuspaschima, a new species and genus of plexippine jumping spider from the Western Ghats of India (Salticidae, Plexippini, Plexippina).}, journal = {Zookeys}, volume = {1191}, year = {2024}, month = {2024}, pages = {89-103}, abstract = {

We propose a new genus of plexippine jumping spiders from the Western Ghats of India based on the new species While it bears a superficial resemblance to in body form and in membrane-bearing embolus, our UCE phylogenomic data-the first to resolve broad relationships within the Plexippina-as well as morphological features justify its status as a new genus. In addition to the molecular data and morphological descriptions, we provide photographs of living specimens of and information on their natural history.

}, issn = {1313-2989}, doi = {10.3897/zookeys.1191.114117}, author = {Marathe, Kiran and Maddison, Wayne P and Kunte, Krushnamegh} } @article {149382, title = {HD-ZIP IV genes are essential for embryo initial cell polarization and the radial axis formation in Arabidopsis.}, journal = {Curr Biol}, year = {2024}, month = {2024 Sep 15}, abstract = {

Plants develop along apical-basal and radial axes. In Arabidopsis thaliana, the radial axis becomes evident when the cells of the 8-cell proembryo divide periclinally, forming inner and outer cell layers. Although changes in cell polarity or morphology likely precede this oriented cell division, the initial events and the factors regulating radial axis formation remain elusive. Here, we report that three transcription factors belonging to the class IV homeodomain-leucine zipper (HD-ZIP IV) family redundantly regulate radial pattern formation: HOMEODOMAIN GLABROUS11 (HDG11), HDG12, and PROTODERMAL FACTOR2 (PDF2). The hdg11 hdg12 pdf2 triple mutant failed to undergo periclinal division at the 8-cell stage and cell differentiation along the radial axis. Live-cell imaging revealed that the mutant defect is already evident in the behavior of the embryo{\textquoteright}s initial cell (apical cell), which is generated by zygote division. In the wild type, the apical cell grows longitudinally and then radially, and its nucleus remains at the bottom of the cell, where the vertical cell plate emerges. By contrast, the mutant apical cell elongates longitudinally, and its nucleus releases from its basal\ position, resulting in a transverse division. Computer simulations based on the live-cell imaging data\ confirmed the importance of the geometric rule (the minimal plane principle and nucleus-passing principle) in determining the cell division plane. We propose that HDG11, HDG12, and PDF2 promote apical cell polarization, i.e., radial cell growth and basal nuclear retention, and set proper radial axis formation during embryogenesis.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2024.08.038}, author = {Tanaka, Sayuri and Matsushita, Yuuki and Hanaki, Yuga and Higaki, Takumi and Kamamoto, Naoya and Matsushita, Katsuyoshi and Higashiyama, Tetsuya and Fujimoto, Koichi and Ueda, Minako} } @article {149376, title = {Heteroplasmy in action: tracking mtDNA segregation dynamics.}, journal = {EMBO J}, year = {2024}, month = {2024 Sep 10}, issn = {1460-2075}, doi = {10.1038/s44318-024-00226-x}, author = {Dua, Nitish and Badrinarayanan, Anjana} } @article {149406, title = {Honoring a Legacy: "Vigyan Ratna" Prof. G. Padmanaban.}, journal = {ACS Infect Dis}, year = {2024}, month = {2024 Oct 03}, issn = {2373-8227}, doi = {10.1021/acsinfecdis.4c00759}, author = {Sundaramurthy, Varadharajan and Haldar, Jayanta} } @article {150950, title = {Identifying memory genes in cancer drug tolerance.}, journal = {Nat Rev Cancer}, year = {2024}, month = {2024 Dec 02}, issn = {1474-1768}, doi = {10.1038/s41568-024-00780-w}, author = {Chakrabarti, Shaon} } @article {140648, title = {IFT88 maintains sensory function by localising signalling proteins along cilia.}, journal = {Life Sci Alliance}, volume = {7}, year = {2024}, month = {2024 May}, abstract = {

Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show r IFT88 (IFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in hearing and negative-gravitaxis behaviour, and a yet uncharacterised Guanylyl Cyclase 2d (Gucy2d/CG34357) as IFT88 cargoes. We also show IFT88 binding to the cyclase{\textasciiacute}s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of Gucy2d. Finally, acute knockdown of both IFT88 and Gucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves IFT88 and at least two of its signalling transmembrane cargoes, Gucy2d and Inactive.

}, keywords = {Animals, Cilia, Drosophila, Drosophila melanogaster, Drosophila Proteins, Hearing}, issn = {2575-1077}, doi = {10.26508/lsa.202302289}, author = {Werner, Sascha and Okenve-Ramos, Pilar and Hehlert, Philip and Zitouni, Sihem and Priya, Pranjali and Mendon{\c c}a, Susana and Sporbert, Anje and Spalthoff, Christian and G{\"o}pfert, Martin C and Jana, Swadhin Chandra and Bettencourt-Dias, M{\'o}nica} } @article {140659, title = {Immunogenicity of SARS-CoV-2 vaccines BBV152 (COVAXIN{\textregistered}) and ChAdOx1 nCoV-19 (COVISHIELD{\texttrademark}) in seronegative and seropositive individuals in India: a multicentre, nonrandomised observational study.}, journal = {Lancet Reg Health Southeast Asia}, volume = {22}, year = {2024}, month = {2024 Mar}, pages = {100361}, abstract = {

BACKGROUND: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May\ 2021.

METHODS: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin{\textregistered} (4 weeks apart) or two doses of Covishield{\texttrademark} (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination.

FINDINGS: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield{\texttrademark} elicited higher antibody responses than Covaxin{\textregistered} as measured by seroconversion rate (98.3\% vs 74.4\%, p\ \<\ 0.0001 in seronegative individuals; 91.7\% vs 66.9\%, p\ \<\ 0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 binding antibody units/ml [BAU/ml], p\ \<\ 0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p\ \<\ 0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield{\texttrademark} recipients than in Covaxin{\textregistered} recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the omicron wave. In seronegative individuals, Covishield{\texttrademark} elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin{\textregistered} elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals.

INTERPRETATION: Covishield{\texttrademark} elicited immune responses of higher magnitude and breadth than Covaxin{\textregistered} in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population.

FUNDING: Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL).

}, issn = {2772-3682}, doi = {10.1016/j.lansea.2024.100361}, author = {Asokan, Mangaiarkarasi S and Joan, Roshni Florina and Babji, Sudhir and Dayma, Girish and Nadukkandy, Prajitha and Subrahmanyam, Vinutha and Pandey, Archana and Malagi, Girish and Arya, Pooja and Mahajan, Vibhuti and Bhavikatti, Jayateerth and Pawar, Ketakee and Thorat, Aishwarya and Shah, Priyanki and Goud, Ramakrishna B and Roy, Bishnudeo and Rajukutty, Shon and Immanuel, Sushil and Agarwal, Dhiraj and Saha, Sankhanil and Shivaraj, Akshatha and Panikulam, Patricia and Shome, Rajeshwari and Gulzar, Shah-E-Jahan and Sharma, Anusmrithi U and Naik, Ajinkya and Talashi, Shruti and Belekar, Madhuri and Yadav, Ritu and Khude, Poornima and V, Mamatha and Shivalingaiah, Sudarshan and Deshmukh, Urmila and Bhise, Chinmayee and Joshi, Manjiri and Inbaraj, Leeberk Raja and Chandrasingh, Sindhulina and Ghose, Aurnab and Jamora, Colin and Karumbati, Anandi S and Sundaramurthy, Varadharajan and Johnson, Avita and Ramesh, Naveen and Chetan, Nirutha and Parthiban, Chaitra and Ahmed, Asma and Rakshit, Srabanti and Adiga, Vasista and D{\textquoteright}Souza, George and Rale, Vinay and George, Carolin Elizabeth and John, Jacob and Kawade, Anand and Chaturvedi, Akanksha and Raghunathan, Anu and Dias, Mary and Bhosale, Anand and Raghu, Padinjat and Shashidhara, L S and Vyakarnam, Annapurna and Bal, Vineeta and Kang, Gagandeep and Mayor, Satyajit} } @article {149411, title = {Immunoproteasome as a biomarker for immunotherapy.}, journal = {Nat Rev Cancer}, year = {2024}, month = {2024 Oct 15}, issn = {1474-1768}, doi = {10.1038/s41568-024-00759-7}, author = {Sabarinathan, Radhakrishnan} } @article {137343, title = {IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium.}, journal = {Life Sci Alliance}, volume = {7}, year = {2024}, month = {12/2023}, pages = {e202302425}, abstract = {

Lithium (Li) is widely used as a mood stabilizer to treat bipolar affective disorder. However, the molecular targets of Li that underpin its therapeutic effect remain unresolved. Inositol monophosphatase (IMPA1) is an enzyme involved in phosphatidylinositol 4,5-bisphosphate (PIP2) resynthesis after PLC signaling. In vitro, Li inhibits IMPA1, but the relevance of this inhibition within neural cells remains unknown. Here, we report that treatment with therapeutic concentrations of Li reduces receptor-activated calcium release from intracellular stores and delays PIP2 resynthesis. These effects of Li are abrogated in IMPA1 deleted cells. We also observed that in human forebrain cortical neurons, treatment with Li reduced neuronal excitability and calcium signals. After Li treatment of human cortical neurons, transcriptome analyses revealed down-regulation of signaling by glutamate, a key excitatory neurotransmitter in the human brain. Collectively, our findings suggest that inhibition of IMPA1 by Li reduces receptor-activated PLC signaling and neuronal excitability.

}, doi = {10.26508/lsa.202302425}, author = {Saha, S and Krishnan, H and Raghu, Padinjat} } @article {145421, title = {Imprinting reversible deformations on a compressed soft rod network}, journal = {SOFT MATTER}, volume = {20}, year = {2024}, month = {06/2024}, abstract = {

We present emergent behaviour of storing mechanical deformation in compressed soft cellular materials (a network of soft polymeric rods). Under an applied compressive strain field, the soft cellular material transits from an elastic regime to a {\textquoteright}pseudo-plastic{\textquoteright} regime (not to be confused with pseudoplasticity in fluids). In the elastic phase, it is capable of forgetting (or relaxing) any applied indentation once the applied indentation is removed. This relaxation will be determined by the visco-elasticity and internal relaxation timescales in polymeric hyperelastic cellular materials. In the pseudo-plastic phase, however, the material is capable of storing local indentation (or deformation) indefinitely. This deformation can be erased via removal of the external strain field and is therefore reversible. We characterise this behaviour experimentally and present a simple model that makes use of friction for understanding this behavior.

We present emergent behaviour of storing mechanical deformation in compressed soft cellular materials (a network of soft polymeric rods).

}, doi = {10.1039/d4sm00099d}, author = {Jain, Harsh and Ghosh, Shankar} } @article {152143, title = {Indian wildlife ecology comes of age.}, journal = {Nat Ecol Evol}, year = {2024}, month = {2024 Dec 16}, issn = {2397-334X}, doi = {10.1038/s41559-024-02622-2}, author = {Bhaumik, Vaishali and Kumar, Ajith and Ratnam, Jayashree} } @article {145432, title = {Insect Flight: State of the Field and Future Directions.}, journal = {Integr Comp Biol}, year = {2024}, month = {2024 Jul 09}, abstract = {

The evolution of flight in an early winged insect ancestral lineage is recognized as a key adaptation explaining the unparalleled success and diversification of insects. Subsequent transitions and modifications to flight machinery, including secondary reductions and losses, also play a central role in shaping the impacts of insects on broadscale geographic and ecological processes and patterns in the present and future. Given the importance of insect flight, there has been a centuries-long history of research and debate on the evolutionary origins and biological mechanisms of flight. Here, we revisit this history from an interdisciplinary perspective, discussing recent discoveries regarding the developmental origins, physiology, biomechanics, and neurobiology and sensory control of flight in a diverse set of insect models. We also identify major outstanding questions yet to be addressed and provide recommendations for overcoming current methodological challenges faced when studying insect flight, which will allow the field to continue to move forward in new and exciting directions. By integrating mechanistic work into ecological and evolutionary contexts, we hope that this synthesis promotes and stimulates new interdisciplinary research efforts necessary to close the many existing gaps about the causes and consequences of insect flight evolution.

}, issn = {1557-7023}, doi = {10.1093/icb/icae106}, author = {Treidel, Lisa A and Deem, Kevin D and Salcedo, Mary K and Dickinson, Michael H and Bruce, Heather S and Darveau, Charles-A and Dickerson, Bradley H and Ellers, Olaf and Glass, Jordan R and Gordon, Caleb M and Harrison, Jon F and Hedrick, Tyson L and Johnson, Meredith G and Lebenzon, Jacqueline E and Marden, James H and Niitep{\~o}ld, Kristjan and Sane, Sanjay P and Sponberg, Simon and Talal, Stav and Williams, Caroline M and Wold, Ethan S} } @article {147301, title = {An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome.}, journal = {Proc Natl Acad Sci U S A}, volume = {121}, year = {2024}, month = {2024 Aug 13}, pages = {e2318601121}, abstract = {

Serial capture affinity purification (SCAP) is a powerful method to isolate a specific protein complex. When combined with cross-linking mass spectrometry and computational approaches, one can build an integrated structural model of the isolated complex. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone reader that recognizes trimethylated histone H3 lysine4 (H3K4me3). In contrast to a previous SCAP analysis of the SPIN1:SPINDOC complex, histones and the H3K4me3 mark were enriched with the WDR76:SPIN1 complex. Next, interaction network analysis of copurifying proteins and microscopy analysis revealed a potential role of the WDR76:SPIN1 complex in the DNA damage response. Since we detected 149 pairs of cross-links between WDR76, SPIN1, and histones, we then built an integrated structural model of the complex where SPIN1 recognized the H3K4me3 epigenetic mark while interacting with WDR76. Finally, we used the powerful Bayesian Integrative Modeling approach as implemented in the Integrative Modeling Platform to build a model of WDR76 and SPIN1 bound to the nucleosome.

}, keywords = {ATPases Associated with Diverse Cellular Activities, Carrier Proteins, Cell Cycle Proteins, DNA Damage, DNA Helicases, Histones, Humans, Models, Molecular, Nucleosomes, Protein Binding}, issn = {1091-6490}, doi = {10.1073/pnas.2318601121}, author = {Liu, Xingyu and Zhang, Ying and Wen, Zhihui and Hao, Yan and Banks, Charles A S and Cesare, Joseph and Bhattacharya, Saikat and Arvindekar, Shreyas and Lange, Jeffrey J and Xie, Yixuan and Garcia, Benjamin A and Slaughter, Brian D and Unruh, Jay R and Viswanath, Shruthi and Florens, Laurence and Workman, Jerry L and Washburn, Michael P} } @article {136530, title = {Interfacial residues in protein-protein complexes are in the eyes of the beholder.}, journal = {Proteins}, year = {2024}, month = {2023 Nov 19}, abstract = {

Interactions between proteins are vital in almost all biological processes. The characterization of protein-protein interactions helps us understand the mechanistic basis of biological processes, thereby enabling the manipulation of proteins for biotechnological and clinical purposes. The interface residues of a protein-protein complex are assumed to have the following two properties: (a) they always interact with a residue of a partner protein, which forms the basis for distance-based interface residue identification methods, and (b) they are solvent-exposed in the isolated form of the protein and become buried in the complex form, which forms the basis for Accessible Surface Area (ASA)-based methods. The study interrogates this popular assumption by recognizing interface residues in protein-protein complexes through these two methods. The results show that a few residues are identified uniquely by each method, and the extent of conservation, propensities, and their contribution to the stability of protein-protein interaction varies substantially between these residues. The case study analyses showed that interface residues, unique to distance, participate in crucial interactions that hold the proteins together, whereas the interface residues unique to the ASA method have a potential role in the recognition, dynamics, and specificity of the complex and can also be a hotspot. Overall, the study recommends applying both distance and ASA methods so that some interface residues missed by either method but crucial to the stability, recognition, dynamics, and function of protein-protein complexes are identified in a complementary manner.

}, issn = {1097-0134}, doi = {10.1002/prot.26628}, author = {Parvathy, Jayadevan and Yazhini, Arangasamy and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan} } @article {152149, title = {Interplay of geometry and mechanics in epithelial wound healing.}, journal = {Phys Rev E}, volume = {110}, year = {2024}, month = {2024 Nov}, pages = {054411}, abstract = {

Wound healing is a complex biological process critical for maintaining an organism{\textquoteright}s structural integrity and tissue repair following an infection or injury. Recent studies have unveiled the mechanisms involving the coordination of biochemical and mechanical responses in the tissue in wound healing. In this article, we focus on the healing property of an epithelial tissue as a material while the effects of biological mechanisms such as cell proliferation, tissue intercalation, cellular migration, cell crawling, and filopodia protrusion is minimal. We present a mathematical framework that predicts the fate of a wounded tissue based on the wound{\textquoteright}s geometrical features and the tissue{\textquoteright}s mechanical properties. Precisely, adapting the vertex model of tissue mechanics, we predict whether a wound of a specific size in an epithelial monolayer characterized by certain levels of actomyosin contractility and cell-cell adhesion will heal (i.e., close), shrink in size, or rupture the tissue further. Moreover, we show how tissue-mediated mechanisms such as purse-string tension at the wound boundary facilitate wound healing. Finally, we validate the predictions of our model by designing an experimental setup that enables us to create wounds of specific sizes in kidney epithelial cells (MDCK) monolayers. Altogether, this work sets up a basis for interpreting the interplay of mechanical and geometrical features of a tissue in the process of wound healing.

}, keywords = {Animals, Biomechanical Phenomena, Dogs, Epithelial Cells, Epithelium, Madin Darby Canine Kidney Cells, Mechanical Phenomena, Models, Biological, Wound Healing}, issn = {2470-0053}, doi = {10.1103/PhysRevE.110.054411}, author = {Babu, Nandhu Krishna and Sreepadmanabh, M and Dutta, Sayantan and Bhattacharjee, Tapomoy} } @article {147303, title = {Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.}, journal = {Redox Biol}, volume = {75}, year = {2024}, month = {2024 Sep}, pages = {103285}, abstract = {

The ability of Mycobacterium tuberculosis (Mtb) to tolerate nitric oxide (NO) and superoxide (O) produced by phagocytes contributes to its success as a human pathogen. Recombination of NO and O generates peroxynitrite (ONOO), a potent oxidant produced inside activated macrophages causing lethality in diverse organisms. While the response of Mtb toward NO and O is well established, how Mtb responds to ONOO remains unclear. Filling this knowledge gap is important to understand the persistence mechanisms of Mtb during infection. We synthesized a series of compounds that generate both NO and O, which should combine to produce ONOO. From this library, we identified CJ067 that permeates Mtb to reliably enhance intracellular ONOO levels. CJ067-exposed Mtb strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates, exhibited dose-dependent, long-lasting oxidative stress and growth inhibition. In contrast, Mycobacterium smegmatis (Msm), a fast-growing, non-pathogenic mycobacterial species, maintained redox balance and growth in response to intracellular ONOO. RNA-sequencing with Mtb revealed that CJ067 induces antioxidant machinery, sulphur metabolism, metal homeostasis, and a 4Fe-4S cluster repair pathway (suf operon). CJ067 impaired the activity of the 4Fe-4S cluster-containing TCA cycle enzyme, aconitase, and diminished bioenergetics of Mtb. Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO in vitro and inducible nitric oxide synthase (iNOS)-dependent growth inhibition during macrophage infection. Thus, Mtb is uniquely sensitive to intracellular ONOO and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB).

}, keywords = {Energy Metabolism, Homeostasis, Humans, Iron-Sulfur Proteins, Macrophages, Mycobacterium smegmatis, Mycobacterium tuberculosis, Nitric Oxide, Oxidation-Reduction, Oxidative Stress, Peroxynitrous Acid, Superoxides, Tuberculosis}, issn = {2213-2317}, doi = {10.1016/j.redox.2024.103285}, author = {Dewan, Arshiya and Jain, Charu and Das, Mayashree and Tripathi, Ashutosh and Sharma, Ajay Kumar and Singh, Harshit and Malhotra, Nitish and Seshasayee, Aswin Sai Narain and Chakrapani, Harinath and Singh, Amit} } @article {140647, title = {IPRs and nSOCE-Tied Together at Two Ends.}, journal = {Contact (Thousand Oaks)}, volume = {7}, year = {2024}, month = {2024 Jan-Dec}, pages = {25152564241231092}, abstract = {

All living organisms need to respond appropriately to changes in the extracellular milieu. Cellular mechanisms that enable such responses evolved in parallel with organismal complexity and intracellular Ca signaling is one such mechanism where extracellular signals received at the cell membrane communicate with endoplasmic reticular stores of Ca, to stimulate appropriate Ca-mediated changes in cellular physiology. The amplitude and dynamics of endoplasmic reticulum (ER)-Ca release in response to extracellular signals determines the nature of the cellular response. An understanding of how ER-Ca channels might regulate cellular Ca signaling in different cell types is lacking. In a recent paper, this question has been addressed in the context of neurons ( Chakraborty et al., 2023) and the implications of these new findings are discussed here.

}, issn = {2515-2564}, doi = {10.1177/25152564241231092}, author = {Hasan, Gaiti} } @article {147286, title = {Localisation and function of key axonemal microtubule inner proteins and dynein docking complex members reveal extensive diversity among vertebrate motile cilia.}, journal = {Development}, volume = {151}, year = {2024}, month = {2024 Jul 15}, abstract = {

Vertebrate motile cilia are classified as (9+2) or (9+0), based on the presence or absence of the central pair apparatus, respectively. Cryogenic electron microscopy analyses of (9+2) cilia have uncovered an elaborate axonemal protein composition. The extent to which these features are conserved in (9+0) cilia remains unclear. CFAP53, a key axonemal filamentous microtubule inner protein (fMIP) and a centriolar satellites component, is essential for motility of (9+0), but not (9+2) cilia. Here, we show that in (9+2) cilia, CFAP53 functions redundantly with a paralogous fMIP, MNS1. MNS1 localises to ciliary axonemes, and combined loss of both proteins in zebrafish and mice caused severe outer dynein arm loss from (9+2) cilia, significantly affecting their motility. Using immunoprecipitation, we demonstrate that, whereas MNS1 can associate with itself and CFAP53, CFAP53 is unable to self-associate. We also show that additional axonemal dynein-interacting proteins, two outer dynein arm docking (ODAD) complex members, show differential localisation between types of motile cilia. Together, our findings clarify how paralogous fMIPs, CFAP53 and MNS1, function in regulating (9+2) versus (9+0) cilia motility, and further emphasise extensive structural diversity among these organelles.

}, keywords = {Animals, Axonemal Dyneins, Axoneme, Cilia, Dyneins, Mice, Microtubule-Associated Proteins, Microtubules, Zebrafish, Zebrafish Proteins}, issn = {1477-9129}, doi = {10.1242/dev.202737}, author = {Lu, Hao and Twan, Wang Kyaw and Ikawa, Yayoi and Khare, Vani and Mukherjee, Ishita and Schou, Kenneth B{\o}dtker and Chua, Kai Xin and Aqasha, Adam and Chakrabarti, Saikat and Hamada, Hiroshi and Roy, Sudipto} } @article {140660, title = {A machine-learning tool to identify bistable states from calcium imaging data.}, journal = {J Physiol}, year = {2024}, month = {2024 Mar 14}, abstract = {

Mapping neuronal activation using calcium imaging in vivo during behavioural tasks has advanced our understanding of nervous system function. In almost all of these studies, calcium imaging is used to infer spike probabilities because action potentials activate voltage-gated calcium channels and increase intracellular calcium levels. However, neurons not only fire action potentials, but also convey information via intrinsic dynamics such as by generating bistable membrane potential states. Although a number of tools for spike inference have been developed and are currently being used, no tool exists for converting calcium imaging signals to maps of cellular state in bistable neurons. Purkinje neurons in the larval zebrafish cerebellum exhibit membrane potential bistability, firing either tonically or in bursts. Several studies have implicated the role of a population code in cerebellar function, with bistability adding an extra layer of complexity to this code. In the present study, we develop a tool, CaMLSort, which uses convolutional recurrent neural networks to classify calcium imaging traces as arising from either tonic or bursting cells. We validate this classifier using a number of different methods and find that it performs well on simulated event rasters as well as real biological data that it had not previously seen. Moreover, we find that CaMLsort generalizes to other bistable neurons, such as dopaminergic neurons in the ventral tegmental area of mice. Thus, this tool offers a new way of analysing calcium imaging data from bistable neurons to understand how they participate in network computation and natural behaviours. KEY POINTS: Calcium imaging, compriising the gold standard of inferring neuronal activity, does not report cellular state in neurons that are bistable, such as Purkinje neurons in the cerebellum of larval zebrafish. We model the relationship between Purkinje neuron electrical activity and its corresponding calcium signal to compile a dataset of state-labelled simulated calcium signals. We apply machine-learning methods to this dataset to develop a tool that can classify the state of a Purkinje neuron using only its calcium signal, which works well on real data even though it was trained only on simulated data. CaMLsort (Calcium imaging and Machine Learning based tool to sort intracellular state) also generalizes well to bistable neurons in a different brain region (ventral tegmental area) in a different model organism (mouse). This tool can facilitate our understanding of how these neurons carry out their functions in a circuit.

}, issn = {1469-7793}, doi = {10.1113/JP284373}, author = {Varma, Aalok and Udupa, Sathvik and Sengupta, Mohini and Ghosh, Prasanta Kumar and Thirumalai, Vatsala} } @article {150949, title = {Mathematical basis and toolchain for hierarchical optimization of biochemical networks.}, journal = {PLoS Comput Biol}, volume = {20}, year = {2024}, month = {2024 Dec 02}, pages = {e1012624}, abstract = {

Biological signalling systems are complex, and efforts to build mechanistic models must confront a huge parameter space, indirect and sparse data, and frequently encounter multiscale and multiphysics phenomena. We present HOSS, a framework for Hierarchical Optimization of Systems Simulations, to address such problems. HOSS operates by breaking down extensive systems models into individual pathway blocks organized in a nested hierarchy. At the first level, dependencies are solely on signalling inputs, and subsequent levels rely only on the preceding ones. We demonstrate that each independent pathway in every level can be efficiently optimized. Once optimized, its parameters are held constant while the pathway serves as input for succeeding levels. We develop an algorithmic approach to identify the necessary nested hierarchies for the application of HOSS in any given biochemical network. Furthermore, we devise two parallelizable variants that generate numerous model instances using stochastic scrambling of parameters during initial and intermediate stages of optimization. Our results indicate that these variants produce superior models and offer an estimate of solution degeneracy. Additionally, we showcase the effectiveness of the optimization methods for both abstracted, event-based simulations and ODE-based models.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1012624}, author = {Viswan, Nisha Ann and Tribut, Alexandre and Gasparyan, Manvel and Radulescu, Ovidiu and Bhalla, Upinder S} } @article {152146, title = {Mitochondrial genetic diversity of pest and vector species, Frankliniella schultzei (Thripidae: Thripinae).}, journal = {Mol Biol Rep}, volume = {52}, year = {2024}, month = {2024 Dec 17}, pages = {55}, abstract = {

BACKGROUND: Frankliniella schultzei (Trybom) is a serious pest and a carrier of tospoviruses in major agricultural crops. This species is a historical and unresolved species complex that contains genetically different cryptic species across the globe.

METHODS AND RESULTS: DNA barcodes were generated from freshly collected specimens of F. schultzei from India and Australia using the sanger sequencing. Seventy-five COI sequences were generated from India and Australia. Moreover, 318 sequences were downloaded (India, Australia, Pakistan, and Africa) from the NCBI GenBank to explore the genetic diversity and phylogeny. The minimum and maximum mean interspecific distance between 393 sequences was found to be 7.97\% and 21.50\%, respectively. Bayesian and Neighbour joining clustering indicated the presence of five putative species within F. schultzei that had sympatry and allopatry. Moreover, 20 haplotypes and 140 polymorphic sites were identified. The African clade is unique; it does not share haplotypes with any other countries, suggesting it may represent the true F. schultzei. Haplotype network analysis showed shallow gene flow and deep genetic variation between the populations. Signatures of recent population history events were measured using Fu{\textquoteright}s Fs test and Tajima{\textquoteright}s D test. Morphometric analysis based on seven characters is also carried out.

CONCLUSION: Phylogeny and genetic distance revealed the presence of five putative species within F. schultzei. On the contrary, morphology does not unequivocally corroborate the phylogenetic results, as morphometric analysis showed overlap among these clades. To resolve F. schultzei species complex, whole genome-based sequencing data are very much necessitated.

}, keywords = {Animals, Australia, Bayes Theorem, DNA Barcoding, Taxonomic, DNA, Mitochondrial, Gene Flow, Genetic Variation, Haplotypes, India, Insect Vectors, Mitochondria, Phylogeny, Thysanoptera}, issn = {1573-4978}, doi = {10.1007/s11033-024-10108-4}, author = {Singha, Devkant and Patidar, Abhishek and Pal, Shash and Tyagi, Kaomud and Kumar, Vikas} } @article {147287, title = {Modeling Ligands into Maps Derived from Electron Cryomicroscopy.}, journal = {J Vis Exp}, year = {2024}, month = {2024 Jul 19}, abstract = {

Deciphering the protein-ligand interactions in a macromolecular complex is crucial for understanding the molecular mechanism, underlying biological processes, and drug development. In recent years, cryogenic sample electron microscopy (cryoEM) has emerged as a powerful technique to determine the structures of macromolecules and to investigate the mode of ligand binding at near-atomic resolution. Identifying and modeling non-protein molecules in cryoEM maps is often challenging due to anisotropic resolution across the molecule of interest and inherent noise in the data. In this article, the readers are introduced to various software and methods currently used for ligand identification, model building, and refinement of atomic coordinates using selected macromolecules. One of the simplest ways to identify the presence of a ligand, as illustrated with the enolase enzyme, is to subtract the two maps obtained with and without the ligand. The extra density of the ligand is likely to stand out in the difference map even at a higher threshold. There are instances, as shown in the case of metabotropic Glutamate receptor mGlu5, when such simple difference maps cannot be generated. The recently introduced method of deriving the Fo-Fc omit map can serve as a tool for validating and demonstrating the presence of the ligand. Finally, using the well-studied β-galactosidase as an example, the effect of resolution on modeling the ligands and solvent molecules in cryoEM maps is analyzed, and an outlook on how cryoEM can be used in drug discovery is presented.

}, keywords = {Cryoelectron Microscopy, Ligands, Models, Molecular}, issn = {1940-087X}, doi = {10.3791/66310}, author = {Jha, Shaileshanand and Bose, Sucharita and Vinothkumar, Kutti R} } @article {150951, title = {The molecular architecture of the desmosomal outer dense plaque by integrative structural modeling.}, journal = {Protein Sci}, volume = {33}, year = {2024}, month = {2024 Dec}, pages = {e5217}, abstract = {

Desmosomes mediate cell-cell adhesion and are prevalent in tissues under mechanical stress. However, their detailed structural characterization is not available. Here, we characterized the molecular architecture of the desmosomal outer dense plaque (ODP) using Bayesian integrative structural modeling via the Integrative Modeling Platform. Starting principally from the structural interpretation of a cryo-electron tomography (cryo-ET) map of the ODP, we integrated information from x-ray crystallography, an immuno-electron microscopy study, biochemical assays, in silico predictions of transmembrane and disordered regions, homology modeling, and stereochemistry information. The integrative structure was validated by information from imaging, tomography, and biochemical studies that were not used in modeling. The ODP resembles a densely packed cylinder with a plakophilin (PKP) layer and a plakoglobin (PG) layer; the desmosomal cadherins and PKP span these two layers. Our integrative approach allowed us to localize disordered regions, such as the N-terminus of PKP and the C-terminus of PG. We refined previous protein-protein interactions between desmosomal proteins and provided possible structural hypotheses for defective cell-cell adhesion in several diseases by mapping disease-related mutations on the structure. Finally, we point to features of the structure that could confer resilience to mechanical stress. Our model provides a basis for generating experimentally verifiable hypotheses on the structure and function of desmosomal proteins in normal and disease states.

}, keywords = {Bayes Theorem, Cryoelectron Microscopy, Crystallography, X-Ray, Desmosomes, gamma Catenin, Humans, Models, Molecular, Plakophilins}, issn = {1469-896X}, doi = {10.1002/pro.5217}, author = {Pasani, Satwik and Menon, Kavya S and Viswanath, Shruthi} } @article {144830, title = {Molecular basis of distinct responses to drought between rice and wheat genotypes}, journal = {Environmental and Experimental Botany}, volume = {221}, year = {2024}, month = {02/2024}, pages = {105734}, abstract = {

The water-intensive cultivation of rice in flooded conditions poses a great challenge to global water resources, particularly in the face of climate change. Wheat requires significantly less water than rice with fairly high yields. A main research question is whether there are any drought adaptive mechanisms in rice similar to those existing in wheat. We report a study, where precise moisture stress was imposed at the vegetative stage using a high-throughput drought simulator phenomics facility. Variability in stress response was captured through untargeted metabolome analysis. In the first experiment, using two rice cultivars with contrasting drought responses (IR64 and Apo) and a wheat cultivar, Weebill, we found distinct variations in regulation of metabolite levels under well-watered or water-limited conditions, both between and within species. Several biosynthetic pathways, including those of polyamines, flavonoids, flavones, and specific metabolites like sphinganine-1-phosphate and anthranilate were enhanced under water-limited conditions. These metabolites were more abundant in wheat than in rice. Among the rice cultivars, Apo had higher abundance of metabolites than IR64. Regulatory patterns governing these metabolic pathways provided basis for stress responses of the tolerant rice cultivar and wheat. A second experiment was conducted to screen rice germplasm lines for acquired tolerance traits contrasting for drought responsiveness. Eight genotypes (four sensitive and four tolerant ones) were selected to validate the candidate metabolites from the first experiment. In the third experiment, an RT-PCR analysis of the key regulatory genes governing the metabolic pathways was conducted, using plant materials from both experiments. The results of this third experiment provided a strong validation for the relevance of these metabolic pathways under stress in rice. We identified promising rice genotypes that exhibited fold change levels of stress resistance metabolites comparable to those of the wheat cultivar Weebill. This study helped identify key candidate metabolites that can be either developed as markers or as elicitors, and genotypes that can be used as trait donor lines for rice improvement.

}, doi = {doi.org/10.1016/j.envexpbot.2024.105734}, author = {Chaitanya, P and Vijayaraghavareddy, P and Lekshmy, S and Spoorthi, N and Math, RGH and Shinde, DD and Struik, PC and Sreeman, S} } @article {148051, title = {Molecular Dialogue During Host Manipulation by the Vascular Wilt Fungus .}, journal = {Annu Rev Phytopathol}, volume = {62}, year = {2024}, month = {2024 Sep}, pages = {97-126}, abstract = {

Vascular wilt fungi are a group of hemibiotrophic phytopathogens that infect diverse crop plants. These pathogens have adapted to thrive in the nutrient-deprived niche of the plant xylem. Identification and functional characterization of effectors and their role in the establishment of compatibility across multiple hosts, suppression of plant defense, host reprogramming, and interaction with surrounding microbes have been studied mainly in model vascular wilt pathogens and . Comparative analysis of genomes from fungal isolates has accelerated our understanding of genome compartmentalization and its role in effector evolution. Also, advances in recent years have shed light on the cross talk of root-infecting fungi across multiple scales from the cellular to the ecosystem level, covering their interaction with the plant microbiome as well as their interkingdom signaling. This review elaborates on our current understanding of the cross talk between vascular wilt fungi and the host plant, which eventually leads to a specialized lifestyle in the xylem. We particularly focus on recent findings in , including multihost associations, and how they have contributed to understanding the biology of fungal adaptation to the xylem. In addition, we discuss emerging research areas and highlight open questions and future challenges.

}, keywords = {Fusarium, Host-Pathogen Interactions, Plant Diseases, Xylem}, issn = {1545-2107}, doi = {10.1146/annurev-phyto-021722-034823}, author = {Srivastava, Vidha and Patra, Kuntal and Pai, Hsuan and Aguilar-Pontes, Maria Victoria and Berasategui, Aileen and Kamble, Avinash and Di Pietro, Antonio and Redkar, Amey} } @article {150948, title = {Monitoring Influenza A (H1N1, H3N2), RSV, and SARS-CoV-2 Using Wastewater-Based Epidemiology: A 2-Year Longitudinal Study in an Indian Megacity Covering Omicron and Post-Omicron Phases.}, journal = {Food Environ Virol}, volume = {17}, year = {2024}, month = {2024 Nov 19}, pages = {3}, abstract = {

The bourgeoning field of wastewater-based epidemiology (WBE) for the surveillance of several respiratory viruses which includes Influenza A, H1N1pdm09, H3N2, respiratory syncytial viruses (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of interest for public health concerns. However, there are few long-term monitoring studies globally. In this study, respiratory viruses were detected and quantified from 11 sewer sheds by utilizing reverse transcription-quantitative polymerase chain reaction analysis in Pune city, India, from Jan 2022 to Dec 2023. The RNA fragments of respiratory viruses were detected in sewage samples before clinical cases were reported, underscoring the potential of WBE for early detection and monitoring within the population. The Spearman correlation of wastewater viral copies was positively and significantly correlated with the clinically positive case of H1N1pdm09 (ρ = 0.55, p = 1.4 {\texttimes} 10), H3N2 (ρ = 0.25, p = 9.9 {\texttimes} 10), and SARS-CoV-2 (ρ = 0.43, p = 4.1 {\texttimes} 10). The impact of public health interventions on the circulation of infectious respiratory diseases showed a significant difference in the viral load during the period when many preventing measures were carried out against the COVID-19 pandemic (restriction phase), compared to the period when no such preventive measures are followed (no-restriction phase) for Influenza A, H1N1pdm09, H3N2, and RSV with p-value \< 0.05, which indicates the influence of health policy implementation in controlling disease spread. The present study provides an effective approach to detecting multiple respiratory viruses from wastewater and provides insights into the epidemiology of respiratory illnesses. The WBE aids in providing information on the spread of pathogens (viruses) in the community, offering a proactive strategy for public health management, allowing for timely interventions and implementing targeted measures to mitigate the spread of these viruses under one health approach.

}, keywords = {Cities, COVID-19, Humans, India, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza, Human, Longitudinal Studies, Respiratory Syncytial Virus Infections, Respiratory Syncytial Viruses, SARS-CoV-2, Sewage, Wastewater, Wastewater-Based Epidemiological Monitoring}, issn = {1867-0342}, doi = {10.1007/s12560-024-09618-y}, author = {Pramanik, Rinka and Nannaware, Kiran and Malik, Vinita and Shah, Priyanki and Sangewar, Poornima and Gogate, Niharika and Shashidhara, L S and Boargaonkar, Radhika and Patil, Dhawal and Kale, Saurabh and Bhalerao, Asim and Jain, Nidhi and Kamble, Sanjay and Dastager, Syed and Dharne, Mahesh} } @article {147298, title = {Mosaic Atoh1 deletion in the chick auditory epithelium reveals a homeostatic mechanism to restore hair cell number.}, journal = {Dev Biol}, volume = {516}, year = {2024}, month = {2024 Jul 27}, pages = {35-46}, abstract = {

The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.

}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2024.07.017}, author = {Singh, Nishant and Kaushik, Raman and Prakash, Anubhav and Singh Saini, Surjit and Garg, Sonal and Adhikary, Adrija and Ladher, Raj K} } @article {140643, title = {The motor apparatus of head movements in the Oleander hawkmoth (Daphnis nerii, Lepidoptera).}, journal = {J Comp Neurol}, volume = {532}, year = {2024}, month = {2024 Jan}, pages = {e25577}, abstract = {

Head movements of insects play a vital role in diverse locomotory behaviors including flying and walking. Because insect eyes move minimally within their sockets, their head movements are essential to reduce visual blur and maintain a stable gaze. As in most vertebrates, gaze stabilization behavior in insects requires the integration of both visual and mechanosensory feedback by the neck motor neurons. Although visual feedback is derived from the optic flow over the retina of their compound eyes, mechanosensory feedback is derived from their organs of balance, similar to the vestibular system in vertebrates. In Diptera, vestibular feedback is derived from the halteres-modified hindwings that evolved into mechanosensory organs-and is integrated with visual feedback to actuate compensatory head movements. However, non-Dipteran insects, including Lepidoptera, lack halteres. In these insects, vestibular feedback is obtained from the antennal Johnston{\textquoteright}s organs but it is not well-understood how it integrates with visual feedback during head movements. Indeed, although head movements are well-studied in flies, the underlying motor apparatus in non-Dipteran taxa has received relatively less attention. As a first step toward understanding compensatory head movements in the Oleander hawkmoth Daphnis nerii, we image the anatomy and architecture of their neck joint sclerites and muscles using X-ray microtomography, and the associated motor neurons using fluorescent dye fills and confocal microscopy. Based on these morphological data, we propose testable hypotheses about the putative function of specific neck muscles during head movements, which can shed light on their role in neck movements and gaze stabilization.

}, keywords = {Animals, Dendritic Spines, Eye, Head Movements, Moths, Nerium}, issn = {1096-9861}, doi = {10.1002/cne.25577}, author = {Prusty, Agnish D and Sane, Sanjay P} } @article {139057, title = {Multisensory integration in insect flight control.}, journal = {Biol Lett}, volume = {20}, year = {2024}, month = {2024 Jan}, pages = {20230565}, keywords = {Animals, Insecta}, issn = {1744-957X}, doi = {10.1098/rsbl.2023.0565}, author = {Sane, Sanjay P and Wehling, Ric and Daniel, Tom} } @article {140651, title = {Mutational signatures in wild type Escherichia coli strains reveal predominance of DNA polymerase errors.}, journal = {Genome Biol Evol}, year = {2024}, month = {2024 Feb 24}, abstract = {

While mutational processes operating in the Escherichia coli genome have been revealed by multiple laboratory experiments, the contribution of these processes to accumulation of bacterial polymorphism and evolution in natural environments is unknown. To address this question, we reconstruct signatures of distinct mutational processes from experimental data on E. coli hypermutators, and ask how these processes contribute to differences between naturally occurring E. coli strains. We show that both mutations accumulated in the course of evolution of wild type strains in nature and in the lab-grown non-mutator laboratory strains are explained predominantly by the low fidelity of DNA polymerases II and III. By contrast, contributions specific to disruption of DNA repair systems cannot be detected, suggesting that temporary accelerations of mutagenesis associated with such disruptions are unimportant for within-species evolution. These observations demonstrate that accumulation of diversity in bacterial strains in nature is predominantly associated with errors of DNA polymerases.

}, issn = {1759-6653}, doi = {10.1093/gbe/evae035}, author = {Garushyants, Sofya K and Sane, Mrudula and Selifanova, Maria V and Agashe, Deepa and Bazykin, Georgii A and Gelfand, Mikhail S} } @article {149370, title = {Neuroepithelial bodies and terminal bronchioles are niches for distinctive club cells that repair the airways following acute notch inhibition.}, journal = {Cell Rep}, volume = {43}, year = {2024}, month = {2024 Sep 24}, pages = {114654}, abstract = {

Lower airway club cells (CCs) serve the dual roles of a secretory cell and a stem cell. Here, we probe how the\ CC fate is regulated. We find that, in response to acute perturbation of Notch signaling, CCs adopt distinct fates. Although the vast majority transdifferentiate into multiciliated cells, a "variant" subpopulation (v-CCs), juxtaposed to neuroepithelial bodies (NEBs; 5\%-10\%) and located at bronchioalveolar duct junctions (\>80\%), does not. Instead, v-CCs transition into lineage-ambiguous states but can revert to a CC fate upon restoration of Notch signaling and repopulate the airways with CCs and multiciliated cells. The v-CC response to Notch inhibition is dependent on localized activation of β-catenin in v-CCs. We propose that the CC fate is stabilized by canonical Notch signaling, that airways are susceptible to perturbations to this pathway, and that NEBs/terminal bronchioles comprise niches that modulate CC plasticity via β-catenin activation to facilitate airway repair post Notch inhibition.

}, keywords = {Animals, beta Catenin, Bronchioles, Mice, Mice, Inbred C57BL, Neuroepithelial Bodies, Receptors, Notch, Signal Transduction}, issn = {2211-1247}, doi = {10.1016/j.celrep.2024.114654}, author = {Lingamallu, Sai Manoz and Deshpande, Aditya and Joy, Neenu and Ganeshan, Kirthana and Ray, Neelanjana and Ladher, Rajesh Kumar and Taketo, Makoto Mark and Lafkas, Daniel and Guha, Arjun} } @article {131933, title = {A new species of Piarosoma Hampson, 1893 (Lepidoptera, Zygaenidae, Procridinae, Artonini) from Arunachal Pradesh, India.}, journal = {Zootaxa}, volume = {5270}, year = {2024}, month = {2023 Apr 19}, pages = {139-145}, abstract = {

A new species, Piarosoma arunachalensis sp. nov., is described and illustrated based on external characters and the genitalia of two male specimens from Tale Wildlife Sanctuary, Lower Subansiri District, Arunachal Pradesh, India. The new species is distinguished from other Piarosoma by a combination of: a) presence of large hyaline patches on the wings, b) the absence of any white or yellow markings on the patagia and the abdominal segments, and c) differences in male genitalia.

}, keywords = {Animals, Animals, Wild, Genitalia, Genitalia, Male, India, Lepidoptera, Male, Moths}, issn = {1175-5334}, doi = {10.11646/zootaxa.5270.1.9}, author = {Sondhi, Sanjay and Efetov, Konstantin A and Tarmann, Gerhard M and Karmakar, Tarun and Pawar, Ujwala and Kunte, Krushnamegh} } @article {139056, title = {A new species of silverline butterfly, Cigaritis Donzel, 1847 (Lepidoptera: Lycaenidae), from the Western Ghats biodiversity hotspot, India.}, journal = {Zootaxa}, volume = {5399}, year = {2024}, month = {2024 Jan 10}, pages = {85-95}, abstract = {

A new species, Cigaritis conjuncta sp. nov. (Lepidoptera: Lycaenidae), is described based on five male and four female specimens from Honey Valley, Kodagu District, Karnataka, which is part of the Western Ghats biodiversity hotspot, India. Cigaritis conjuncta sp. nov. is distinguished from all other congeners in India and Sri Lanka based on the following combination of diagnostic characters in the male: (a) dorsal forewing outer half, costal margin and nearly upper half of the cell black without orange markings, the remaining wing shining deep blue, (b) dorsal hindwing tornus pale orange-red with two black spots, (c) ventral forewing bands at end of discal cell conjoined, and (e) ventral hindwing subbasal and discal bands composed of spots that are not separated but conjoined to form broad bands that have irregular outlines, leaving only a narrow background colour in between. Female is similar on the ventral side, but entirely dark brown above. Male and female genitalia are dissected and figured for two paratypes of each sex, and natural history notes on the species are provided.

}, keywords = {Animals, Biodiversity, Butterflies, Female, India, Lepidoptera, Male}, issn = {1175-5334}, doi = {10.11646/zootaxa.5399.1.7}, author = {Kunte, Krushnamegh and Sengupta, Ashok and Pawar, Ujwala and Nawge, Viraj} } @article {152142, title = {Non-coding genetic variants underlying higher prostate cancer risk in men of African ancestry.}, journal = {Res Sq}, year = {2024}, month = {2024 Dec 05}, abstract = {

Incidence and severity of prostate cancer (PrCa) substantially varies across ancestries. American men of African ancestry (AA) are more likely to be diagnosed with and die from PrCa than the those of European ancestry (EA). Published polygenic risk scores for developing prostate cancer, even those based on multi-ancestry genome-wide association studies, do not address population-specific genetic mechanisms underlying PrCa risk in men of African ancestry. Specifically, the role of non-coding regulatory polymorphisms in driving inter-ancestry variation in PrCa has not been suficiently explored. Here, by employing a sequence-based deep learning model of prostate regulatory enhancers, we identified ~ 2,000 SNPs with higher alternate allele frequency in AA men that potentially affect enhancer function associated with PrCa susceptibility, as supported by our experimental validation. The identified enhancer SNPs (eSNPs) may influence PrCa development through two complementary mechanisms: 1) the alternate allele that increase enhancer activity result in immune suppression and telomere elongation, and 2) the alternate alleles that decrease enhancer activity, lead to de-differentiation and inhibition of apoptosis. Notably, the eSNPs tend to disrupt the binding of known prostate transcription factors including FOX, AR and HOX families. Lastly, the identified eSNPs can be combined into a polygenic risk score that adds value to current GWAS-based risk variants in assessing PrCa risk in independent cohorts.

}, issn = {2693-5015}, doi = {10.21203/rs.3.rs-5485172/v1}, author = {Hannenhalli, Sridhar and Li, Shan and Fatema, Kaniz and Nidharshan, Sundarraj and Singh, Arashdeep and Rajagopal, Padma Sheila and Notani, Dimple and Takeda, David} } @article {144804, title = {Normal Mode Analysis Elicits Conformational Shifts in Proteins at Both Proximal and Distal Regions to the Phosphosite Stemming from Single-Site Phosphorylation.}, journal = {ACS Omega}, volume = {9}, year = {2024}, month = {2024 Jun 11}, pages = {24520-24537}, abstract = {

Phosphorylation, a fundamental biochemical switch, intricately regulates protein function and signaling pathways. Our study employs extensive computational structural analyses on a curated data set of phosphorylated and unphosphorylated protein pairs to explore the multifaceted impact of phosphorylation on protein conformation. Using normal mode analysis (NMA), we investigated changes in protein flexibility post-phosphorylation, highlighting an enhanced level of structural dynamism. Our findings reveal that phosphorylation induces not only local changes at the phosphorylation site but also extensive alterations in distant regions, showcasing its far-reaching influence on protein structure-dynamics. Through in-depth case studies on polyubiquitin B and glycogen synthase kinase-3 beta, we elucidate how phosphorylation at distinct sites leads to variable structural and dynamic modifications, potentially dictating functional outcomes. While phosphorylation largely preserves the residue motion correlation, it significantly disrupts low-frequency global modes, presenting a dualistic impact on protein dynamics. We also explored alterations in the total accessible surface area (ASA), emphasizing region-specific changes around phosphorylation sites. This study sheds light on phosphorylation-induced conformational changes, dynamic modulation, and surface accessibility alterations, leveraging an integrated computational approach with RMSD, NMA, and ASA, thereby contributing to a comprehensive understanding of cellular regulation and suggesting promising avenues for therapeutic interventions.

}, issn = {2470-1343}, doi = {10.1021/acsomega.4c00523}, author = {Subhadarshini, Seemadri and Tandon, Himani and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan} } @article {140662, title = {Optimizing representations for integrative structural modeling using Bayesian model selection.}, journal = {Bioinformatics}, volume = {40}, year = {2024}, month = {2024 Mar 04}, abstract = {

MOTIVATION: Integrative structural modeling combines data from experiments, physical principles, statistics of previous structures, and prior models to obtain structures of macromolecular assemblies that are challenging to characterize experimentally. The choice of model representation is a key decision in integrative modeling, as it dictates the accuracy of scoring, efficiency of sampling, and resolution of analysis. But currently, the choice is usually made ad hoc, manually.

RESULTS: Here, we report NestOR (Nested Sampling for Optimizing Representation), a fully automated, statistically rigorous method based on Bayesian model selection to identify the optimal coarse-grained representation for a given integrative modeling setup. Given an integrative modeling setup, it determines the optimal representations from given candidate representations based on their model evidence and sampling efficiency. The performance of NestOR was evaluated on a benchmark of four macromolecular assemblies.

AVAILABILITY AND IMPLEMENTATION: NestOR is implemented in the Integrative Modeling Platform (https://integrativemodeling.org) and is available at https://github.com/isblab/nestor. Data for the benchmark is at https://www.doi.org/10.5281/zenodo.10360718.

}, keywords = {Bayes Theorem, Benchmarking, Macromolecular Substances}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btae106}, author = {Arvindekar, Shreyas and Pathak, Aditi S and Majila, Kartik and Viswanath, Shruthi} } @article {140644, title = {Orai-mediated calcium entry determines activity of central dopaminergic neurons by regulation of gene expression.}, journal = {Elife}, volume = {12}, year = {2024}, month = {2024 Jan 30}, abstract = {

Maturation and fine-tuning of neural circuits frequently require neuromodulatory signals that set the excitability threshold, neuronal connectivity, and synaptic strength. Here, we present a mechanistic study of how neuromodulator-stimulated intracellular Ca signals, through the store-operated Ca channel Orai, regulate intrinsic neuronal properties by control of developmental gene expression in flight-promoting central dopaminergic neurons (fpDANs). The fpDANs receive cholinergic inputs for release of dopamine at a central brain tripartite synapse that sustains flight (Sharma and Hasan, 2020). Cholinergic inputs act on the muscarinic acetylcholine receptor to stimulate intracellular Ca release through the endoplasmic reticulum (ER) localised inositol 1,4,5-trisphosphate receptor followed by ER-store depletion and Orai-mediated store-operated Ca entry (SOCE). Analysis of gene expression in fpDANs followed by genetic, cellular, and molecular studies identified Orai-mediated Ca entry as a key regulator of excitability in fpDANs during circuit maturation. SOCE activates the transcription factor trithorax-like (Trl), which in turn drives expression of a set of genes, including , that encodes a histone 3 lysine 36 methyltransferase (H3K36me3). Set2 function establishes a positive feedback loop, essential for receiving neuromodulatory cholinergic inputs and sustaining SOCE. Chromatin-modifying activity of Set2 changes the epigenetic status of fpDANs and drives expression of key ion channel and signalling genes that determine fpDAN activity. Loss of activity reduces the axonal arborisation of fpDANs within the MB lobe and prevents dopamine release required for the maintenance of long flight.

}, keywords = {Calcium, Calcium, Dietary, Cholinergic Agents, Dopamine, Dopaminergic Neurons, Histone-Lysine N-Methyltransferase}, issn = {2050-084X}, doi = {10.7554/eLife.88808}, author = {Mitra, Rishav and Richhariya, Shlesha and Hasan, Gaiti} } @article {144782, title = {Phytosynthesis of silver nanoparticles using aqueous sandalwood (Santalum album L.) leaf extract: Divergent effects of SW-AgNPs on proliferating plant and cancer cells.}, journal = {PLoS One}, volume = {19}, year = {2024}, month = {2024}, pages = {e0300115}, abstract = {

The biogenic approach for the synthesis of metal nanoparticles provides an efficient eco-friendly alternative to chemical synthesis. This study presents a novel route for the biosynthesis of silver nanoparticles using aqueous sandalwood (SW) leaf extract as a source of reducing and capping agents under mild, room temperature synthesis conditions. The bioreduction of Ag+ to Ago nanoparticles (SW-AgNPs) was accompanied by the appearance of brown color, with surface plasmon resonance peak at 340-360 nm. SEM, TEM and AFM imaging confirm SW-AgNP{\textquoteright}s spherical shape with size range of 10-32 nm. DLS indicates a hydrodynamic size of 49.53 nm with predominant negative Zeta potential, which can contribute to the stability of the nanoparticles. FTIR analysis indicates involvement of sandalwood leaf derived polyphenols, proteins and lipids in the reduction and capping of SW-AgNPs. XRD determines the face-centered-cubic crystalline structure of SW-AgNPs, which is a key factor affecting biological functions of nanoparticles. This study is novel in using cell culture methodologies to evaluate effects of SW-AgNPs on proliferating cells originating from plants and human cancer. Exposure of groundnut calli cells to SW-AgNPs, resulted in enhanced proliferation leading to over 70\% higher calli biomass over control, enhanced defense enzyme activities, and secretion of metabolites implicated in biotic stress resistance (Crotonyl isothiocyanate, Butyrolactone, 2-Hydroxy-gamma-butyrolactone, Maltol) and plant cell proliferation (dl-Threitol). MTT and NRU were performed to determine the cytotoxicity of nanoparticles on human cervical cancer cells. SW-AgNPs specifically inhibited cervical cell lines SiHa (IC50-2.65 ppm) and CaSki (IC50-9.49 ppm), indicating potential use in cancer treatment. The opposing effect of SW-AgNPs on cell proliferation of plant calli (enhanced cell proliferation) and human cancer cell lines (inhibition) are both beneficial and point to potential safe application of SW-AgNPs in plant cell culture, agriculture and in cancer treatment.

}, keywords = {Cell Line, Tumor, Cell Proliferation, Humans, Metal Nanoparticles, Plant Extracts, Plant Leaves, Santalum, Silver}, issn = {1932-6203}, doi = {10.1371/journal.pone.0300115}, author = {Gowda, Archana and T C, Suman and Anil, Veena S and Raghavan, Swetha} } @article {137345, title = {Plant histone variants at the nexus of chromatin readouts, stress and development.}, journal = {Biochim Biophys Acta Gen Subj}, volume = {1868}, year = {2024}, month = {2023 Dec 10}, pages = {130539}, abstract = {

Histones are crucial proteins that are involved in packaging the DNA as condensed chromatin inside the eukaryotic cell nucleus. Rather than being static packaging units, these molecules undergo drastic variations spatially and temporally to facilitate accessibility of DNA to replication, transcription as well as wide range of gene regulatory machineries. In addition, incorporation of paralogous variants of canonical histones in the chromatin is ascribed to specific functions. Given the peculiar requirement of plants to rapidly modulate gene expression levels on account of their sessile nature, histones and their variants serve as additional layers of gene regulation. This review summarizes the mechanisms and implications of distribution, modifications and differential incorporation of histones and their variants across plant genomes, and outlines emerging themes.

}, issn = {1872-8006}, doi = {10.1016/j.bbagen.2023.130539}, author = {G Vivek Hari Sundar and Madhu, Aravind and Archana, A and Shivaprasad, P V} } @article {152139, title = {Plant-microbe interactions in tropical and subtropical ecosystems.}, journal = {Am J Bot}, volume = {111}, year = {2024}, month = {2024 Dec}, pages = {e16444}, abstract = {

Microbes regulate many dimensions of plant performance with multiscale implications for plant fitness, competition, coexistence, and ecosystem functioning. Yet, this fascinating and diverse arena of study has been limited to a few thematic areas, ecosystems, and regions. In particular, despite growing evidence that microbes may be critical players in the dynamics of plant communities in tropical and subtropical ecosystems, these regions remain poorly represented in studies of plant-microbe interactions. Such geographical gaps limit our ability to draw general inferences to comprehend how microbial effects on plant community dynamics may vary with context and, by extension, respond to global environmental change. In this special section of the American Journal of Botany, we bring together a diverse set of research on plant-microbe interactions from tropical and subtropical ecosystems. These papers explore intraspecific variation of soil microbial communities, the context dependency of host-specific assembly of microbial communities on plants, and the new and exciting frontier of the microbiome of epiphytic plants. We hope that this compilation will fuel deeper forays into the many dimensions of plant-microbe interactions in megadiverse tropical and subtropical forests.

}, keywords = {Ecosystem, Microbiota, Plants, Soil Microbiology, Tropical Climate}, issn = {1537-2197}, doi = {10.1002/ajb2.16444}, author = {Krishnadas, Meghna and Kandlikar, Gaurav and Corrales, Adriana} } @article {145431, title = {Plasticity of the proteasome-targeting signal Fat10 enhances substrate degradation.}, journal = {Elife}, volume = {13}, year = {2024}, month = {2024 Jul 10}, abstract = {

The proteasome controls levels of most cellular proteins, and its activity is regulated under stress, quiescence, and inflammation. However, factors determining the proteasomal degradation rate remain poorly understood. Proteasome substrates are conjugated with small proteins (tags) like ubiquitin and Fat10 to target them to the proteasome. It is unclear if the structural plasticity of proteasome-targeting tags can influence substrate degradation. Fat10 is upregulated during inflammation, and its substrates undergo rapid proteasomal degradation. We report that the degradation rate of Fat10 substrates critically depends on the structural plasticity of Fat10. While the ubiquitin tag is recycled at the proteasome, Fat10 is degraded with the substrate. Our results suggest significantly lower thermodynamic stability and faster mechanical unfolding in Fat10 compared to ubiquitin. Long-range salt bridges are absent in the Fat10 structure, creating a plastic protein with partially unstructured regions suitable for proteasome engagement. Fat10 plasticity destabilizes substrates significantly and creates partially unstructured regions in the substrate to enhance degradation. NMR-relaxation-derived order parameters and temperature dependence of chemical shifts identify the Fat10-induced partially unstructured regions in the substrate, which correlated excellently to Fat10-substrate contacts, suggesting that the tag-substrate collision destabilizes the substrate. These results highlight a strong dependence of proteasomal degradation on the structural plasticity and thermodynamic properties of the proteasome-targeting tags.

}, issn = {2050-084X}, doi = {10.7554/eLife.91122}, author = {Negi, Hitendra and Ravichandran, Aravind and Dasgupta, Pritha and Reddy, Shridivya and Das, Ranabir} } @article {152123, title = {Polychaete worm density correlates with aggregate shorebird density, prey intake rate and foraging success at an intertidal mudflat in Bangladesh}, journal = {ARDEA}, volume = {112}, year = {2024}, month = {02/2024}, abstract = {

Migratory shorebirds have suffered considerable declines because their migratory habits make them susceptible to threats in many different parts of the world. Successful conservation initiatives therefore require an understanding of their ecology not just at their breeding sites, but also at wintering and staging sites. Previous studies have shown that relationships between shorebirds and their wintering habitats are complex and context specific, underlining the importance of continued investigation of their ecology in new contexts. In this study, we investigated the relationship between prey density and shorebird abundance at stretches of mudflat spread across two islands in coastal Bangladesh. To explore whether prey density influenced shorebirds{\textquoteright} ability to find and ingest prey, we also examined relationships with intake rates and foraging success. We found that the density and richness of shorebird communities increased with increasing polychaete worm density across small stretches of mudflat within each island. We also found evidence that prey intake rates and foraging success increased with available food, implying that food as a resource may be limiting in this landscape. Shorebirds may be required to spend more energy foraging in suboptimal habitats, explaining (in part) why densities are higher in habitats with more available prey. Our study suggests that prey density is an important correlate of shorebird density in this important South Asian wintering ground. Our results may have management implications, but this requires further study.

}, doi = {10.5253/arde.2023.a10}, author = {Sultana, Irin and Khandakar, Naim and Das, Delip K. and Quader, Suhel and Viswanathan, Ashwin} } @article {139055, title = {Predictive neural computations in the cerebellum contribute to motor planning and faster behavioral responses in larval zebrafish.}, journal = {Sci Adv}, volume = {10}, year = {2024}, month = {2024 Jan 05}, pages = {eadi6470}, abstract = {

The ability to predict the future based on past experience lies at the core of the brain{\textquoteright}s ability to adapt behavior. However, the neural mechanisms that participate in generating and updating predictions are not clearly understood. Further, the evolutionary antecedents and the prevalence of predictive processing among vertebrates are even less explored. Here, we show evidence of predictive processing via the involvement of cerebellar circuits in larval zebrafish. We presented stereotyped optic flow stimuli to larval zebrafish to evoke swims and discovered that lesioning the cerebellum abolished prediction-dependent modulation of swim latency. When expectations of optic flow direction did not match with reality, error signals arrive at Purkinje cells via the olivary climbing fibers, whereas granule cells and Purkinje cells encode signals of expectation. Strong neural representations of expectation correlate with faster swim responses and vice versa. In sum, our results show evidence for predictive processing in nonmammalian vertebrates with the involvement of cerebellum, an evolutionarily conserved brain structure.

}, keywords = {Animals, Cerebellum, Larva, Neurons, Purkinje Cells, Zebrafish}, issn = {2375-2548}, doi = {10.1126/sciadv.adi6470}, author = {Narayanan, Sriram and Varma, Aalok and Thirumalai, Vatsala} } @article {147283, title = {Ratel Mellivora capensis in a human-dominated savanna landscape in Kachchh, Gujarat, India}, journal = {Small Carnivore Conservation}, volume = {62}, year = {2024}, month = {04/2024}, abstract = {

Between January and May 2022, Ratel Mellivora capensis was recorded at night at five locations during camera-trapping surveys targeting small carnivores in the Kachchh (Kutch) savanna landscape of Gujarat, India. Informal opportunistic conversations with local villagers revealed that they held negative perceptions about the species {\textendash} they opined that it is a large and ferocious animal capable of injuring, or even killing, humans. The fact that the Ratel is rarely seen, together with its depiction in the media as aggressive and indomitable, perhaps shape such perceptions. More in-depth research would be required to understand what influences these misperceptions, how widely held they are locally and how they may be impacting Ratels.

}, url = {https://smallcarnivoreconservation.com/index.php/sccg/article/view/4935}, author = {Ganguly, Divyajyoti and Srivathsa, Arjun} } @article {142318, title = {Reflections on Several Landmark Advances in Circadian Biology.}, journal = {J Circadian Rhythms}, volume = {22}, year = {2024}, month = {2024}, pages = {1}, abstract = {

Circadian Biology intersects with diverse scientific domains, intricately woven into the fabric of organismal physiology and behavior. The rhythmic orchestration of life by the circadian clock serves as a focal point for researchers across disciplines. This retrospective examination delves into several of the scientific milestones that have fundamentally shaped our contemporary understanding of circadian rhythms. From deciphering the complexities of clock genes at a cellular level to exploring the nuances of coupled oscillators in whole organism responses to stimuli. The field has undergone significant evolution lately guided by genetics approaches. Our exploration here considers key moments in the circadian-research landscape, elucidating the trajectory of this discipline with a keen eye on scientific advancements and paradigm shifts.

}, issn = {1740-3391}, doi = {10.5334/jcr.236}, author = {Chawla, Sangeeta and Oster, Henrik and Duffield, Giles E and Maronde, Erik and Guido, Mario E and Chabot, Christopher and Dkhissi-Benyahya, Ouria and Provencio, Ignacio and Goel, Namni and Youngstedt, Shawn D and Zi-Ching Mak, Natalie and Caba, Mario and Nikhat, Anjoom and Chakrabarti, Shaon and Wang, Lei and Davis, Seth J} } @article {145418, title = {Restoration of open ecosystems in the face of climate change}, journal = {GLOBAL ECOLOGY AND CONSERVATION}, volume = {53}, year = {2024}, month = {09/2024}, abstract = {

Open ecosystems occur all around the world in various forms including temperate and tropical grasslands, savannas, shrublands, heathlands, among others. They are home to unique biodiversity, provide key ecosystem services and sustain traditional livelihoods of nearly two billion people. In the face of ongoing climate change, practitioners aiming to restore open ecosystems need the support of the scientific community more than ever. The aim of this Special Issue (SI) is to provide an attention-grabbing collection of high-quality publications addressing the growing challenges of open ecosystems restoration. The SI contains 14 papers that fill various, often interdisciplinary knowledge gaps. Three papers deal with the challenges of identifying the right target states, including the genetic composition of constituting plant species, for restoration under changing environmental conditions and competing stakeholder interests. Five papers advance our understanding on the appropriate timing and methodological toolkit to actively ignite reassembly of the target plant communities, while two papers focus on situations where spontaneous processes can still also be relied on. The interaction of open ecosystems health and recovery with higher trophic levels, particularly grazers, is also discussed in three papers. Finally, a review paper systematically identifies further knowledge gaps, such as the role of soil microbes in grassland recovery and makes clear guidelines how to fill them. Due to the variety of topics and the rigorous content, this SI provides strong support for open ecosystems restoration policy and practice under the UN Decade on Ecosystem Restoration and beyond.

}, doi = {10.1016/j.gecco.2024.e02989}, author = {Tolgyesi, Csaba and Helm, Aveliina and Ratnam, Jayashree and Silveira, FAO and Torok, Peter} } @article {147304, title = {Rigid flocks, undulatory gaits, and chiral foldamers in a chemically active polymer}, journal = {NEW JOURNAL OF PHYSICS}, volume = {26}, year = {2024}, month = {08/2024}, abstract = {

Active matter systems-such as a collection of active colloidal particles-operate far from equilibrium with complex inter-particle interactions that govern their collective dynamics. Predicting the collective dynamics of such systems may aid the design of self-shaping structures comprised of active colloidal units with a prescribed dynamical function. Here, using simulations and theory, we study the collective dynamics of a chain consisting of active Brownian particles with internal interactions via trail-mediated chemicals, connected by harmonic springs in two dimensions to obtain design principles for active colloidal molecules. We show that two-dimensional confinement and chemo-repulsive interactions between the freely-jointed particles lead to an emergent rigidity of the chain in the steady-state dynamics. In the chemo-attractive regime, the chain collapses into crystals that abruptly halt their motion. Further, in a chain consisting of a binary mixture of monomers, we show that non-reciprocal chemical affinities between distinct species give rise to novel phenomena, such as chiral molecules with tunable dynamics, sustained undulatory gaits and reversal of the direction of motion. Our results suggest a novel interpretation of the role of trail-mediated interactions, in addition to providing active self-assembly principles arising due to non-reciprocal interactions.

}, doi = {10.1088/1367-2630/ad6a7c}, author = {Gopal Subramaniam, Arvin and Kumar, Manoj and Thutupalli, Shashi and Singh, Rajesh} } @article {148261, title = {RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.}, journal = {EMBO J}, year = {2024}, month = {2024 Sep 16}, abstract = {

Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.

}, issn = {1460-2075}, doi = {10.1038/s44318-024-00225-y}, author = {Soota, Deepanshu and Saravanan, Bharath and Mann, Rajat and Kharbanda, Tripti and Notani, Dimple} } @article {145429, title = {On the road to losing connectivity: Faecal samples provide genome-wide insights into anthropogenic impacts on two large herbivore species in central India.}, journal = {Mol Ecol}, year = {2024}, month = {2024 Jul 03}, pages = {e17461}, abstract = {

Humans have impacted most of the planet, and the ensuing fragmentation results in small, isolated habitat patches posing a risk of genetic diversity loss, inbreeding, and genetic load. Understanding how natural and anthropogenic landscape features affect gene flow among habitat patches is critical for maintaining connectivity. Genome-wide data are required to comprehend the impacts of recent fragmentation, which can be challenging when only non-invasive samples are available. Here, we build upon advancements in conservation genomics to address connectivity of two large herbivores, gaur (Bos gaurus) and sambar (Rusa unicolor) in central India. Given their habitat associations, we expected these species to respond similarly to habitat fragmentation. We used faecal-DNA and methylation-based host-DNA enrichment with modified ddRAD protocol to generate genome-wide single-nucleotide polymorphism (SNP) data for 124 gaur and 99 sambar individuals. Our findings reveal that gaur populations in central India are fragmented, displaying high genetic differentiation, with drift significantly affecting small populations like Umred Karhandla Wildlife Sanctuary. Although sambar shows low genetic structure, another small population, Bor Tiger Reserve is genetically differentiated. Our results suggest that although land cover change and roads restrict animal movement, the extent of this impact varies across the two species. We show that different species respond differently to landscape features, even with similar habitat associations. We highlight small and isolated populations requiring urgent conservation intervention. Such multi-species approaches enhance our understanding of cross-species connectivity patterns. We suggest shifting from single-species to multi-species holistic conservation approach in rapidly developing landscapes to better manage co-occurring endangered species.

}, issn = {1365-294X}, doi = {10.1111/mec.17461}, author = {Tyagi, Abhinav and Yadav, Nidhi and Pandit, Awadhesh and Ramakrishnan, Uma} } @article {149385, title = {Roles of network topology in the relaxation dynamics of simple chemical reaction network models.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 Sep 27}, pages = {22187}, abstract = {

Understanding the relationship between the structure of chemical reaction networks and their reaction dynamics is essential for unveiling the design principles of living organisms. However, while some network-structural features are known to relate to the steady-state characteristics of chemical reaction networks, mathematical frameworks describing the links between out-of-steady-state dynamics and network structure are still underdeveloped. Here, we characterize the out-of-steady-state behavior of a class of artificial chemical reaction networks consisting of the ligation and splitting reactions of polymers. Within this class, we examine minimal networks that can convert a given set of sources (e.g., nutrients) to a specified set of targets (e.g., biomass precursors). By exploring the dynamics of the models with a simple setup, we find three distinct types of relaxation dynamics after perturbation from a steady-state: exponential-, power-law-, and plateau-dominated. We computationally show that we can predict this out-of-steady-state dynamical behavior from just three features computed from the network{\textquoteright}s stoichiometric matrix, namely, (1) the rank gap, determining the existence of a steady-state; (2) the left null-space, being related to conserved quantities in the dynamics; and (3) the stoichiometric cone, dictating the range of achievable chemical concentrations. We further demonstrate that these three quantities relates to the type of relaxation dynamics of combinations of our minimal networks, larger networks with many redundant pathways, and a real example of a metabolic network. The relationship between the topological features of reaction networks and the relaxation dynamics presented here are useful clues for understanding the design of metabolic reaction networks as well as industrially useful chemical production pathways.

}, issn = {2045-2322}, doi = {10.1038/s41598-024-73104-5}, author = {Himeoka, Yusuke and Kirkegaard, Julius B and Mitarai, Namiko and Krishna, Sandeep} } @article {149952, title = {Seasonal Patterns of Resource Use Within Natural Populations of Burying Beetles.}, journal = {Ecol Evol}, volume = {14}, year = {2024}, month = {2024 Oct}, pages = {e70429}, abstract = {

For organisms in temperate environments, seasonal variation in resource availability and weather conditions exert fluctuating selection pressures on survival and fitness, resulting in diverse adaptive responses. By manipulating resource availability on a local spatial scale, we studied seasonal patterns of resource use within natural populations of burying beetles in a Norfolk woodland. Burying beetles are necrophagous insects that breed on vertebrate carcasses. They are active in Europe between April and October, after which they burrow into the soil and overwinter. Using breeding and chemical analyses, we compared the fecundity and physiological state of beetles that differed in their seasonal resource use. We found seasonal variation in carrion use by wild burying beetles and correlated differences in their reproductive success and cuticular hydrocarbon profiles. Our results provide novel insight into the seasonal correlates of behaviour, physiology and life history in burying beetles.

}, issn = {2045-7758}, doi = {10.1002/ece3.70429}, author = {Issar, Swastika and Leroy, Chlo{\'e} and d{\textquoteright}Ettorre, Patrizia and Kilner, Rebecca M} } @article {149371, title = {Sensing volatiles throughout the body: geographic- and tissue-specific olfactory receptor expression in the fig wasp.}, journal = {Insect Sci}, year = {2024}, month = {2024 Aug 25}, abstract = {

An essential adaptive strategy in insects is the evolution of olfactory receptors (ORs) to recognize important volatile environmental chemical cues. Our model species, Ceratosolen fusciceps, a specialist wasp pollinator of Ficus racemosa, likely possesses an OR repertoire that allows it to distinguish fig-specific volatiles in highly variable environments. Using a newly assembled genome-guided transcriptome, we annotated 63 ORs in the species and reconstructed the phylogeny of Ceratosolen ORs in conjunction with other hymenopteran species. Expression analysis showed that though ORs were mainly expressed in the female antennae, 20\% were also expressed in nonantennal tissues such as the head, thorax, abdomen, legs, wings, and ovipositor. Specific upregulated expression was observed in OR30C in the head and OR60C in the wings. We identified OR expression from all major body parts of female C. fusciceps, suggesting novel roles of ORs throughout the body. Further examination of the OR expression of C. fusciceps in widely separated geographical locations, that is, South (urban) and Northeast (rural) India, revealed distinct OR expression levels in different locations. This discrepancy likely parallels the observed variation in fig volatiles between these regions and provides new insights into the evolution of insect ORs and their expression across geographical locations and tissues.

}, issn = {1744-7917}, doi = {10.1111/1744-7917.13441}, author = {Krishnan, Sushma and Karpe, Snehal Dilip and Kumar, Hithesh and Nongbri, Lucy B and Venkateswaran, Vignesh and Sowdhamini, Ramanathan and Grosse-Wilde, Ewald and Hansson, Bill S and Borges, Renee M} } @article {139053, title = {Shared infection strategy of a fungal pathogen across diverse lineages of land plants, the Fusarium example.}, journal = {Curr Opin Plant Biol}, volume = {77}, year = {2024}, month = {2024 Feb}, pages = {102498}, abstract = {

Plants engage with a wide variety of microorganisms either in parasitic or mutualistic relationships, which have helped them to adapt to terrestrial ecosystems. Microbial interactions have driven plant evolution and led to the emergence of complex interaction outcomes via suppression of host defenses by evolving pathogens. The evolution of plant-microbe interactions is shaped by conserved host and pathogen gene modules and fast-paced lineage-specific adaptability which determines the interaction outcome. Recent findings from different microbes ranging from bacteria, oomycetes, and fungi suggest recurrent concepts in establishing interactions with evolutionarily distant plant hosts, but also clade-specific adaptation that ultimately contributes to pathogenicity. Here, we revisit some of the latest features that illustrate shared colonization strategies of the fungal pathogen Fusarium oxysporum on distant plant lineages and lineage-specific adaptability of mini-chromosomal units encoding effectors, for shaping host-specific pathogenicity in angiosperms.

}, keywords = {Ecosystem, Embryophyta, Fungi, Fusarium, Host-Pathogen Interactions, Plant Diseases, Plants}, issn = {1879-0356}, doi = {10.1016/j.pbi.2023.102498}, author = {Kamble, Avinash and Michavila, Santiago and Gimenez-Ibanez, Selena and Redkar, Amey} } @article {140652, title = {A Simple Immunofluorescence Method to Characterize Neurodegeneration and Tyrosine Hydroxylase Reduction in Whole Brain of a Model of Parkinson{\textquoteright}s Disease.}, journal = {Bio Protoc}, volume = {14}, year = {2024}, month = {2024 Feb 20}, pages = {e4937}, abstract = {

Dopaminergic (DAergic) neurodegeneration in the substantia nigra pars compacta of the human brain is the pathological feature associated with Parkinson{\textquoteright}s disease (PD). also exhibits mobility defects and diminished levels of brain dopamine on exposure to neurotoxicants mimicking PD. Our laboratory demonstrated in a Drosophila model of sporadic PD that there is no decrease in DAergic neuronal number; instead, there is a significant reduction in tyrosine hydroxylase (TH) fluorescence intensity (FI). Here, we present a sensitive assay based on the quantification of FI of the secondary antibody (ab). As the FI is directly proportional to the amount of TH synthesis, its reduction under PD conditions denotes the decrease in the TH synthesis, suggesting DAergic neuronal dysfunction. Therefore, FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using the ZEN 2012 SP2 single-user software; a license must be acquired to utilize the imaging system to interactively control image acquisition, image processing, and analysis. This method will be of good use to biologists, as it can also be used with little modification to characterize the extent of degeneration and changes in the level of degeneration in response to drugs in different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method will be an affordable option for fund-constrained neurobiology laboratories. Key features {\textbullet} Allows characterizing the incipient DAergic and other catecholaminergic neurodegeneration, even in the absence of loss of neuronal cell body. {\textbullet} Great alternative for the fund-constrained neurobiology laboratories in developing countries to utilize this method in different cell types and their response to drugs/nutraceuticals.

}, issn = {2331-8325}, doi = {10.21769/BioProtoc.4937}, author = {Chaurasia, Rahul and Ayajuddin, Mohamad and Ratnaparkhi, Girish S and Lingadahalli, Shashidhara S and Yenisetti, Sarat C} } @article {145412, title = {Spatial patterns in the diet of Gyps vultures in India and their implications for conservation}, journal = {BIOLOGICAL CONSERVATION}, volume = {292}, year = {2024}, month = {04/2024}, abstract = {

Dietary analyses are particularly useful for developing conservation programmes for species threatened by resource depletion, poisoning and environmental pollution. Gyps vultures in South Asia represent one such case, having undergone a population collapse caused by feeding on carcasses of cattle treated with the non-steroidal anti-inflammatory drug diclofenac. Following a ban on the veterinary use of diclofenac, populations of vultures remain low and mostly concentrated near protected areas. Understanding the role of protected areas in the recovery of these critically endangered species requires analyses of spatial variation in their diet. We used faecal metabarcoding to investigate the spatial variation in the diet of Gyps vultures across four landscapes from sites located inside and outside protected areas. We collected faecal 642 samples, of which 419 yielded adequate molecular data to identify the vulture species and 30 molecular operational taxonomic units corresponding to at least 28 diet species. The diet was dominated by large ungulates and varied across landscapes, protection status and vulture species, with the observed variation largely explained by differential intake of wild and domestic species. Domestic livestock was present in \>95 \% of the samples from Central, West and North India, but 77 \% of the samples had only wild species in South India. This variation was explained by livestock density within 100 km radius of the sampling site. Our results imply that protected areas may not offer a respite from possibility of diclofenac-poisoning across most parts of the country and efforts should continue unabated to remove nephrotoxic drugs from veterinary use.

}, doi = {10.1016/j.biocon.2024.110551}, author = {Ghosh-Harihar, Mousumi and Yadav, Nidhi and Gurung, Nehal and Darshan, C. S. and Shashikumar, B. and Vishnudas, C. K. and Prakash, Vibhu and Green, Rhys E. and Ramakrishnan, Uma} } @article {150945, title = {Specialized post-arterial capillaries facilitate adult bone remodelling.}, journal = {Nat Cell Biol}, year = {2024}, month = {2024 Nov 11}, abstract = {

The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts. Endothelial cell-specific overexpression of the transcription factor DACH1 in postnatal mice induces a strong increase in arteries and type R capillaries, leading to local metabolic changes and enabling trabecular bone formation in normally highly hypoxic areas of the diaphysis. Indicating potential clinical relevance of type R capillaries, these vessels respond to anti-osteoporosis treatments and emerge during ageing inside porous structures that are known to weaken compact bone. Our work outlines fundamental principles of vessel specialization in the developing, adult and ageing skeletal system.

}, issn = {1476-4679}, doi = {10.1038/s41556-024-01545-1}, author = {Mohanakrishnan, Vishal and Sivaraj, Kishor K and Jeong, Hyun-Woo and Bovay, Esther and Dharmalingam, Backialakshmi and Bixel, M Gabriele and Dinh, Van Vuong and Petkova, Milena and Paredes Ugarte, Isidora and Kuo, Yi-Tong and Gurusamy, Malarvizhi and Raftrey, Brian and Chu, Nelson Tsz Long and Das, Soumyashree and Rios Coronado, Pamela E and Stehling, Martin and S{\"a}vendahl, Lars and Chagin, Andrei S and M{\"a}kinen, Taija and Red-Horse, Kristy and Adams, Ralf H} } @article {144788, title = {Structural insights into the role of deleterious mutations at the dimeric interface of Toll-like receptor interferon-β related adaptor protein.}, journal = {Proteins}, year = {2024}, month = {2024 May 30}, abstract = {

Toll-like receptors (TLRs) are major players in the innate immune system-recognizing pathogens and differentiating self/non-self components of immunity. These proteins are present either on the plasma membrane or endosome and recognize pathogens at their extracellular domains. They are characterized by a single transmembrane helix and an intracellular toll-interleukin-1 receptor (TIR) domain. Few TIRs directly invoke downstream signaling, while others require other TIR domains of adaptors like TIR domain-containing adaptor-inducing interferon-β (TRIF) and TRIF-related adaptor molecule (TRAM). On recognizing pathogenic lipopolysaccharides, TLR4 dimerises and interacts with the intracellular TRAM dimer through the TIR domain to recruit a downstream signaling adaptor (TRIF). We have performed an in-depth study of the structural effect of two mutations (P116H and C117H) at the dimeric interface of the adaptor TRAM, which are known to abrogate downstream signaling. We modeled the structure and performed molecular dynamics studies in order to decipher the structural basis of this effect. We observed that these mutations led to an increased radius of gyration of the complex and resulted in several changes to the interaction energy values when compared against the wild type (WT) and positive control mutants. We identified highly interacting residues as hubs in the WT dimer, and a few such hubs that were lost in the mutant dimers. Changes in the protein residue path, hampering the information flow between the crucial A86/E87/D88/D89 and T155/S156 sites, were observed for the mutants. Overall, we show that such residue changes can have subtle but long-distance effects, impacting the signaling path allosterically.

}, issn = {1097-0134}, doi = {10.1002/prot.26707}, author = {Verma, Shailya and Menon, Revathy and Sowdhamini, Ramanathan} } @article {144787, title = {Structured and disordered regions of Ataxin-2 contribute differently to the specificity and efficiency of mRNP granule formation}, journal = {PLoS Genetics}, volume = {20}, year = {2024}, month = {05/2024}, pages = {e1011251}, abstract = {

Ataxin-2 (ATXN2) is a gene implicated in spinocerebellar ataxia type II (SCA2), amyotrophic lateral sclerosis (ALS) and Parkinsonism. The encoded protein is a therapeutic target for ALS and related conditions. ATXN2 (or Atx2 in insects) can function in translational activation, translational repression, mRNA stability and in the assembly of mRNP-granules, a process mediated by intrinsically disordered regions (IDRs). Previous work has shown that the LSm (Like-Sm) domain of Atx2, which can help stimulate mRNA translation, antagonizes mRNP-granule assembly. Here we advance these findings through a series of experiments on Drosophila and human Ataxin-2 proteins. Results of Targets of RNA Binding Proteins Identified by Editing (TRIBE), co-localization and immunoprecipitation experiments indicate that a polyA-binding protein (PABP) interacting, PAM2 motif of Ataxin-2 may be a major determinant of the mRNA and protein content of Ataxin-2 mRNP granules. Experiments with transgenic Drosophila indicate that while the Atx2-LSm domain may protect against neurodegeneration, structured PAM2- and unstructured IDR- interactions both support Atx2-induced cytotoxicity. Taken together, the data lead to a proposal for how Ataxin-2 interactions are remodelled during translational control and how structured and non-structured interactions contribute differently to the specificity and efficiency of RNP granule condensation as well as to neurodegeneration.

}, doi = {doi: 10.1371/journal.pgen}, author = {Petrauskas, A. and Fortunati, DL and Kandi, AR and Pothapragada, SS and Agrawal, K. and Singh, A. and Huelsmeier, J. and Hillebrand, J. and Brown, G. and Chaturvedi, D. and Lee, J. and Lim, C. and Auburger, G. and Vijayraghavan, K. and Ramaswami, Mani and Bakthavachalu, Baskar} } @article {152151, title = {Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment.}, journal = {Elife}, volume = {13}, year = {2024}, month = {2024 Dec 27}, abstract = {

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like and . Further, expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with expression. The use of both IL1 Receptor antagonist (IL1RA) and targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (\>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.

}, keywords = {Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Promoter Regions, Genetic, Receptors, Interleukin-1 Type I, Signal Transduction, Telomere, Telomeric Repeat Binding Protein 2, Triple Negative Breast Neoplasms, Tumor Microenvironment}, issn = {2050-084X}, doi = {10.7554/eLife.95106}, author = {Mukherjee, Ananda Kishore and Dutta, Subhajit and Singh, Ankita and Sharma, Shalu and Roy, Shuvra Shekhar and Sengupta, Antara and Chatterjee, Megha and Vinayagamurthy, Soujanya and Bagri, Sulochana and Khanna, Divya and Verma, Meenakshi and Soni, Dristhi and Budharaja, Anshul and Bhisade, Sagar Kailasrao and Anand, Vivek and Perwez, Ahmad and George, Nija and Faruq, Mohammed and Gupta, Ishaan and Sabarinathan, Radhakrishnan and Chowdhury, Shantanu} } @article {149412, title = {Tenkana,, a new genus of jumping spiders (Salticidae, Plexippina) from South Asia, with the new Indian species .}, journal = {Zookeys}, volume = {1215}, year = {2024}, month = {2024}, pages = {91-106}, abstract = {

We describe a new plexippine genus, , supported by phylogenomic data from ultraconserved elements (UCEs), Sanger sequences of four genes, and morphological evidence. The type species, (Caleb, Christudhas, Laltanpuii \& Chitra, 2014), is transferred from , as is (Caleb, 2022), The phylogenomic data places among the plexippines near C.L. Koch, 1846 and Thorell, 1887, while the constrained four-gene phylogeny indicates that is distinct from . Additionally, we describe a new species,

}, issn = {1313-2989}, doi = {10.3897/zookeys.1215.133522}, author = {Marathe, Kiran and Caleb, John T D and Maddison, Wayne P and Nisha, B G and Maliye, Chinmay C and Lohit, Y T and Kunte, Krushnamegh} } @article {145414, title = {The Thermodynamic Properties of Fat10ylated Proteins Are Regulated by the Fat10ylation Site}, journal = {ACS OMEGA}, volume = {9}, year = {2024}, month = {05/2024}, pages = {22265-22276}, abstract = {

Degradation of proteins by the proteasome is crucial in regulating their levels in the cell. Post-translational modifications, such as ubiquitylation and Fat10ylation, trigger proteasomal degradation of the substrate proteins. While ubiquitylation regulates multiple cellular pathways, Fat10ylation functions explicitly in the inflammatory response pathway. At the proteasome, ubiquitin is recycled after being cleaved from the substrate, while Fat10 is degraded simultaneously with its substrate. Although the thermodynamic properties of the substrate are critical for effective proteasomal degradation, they remain poorly understood for the Fat10-proteasome pathway. We studied the thermodynamic properties of the Fat10 similar to substrate conjugate to uncover mechanistic details of the pathway. First, the mechanical unfolding of Fat10 similar to substrate was studied by molecular dynamics simulations, which suggested that the unfolding pathway and unfolding energy of the substrate depend on the site of Fat10 modification. We also investigated different pathways for the entry of the Fat10 similar to substrate into the proteasome core. Our analysis supports a model where the entry of Fat10, followed by the substrate, is the energetically preferred pathway. Further, we studied Fat10{\textquoteright}s effect on the thermodynamic properties of distinct substrates, considering their size, flexibility, and surface properties. The results uncovered significant entropic destabilization of substrates due to Fat10ylation, particularly in smaller substrates. For larger substrates, multi-monoFat10ylation is necessary to induce destabilization. Our study further reveals that Fat10 modification at negative patches on substrate surfaces is essential for optimal destabilization and subsequent degradation. These findings provide atomistic insights into the degradation mechanisms in the Fat10 proteasome pathway with potential implications for therapeutic interventions.

}, doi = {10.1021/acsomega.4c01396}, author = {Ravichandran, Aravind and Das, Ranabir} } @article {152140, title = {Time memory in social insects with a special focus on honey bees.}, journal = {Curr Opin Insect Sci}, volume = {68}, year = {2024}, month = {2024 Dec 13}, pages = {101327}, abstract = {

The ability to associate time and location with food sources is an evolutionary advantage for foraging animals. We find highly sophisticated time memory capabilities especially in social insects, which require efficient foraging capabilities for colony provisioning. Honey bees are perfectly suitable to study time memory mechanisms: they possess an elaborated time memory combined with a relatively simple neuronal clock network and a smaller gene set compared with the mouse model organism. This review provides a short overview majorly across insects, which have demonstrated time memory capabilities, with a focus on time-place learning, and describes basic properties as well as state-of-the-art research connecting time memory with the circadian clock at the behavioral, molecular, and neuroanatomical levels. Despite a long history of research on time memory of honey bees, putative connections between clock and time memory have only recently been identified and imply a rather complex regulation mechanism with multiple signaling pathways.

}, issn = {2214-5753}, doi = {10.1016/j.cois.2024.101327}, author = {Roy, Tiyasa and Beer, Katharina} } @article {142316, title = {Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.}, journal = {J Circadian Rhythms}, volume = {22}, year = {2024}, month = {2024}, pages = {2}, abstract = {

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

}, issn = {1740-3391}, doi = {10.5334/jcr.237}, author = {Chawla, Sangeeta and O{\textquoteright}Neill, John and Knight, Marina I and He, Yuqing and Wang, Lei and Maronde, Erik and Rodr{\'\i}guez, Sergio Gil and van Ooijen, Gerben and Garbarino-Pico, Eduardo and Wolf, Eva and Dkhissi-Benyahya, Ouria and Nikhat, Anjoom and Chakrabarti, Shaon and Youngstedt, Shawn D and Zi-Ching Mak, Natalie and Provencio, Ignacio and Oster, Henrik and Goel, Namni and Caba, Mario and Oosthuizen, Maria and Duffield, Giles E and Chabot, Christopher and Davis, Seth J} } @article {153395, title = {Toll-like receptor 4 pathway evolutionary trajectory and functional emergence.}, journal = {Frontiers in Immunology}, volume = {15}, year = {2024}, month = {2024}, pages = {1494017}, abstract = {

INTRODUCTION: Toll-like receptors 4 (TLR4) recognize lipopolysaccharides (LPS) from bacteria as their conventional ligands and undergo downstream signaling to produce cytokines. They mediate the signaling either by the TIRAP-MyD88 complex or by the TRAM-TRIF complex. The MyD88 pathway is common to all other TLRs, whereas the TRAM-TRIF complex is largely exclusive to TLR4. Here we study the TIR domain of TRAM and TRIF ortholog proteins that are crucial for downstream signaling. Our previous work on pan-genome-wide survey, indicates to be the ancestral organism with both TRAM and TRIF proteins.

METHODS: To gain a deeper insight into the protein function and to compare them with adaptor proteins, we modeled the docking of the TRAM-TRIF complex of representative organisms across various taxa. These modeling experiments provide insights to ascertain a possible interaction surface and calculate the energetics and electrostatic potential of the complex. Furthermore, this enables us to employ normal mode analysis (NMA) to examine fluctuating, interacting, and other specific residue clusters that could have a role in protein functioning in both and . We also performed molecular dynamics simulations of these complexes and cross-validated the functionally important residues using network parameters.

RESULTS: We compared the stoichiometry of TRAM-TRIF complexes and found that the tetrameric models (TRAM and TRIF dimer) were more stable than the trimeric model (TRAM dimer and TRIF monomer). While the critical residues of TIRAP, TRIF, and MyD88 were preserved, we also found that the important residues of TRAM signaling were not conserved in .

DISCUSSION: This suggests the presence of functional TIRAP-MyD88-mediated TLR4 signaling and TRIF-mediated TLR3 signaling in the ancestral species. The overall biological function of this signaling domain appears to be gradually acquired through the orchestration of several motifs through an evolutionary scale.

}, keywords = {Adaptor Proteins, Vesicular Transport, Animals, Evolution, Molecular, Humans, Membrane Glycoproteins, Molecular Docking Simulation, Myeloid Differentiation Factor 88, Protein Binding, Receptors, Interleukin-1, Signal Transduction, Toll-Like Receptor 4}, issn = {1664-3224}, doi = {10.3389/fimmu.2024.1494017}, url = {https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1494017/full}, author = {Verma, Shailya and Sowdhamini, Ramanathan} } @article {149387, title = {Transcriptional regulation of hormone signalling genes in black pepper in response to Phytophthora capsici.}, journal = {BMC Genomics}, volume = {25}, year = {2024}, month = {2024 Sep 30}, pages = {910}, abstract = {

INTRODUCTION: Black pepper (Piper nigrum L.) is a non-model spice crop of significant agricultural and biological importance. The {\textquoteright}quick wilt{\textquoteright} disease caused by the oomycete Phytophthora capsici is a major threat, leading to substantial crop loss. The molecular mechanisms governing the plant immune responses to this pathogen remain unclear. This study employs RNA sequencing and transcriptome analysis to explore the defense mechanisms of P. nigrum against P. capsici.

RESULTS: Two-month-old P. nigrum plantlets were subjected to infection with P. capsici, and leaf samples were collected at 6- and 12-hours post-inoculation. RNA was extracted, sequenced, and the resulting data were processed and assembled. Differential gene expression analysis was conducted to identify genes responding to the infection. Additionally, the study investigated the involvement of Salicylic acid (SA), Jasmonic acid (JA), and Ethylene (ET) signalling pathways. Our transcriptome assembly comprised 64,667 transcripts with 96.7\% completeness, providing valuable insights into the P. nigrum transcriptome. Annotation of these transcripts identified functional categories and domains, provided details on molecular processes. Gene expression analysis identified 4,714 transcripts at 6\ h post-infection (hpi) and 9,416 at 12 hpi as differentially expressed, revealing dynamic regulation of immune-related genes. Furthermore, the study investigated key genes involved in biosynthesis pathways of Salicylic acid, Jasmonic acid, and Ethylene signalling. Notably, we found differential regulation of critical genes associated with these pathways while comparing data before and after infection, thereby shedding light on their roles in defense mechanism in P. nigrum defense.

CONCLUSIONS: This comprehensive transcriptome analysis of P. nigrum response to P. capsici attack provides valuable insights into the plant defense mechanisms. The dynamic regulation of innate immunity and the involvement of key signalling pathways highlight the complexity of the plant-pathogen interaction. This study contributes to our understanding of plant immunity and offers potential strategies for enhancing P. nigrum resistance to this harmful pathogen.

}, keywords = {Cyclopentanes, Disease Resistance, Gene Expression Profiling, Gene Expression Regulation, Plant, Oxylipins, Phytophthora, Piper nigrum, Plant Diseases, Plant Growth Regulators, Signal Transduction, Transcriptome}, issn = {1471-2164}, doi = {10.1186/s12864-024-10802-4}, author = {Mahadevan, Chidambareswaren and Shafi, K Mohamed and Nagarathnam, B and Sakuntala, Manjula and Sowdhamini, Ramanathan} } @article {144794, title = {Tropical and montane Apis cerana show distinct dance-distance calibration curves.}, journal = {J Exp Biol}, year = {2024}, month = {2024 Jun 10}, abstract = {

Social bees have evolved sophisticated communication systems to recruit nestmates to newly found food sources. As foraging ranges can vary from a few hundred meters to several kilometers depending on the environment or season, populations of social bee species living in different climate zones likely show specific adaptations in their recruitment communication. Accordingly, studies in the western honey bee, Apis mellifera, demonstrated that temperate populations exhibit shallower dance-calibration curves compared to tropical populations. Here we report the first comparison of calibration curves for three Indian A. cerana lineages: the tropical A. indica, and the two montane Himalayan populations A. c. cerana (Himachal Pradesh) and A. c. kashmirensis (Jammu and Kashmir). We found that the colonies of the two montane A. cerana populations show dance-distance calibration curves with significantly shallower slopes than the tropical A. indica. Next, we transferred A. c. cerana colonies to Bangalore (\~{} 2600 km away) to obtain calibration curves in the same location as A. indica. The common garden experiment confirmed this difference in slopes, implying that the lineages exhibit genetically fixed differences in dance-distance coding. However, the slopes of the calibration curves of the transferred A. c. cerana colonies were also significantly higher than those tested in Himachal Pradesh indicating an important effect of the environment. The differences in dance-distance coding between temperate and tropical A. cerana lineages resemble those described for A. mellifera suggesting that populatiInons of both species independently evolved similar adaptations.

}, issn = {1477-9145}, doi = {10.1242/jeb.247510}, author = {A K, Bharath Kumar and George, Ebi Antony and Brockmann, Axel} } @article {152136, title = {Two new taxa of brush-footed butterflies (Lepidoptera: Nymphalidae) from the Western Ghats biodiversity hotspot, southern India.}, journal = {Zootaxa}, volume = {5543}, year = {2024}, month = {2024 Dec 04}, pages = {343-367}, abstract = {

A new species, Amathusia travancorica sp. nov. (Nymphalidae: Satyrinae: Amathusiini), and a new subspecies, Athyma inara sahyadriensis ssp. nov. (Nymphalidae: Limenitidinae: Limenitidini), are described from the Western Ghats biodiversity hotspot, India, based on multiple male and female specimens. The new taxa are compared with type specimens of related species and subspecies, revealing consistent differences that distinguish the new taxa. Genitalia dissections are also provided as comparative materials. Additional information is provided on historical records, distributional ranges, habits and habitat, phenology, larval host plants, and early stages. Finally, the type locality and synonymy of Pantoporia mera Swinhoe, 1917 are discussed based on comparison of type specimens (Pantoporia mera Swinhoe, 1917 syn. nov.=Athyma inara Westwood, 1850).

}, keywords = {Animal Distribution, Animal Structures, Animals, Biodiversity, Body Size, Butterflies, Ecosystem, Female, India, Larva, Male, Organ Size}, issn = {1175-5334}, doi = {10.11646/zootaxa.5543.3.3}, author = {Kunte, Krushnamegh and Basu, Dipendra Nath} } @article {137340, title = {The ubiquitous nanocluster: A molecular scale organizing principle that governs cellular information flow.}, journal = {Curr Opin Cell Biol}, volume = {86}, year = {2024}, month = {2023 Dec 05}, pages = {102285}, abstract = {

The language of biology at the scale of the cell is constituted of alphabets represented by biomolecules. These are stitched together in a variety of ways to create meaning. We argue that the phrases of this language are nanoscale molecular assemblies or nano-hubs for the purpose of information flow. At the cell surface information is sensed and processed via membrane receptors, often configured as multimers. These nano-assemblies serve as receiver nano-hubs, which are flexibly configured with additional nano-hubs that we term modifiers and transducers. This framework serves to process information that is transmitted for execution inside the cell. Here, we explore some examples about how nano-hubs are built and how they may contribute to cellular information flow.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2023.102285}, author = {Garcia-Parajo, Maria F and Mayor, Satyajit} } @article {145426, title = {UBR7 in concert with EZH2 inhibits the TGF-β signaling leading to extracellular matrix remodeling.}, journal = {Cell Rep}, volume = {43}, year = {2024}, month = {2024 Jun 25}, pages = {114394}, abstract = {

The intricate interplay between resident cells and the extracellular matrix (ECM) profoundly influences cancer progression. In triple-negative breast cancer (TNBC), ECM architecture evolves due to the enrichment of lysyl oxidase, fibronectin, and collagen, promoting distant metastasis. Here we uncover a pivotal transcription regulatory mechanism involving the epigenetic regulator UBR7 and histone methyltransferase EZH2 in regulating transforming growth factor (TGF)-β/Smad signaling, affecting the expression of ECM genes. UBR7 loss leads to a dramatic reduction in facultative heterochromatin mark H3K27me3, activating ECM genes. UBR7 plays a crucial role in matrix deposition in adherent cancer cells and spheroids, altering collagen content and lysyl oxidase activity, directly affecting matrix stiffness and invasiveness. These findings are further validated in\ vivo in mice models and TNBC patients, where reduced UBR7 levels are accompanied by increased ECM component expression and activity, leading to fibrosis-mediated matrix stiffness. Thus, UBR7 is a master regulator of matrix stiffening, influencing the metastatic potential of TNBC.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2024.114394}, author = {Adhikari, Swagata and Singh, Vipin and Nandi, Sandhik and Ghosal, Manorama and Raj, Nidharshan Sundar and Khanna, Jayati and Bhattacharya, Apoorva and Kabiraj, Aindrila and Mondal, Atanu and Vasudevan, Madavan and Senapati, Dulal and Roy, Himansu and Sengupta, Kundan and Notani, Dimple and Das, Chandrima} } @article {149377, title = {Unraveling the genomic diversity and admixture history of captive tigers in the United States.}, journal = {Proc Natl Acad Sci U S A}, volume = {121}, year = {2024}, month = {2024 Sep 24}, pages = {e2402924121}, abstract = {

Genomic studies of endangered species have primarily focused on describing diversity patterns and resolving phylogenetic relationships, with the overarching goal of informing conservation efforts. However, few studies have investigated genomic diversity housed in captive populations. For tigers (), captive individuals vastly outnumber those in the wild, but their diversity remains largely unexplored. Privately owned captive tiger populations have remained an enigma in the conservation community, with some believing that these individuals are severely inbred, while others believe they may be a source of now-extinct diversity. Here, we present a large-scale genetic study of the private (non-zoo) captive tiger population in the United States, also known as "Generic" tigers. We find that the Generic tiger population has an admixture fingerprint comprising all six extant wild tiger subspecies. Of the 138 Generic individuals sequenced for the purpose of this study, no individual had ancestry from only one subspecies. We show that the Generic tiger population has a comparable amount of genetic diversity relative to most wild subspecies, few private variants, and fewer deleterious mutations. We observe inbreeding coefficients similar to wild populations, although there are some individuals within both the Generic and wild populations that are substantially inbred. Additionally, we develop a reference panel for tigers that can be used with imputation to accurately distinguish individuals and assign ancestry with ultralow coverage (0.25{\texttimes}) data. By providing a cost-effective alternative to whole-genome sequencing (WGS), the reference panel provides a resource to assist in tiger conservation efforts for both ex- and in situ populations.

}, keywords = {Animals, Animals, Zoo, Conservation of Natural Resources, Endangered Species, Genetic Variation, Genome, Genomics, Phylogeny, Tigers, United States}, issn = {1091-6490}, doi = {10.1073/pnas.2402924121}, author = {Armstrong, Ellie E and Mooney, Jazlyn A and Solari, Katherine A and Kim, Bernard Y and Barsh, Gregory S and Grant, Victoria B and Greenbaum, Gili and Kaelin, Christopher B and Panchenko, Katya and Pickrell, Joseph K and Rosenberg, Noah and Ryder, Oliver A and Yokoyama, Tsuya and Ramakrishnan, Uma and Petrov, Dmitri A and Hadly, Elizabeth A} } @article {149375, title = {Upstream regulator of genomic imprinting in rice endosperm is a small RNA-associated chromatin remodeler.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Sep 06}, pages = {7807}, abstract = {

Genomic imprinting is observed in endosperm, a placenta-like seed tissue, where transposable elements (TEs) and repeat-derived small RNAs (sRNAs) mediate epigenetic changes in plants. In imprinting, uniparental gene expression arises due to parent-specific epigenetic marks on one allele but not on the other. The importance of sRNAs and their regulation in endosperm development or in imprinting is poorly understood in crops. Here we show that a previously uncharacterized CLASSY (CLSY)-family chromatin remodeler named OsCLSY3 is essential for rice endosperm development and imprinting, acting as an upstream player in the sRNA pathway. Comparative transcriptome and genetic analysis indicated its endosperm-preferred expression and its likely paternal imprinted nature. These important features are modulated by RNA-directed DNA methylation (RdDM) of tandemly arranged TEs in its promoter. Upon perturbation of OsCLSY3 in transgenic lines, we observe defects in endosperm development and a loss of around 70\% of all sRNAs. Interestingly, well-conserved endosperm-specific sRNAs (siren) that are vital for reproductive fitness in angiosperms are also\ dependent on OsCLSY3. We observed that many imprinted genes and seed development-associated genes are\ under the control of OsCLSY3. These results support an essential role of OsCLSY3 in rice endosperm development and imprinting, and propose similar regulatory strategies involving CLSY3 homologs among other cereals.

}, keywords = {Chromatin Assembly and Disassembly, DNA Methylation, DNA Transposable Elements, Endosperm, Gene Expression Regulation, Plant, Genomic Imprinting, Oryza, Plant Proteins, Plants, Genetically Modified, RNA, Plant, RNA, Small Untranslated}, issn = {2041-1723}, doi = {10.1038/s41467-024-52239-z}, author = {Pal, Avik Kumar and Gandhivel, Vivek Hari-Sundar and Nambiar, Amruta B and Shivaprasad, P V} } @article {149410, title = {Wastewater surveillance in post-omicron silent phase uncovers silent waves and cryptic transmission of SARS-CoV-2 variants; a yearlong study in Western India.}, journal = {Sci Total Environ}, volume = {955}, year = {2024}, month = {2024 Oct 11}, pages = {176833}, abstract = {

Due to reduced clinical testing and evolving monitoring challenges, tracking the emergence and evolution of SARS-CoV-2 variants has become increasingly complex. To address this gap, we investigated the utility of wastewater-based epidemiology (WBE) as a complementary tool for SARS-CoV-2 variant surveillance in sewage treatment plants (STPs) across Pune, India. We analyzed 1128 wastewater samples collected between May 2022 and May 2023, using Illumina and nanopore sequencing techniques for robust detection and variant characterization. The study revealed critical findings, including "silent waves" with elevated viral load despite minimal clinical cases, suggesting potential cryptic transmission. These silent waves aligned with the dominance of Omicron BA.2 in June-July 2022 and emergence of the recombinant XBB clade in December 2022. Importantly, sequencing detected XBB lineages 130-253\ days before their initial clinical identification, demonstrating its significant advantage in early variant detection. Furthermore, wastewater analysis revealed a higher degree of lineage diversity compared to clinical data, indicating its ability to capture a broader spectrum of circulating variants. The BA.2.86.X was identified 103\ days prior to its clinical detection in Pune, highlighting WBE{\textquoteright}s remarkable lead time. Surprisingly, BF.7.X and BQ.X fragments were also detected in wastewater but not yet reported clinically. These findings demonstrate the remarkable value of WBE as an early warning tool for SARS-CoV-2 variants ahead of time. By revealing silent waves, enabling early variant detection, and capturing a broader viral spectrum, WBE effort could empower public health officials to make informed decisions and implement effective strategies to mitigate future waves, especially in contexts with declining clinical testing.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2024.176833}, author = {Rajput, Vinay and Pramanik, Rinka and Nannaware, Kiran and Malik, Vinita and Matra, Sejal and Kumar, Shubham and Joshi, Sai and Kadam, Pradnya and Bhalerao, Unnati and Tupekar, Manisha and Deshpande, Dipti and Shah, Priyanki and Sangewar, Poornima and Gogate, Niharika and Boargaonkar, Radhika and Patil, Dhawal and Kale, Saurabh and Bhalerao, Asim and Jain, Nidhi and Shashidhara, L S and Kamble, Sanjay and Dastager, Syed and Karmodiya, Krishanpal and Dharne, Mahesh} } @article {140655, title = {Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.}, journal = {PLoS Biol}, volume = {22}, year = {2024}, month = {2024 Mar 11}, pages = {e3002540}, abstract = {

DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response in Caulobacter. This response operates independently of the SOS response, governs the expression of genes crucial for direct repair, and is essential for surviving methylation-induced damage. Our molecular investigation of Cada2 reveals a cysteine methylation-dependent posttranslational modification (PTM) and mode of action distinct from its Escherichia coli counterpart, a trait conserved across all bacteria harboring a Cada2-like homolog instead. Extending across the bacterial kingdom, our findings support the notion of divergence and coevolution of adaptive response transcription factors and their corresponding sequence-specific DNA motifs. Despite this diversity, the ubiquitous prevalence of adaptive response regulators underscores the significance of a transcriptional switch, mediated by methylation PTM, in driving a specific and essential bacterial DNA damage response.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3002540}, author = {Kamat, Aditya and Tran, Ngat T and Sharda, Mohak and Sontakke, Neha and Le, Tung B K and Badrinarayanan, Anjana} } @article {140646, title = {William L. Mock and Cucurbituril: The Resurrection of the Behrend Paper of 1905.}, journal = {ACS Omega}, volume = {9}, year = {2024}, month = {2024 Jan 30}, pages = {4162-4165}, abstract = {

In 1905, Robert Behrend reported the preparation of a substance that remained a dry powder despite absorbing water and that had the ability to absorb dyes from solution. Over seven decades later, William L. Mock repeated the Behrend synthesis and discovered cucurbituril, a remarkably symmetric molecule with a central cavity welcoming diverse guests. Mock et al. ploughed a lonely furrow in the 1980s, establishing the versatility of cucurbituril in the field of supramolecular chemistry, including a demonstration of the Huisgen click reaction in a molecular cavity.

}, issn = {2470-1343}, doi = {10.1021/acsomega.3c07196}, author = {Balaram, Padmanabhan} } @article {149373, title = {Wisdom of (molecular) crowds: How a snake{\textquoteright}s temperaturesensing superpower separates information from misinformation.}, journal = {J Biosci}, volume = {49}, year = {2024}, month = {2024}, abstract = {

The namesake pit organ of pit vipers and other temperature-sensing snakes is a remarkable biological thermometer, one that converts infrared light into an electrical signal (Bullock and Diecke 1956). The organ is arranged like a pinhole camera, with a small outward-facing opening covering a pit membrane dense with neuronal projections. This geometry ensures that only light from a narrow angular cone lands on the membrane. By reorienting its head to scan its surroundings, the snake can precisely detect and localise warm-blooded prey even in complete darkness.

}, keywords = {Animals, Snakes, Temperature, Thermosensing}, issn = {0973-7138}, author = {Thattai, Mukund} } @article {147285, title = {Wound-induced small-peptide-mediated signaling cascade, regulated by OsPSKR, dictates balance between growth and defense in rice.}, journal = {Cell Rep}, volume = {43}, year = {2024}, month = {2024 Jul 23}, pages = {114515}, abstract = {

Wounding is a general stress in plants that results from various pest and pathogenic infections in addition to environment-induced mechanical damages. Plants have sophisticated molecular mechanisms to recognize and respond to wounding, with those of monocots being distinct from dicots. Here, we show the involvement of two distinct categories of temporally separated, endogenously derived peptides, namely, plant elicitor peptides (PEPs) and phytosulfokine (PSK), mediating wound responses in rice. These peptides trigger a dynamic signal relay in which a receptor kinase involved in PSK perception named OsPSKR plays a major role. Perturbation of OsPSKR expression in rice leads to compromised development and constitutive autoimmune phenotypes. OsPSKR regulates the transitioning of defense to growth signals upon wounding. OsPSKR displays mutual antagonism with the OsPEPR1 receptor involved in PEP perception. Collectively, our work indicates the presence of a stepwise peptide-mediated signal relay that regulates the transition from defense to growth upon wounding in monocots.

}, keywords = {Gene Expression Regulation, Plant, Oryza, Peptides, Plant Diseases, Plant Proteins, Signal Transduction}, issn = {2211-1247}, doi = {10.1016/j.celrep.2024.114515}, author = {Harshith, Chitthavalli Y and Pal, Avik and Chakraborty, Monoswi and Nair, Ashwin and Raju, Steffi and Shivaprasad, Padubidri V} } @article {131292, title = {Active dynamics of linear chains and rings in porous media.}, journal = {J Chem Phys}, volume = {159}, year = {2023}, month = {2023 Jul 07}, abstract = {

To understand the dynamical and conformational properties of deformable active agents in porous media, we computationally investigate the dynamics of linear chains and rings made of active Brownian monomers. In porous media, flexible linear chains and rings always migrate smoothly and undergo activity-induced swelling. However, semiflexible linear chains though navigate smoothly, shrink at lower activities, followed by swelling at higher activities, while semiflexible rings exhibit a contrasting behavior. Semiflexible rings shrink, get trapped at lower activities, and escape at higher activities. This demonstrates how activity and topology interplay and control the structure and dynamics of linear chains and rings in porous media. We envision that our study will shed light on understanding the mode of transport of shape-changing active agents in porous media.

}, issn = {1089-7690}, doi = {10.1063/5.0148744}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {123130, title = {Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.}, journal = {Genome Res}, year = {2023}, month = {2023 Jan 17}, abstract = {

Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant and TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer-promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.

}, issn = {1549-5469}, doi = {10.1101/gr.276643.122}, author = {Islam, Zubairul and Saravanan, Bharath and Walavalkar, Kaivalya and Farooq, Umer and Singh, Anurag Kumar and Sabarinathan, Radhakrishnan and Thakur, Jitendra and Pandit, Awadhesh and Henikoff, Steven and Notani, Dimple} } @article {129502, title = {Administration of the glutamate-modulating drug, riluzole, after stress prevents its delayed effects on the amygdala in male rats.}, journal = {PNAS Nexus}, volume = {2}, year = {2023}, month = {2023 Jun}, pages = {pgad166}, abstract = {

Extracellular glutamate levels are elevated across brain regions immediately after stress. Despite sharing common features in their genesis, the patterns of stress-induced plasticity that eventually take shape are strikingly different between these brain areas. While stress causes structural and functional deficits in the hippocampus, it has the opposite effect on the amygdala. Riluzole, an FDA-approved drug known to modulate glutamate release and facilitate glutamate clearance, prevents stress-induced deficits in the hippocampus. But whether the same drug is also effective in countering the opposite effects of stress in the amygdala remains unexplored. We addressed this question by using a rat model wherein even a single 2-h acute immobilization stress causes a delayed expression of anxiety-like behavior, 10 days later, alongside stronger excitatory synaptic connectivity in the basolateral amygdala (BLA). This temporal profile-several days separating the acute stressor and its delayed impact-allowed us to test if these effects can be prevented by administering riluzole in drinking water acute stress. Poststress riluzole not only prevented the delayed increase in anxiety-like behavior on the elevated plus maze but also blocked the increase in spine density on BLA neurons 10 days later. Further, stress-induced increase in the frequency of miniature excitatory postsynaptic currents recorded in BLA slices, 10 days later, was also blocked by the same poststress riluzole administration. Together, these findings underscore the importance of therapeutic strategies, aimed at glutamate uptake and modulation, in correcting the delayed behavioral, physiological, and morphological effects of stress on the amygdala.

}, issn = {2752-6542}, doi = {10.1093/pnasnexus/pgad166}, author = {Datta, Siddhartha and Rashid, Zubin and Naskar, Saptarnab and Chattarji, Sumantra} } @article {134602, title = {Alteration of diet microbiota limits the experimentally evolved immune priming response in flour beetles, but not pathogen resistance.}, journal = {J Evol Biol}, year = {2023}, month = {2023 Sep 01}, abstract = {

Host-associated microbiota play a fundamental role in the training and induction of different forms of immunity, including inducible as well as constitutive components. However, direct experiments analysing the relative importance of microbiota on diverse forms of evolved immune functions are missing. We addressed this gap by using experimentally evolved lines of Tribolium castaneum that either produced inducible immune memory-like responses (immune priming) or constitutively expressed basal resistance (without priming), as divergent counterstrategies against Bacillus thuringiensis infection. We altered the microbial communities present in the diet (i.e. wheat flour) of these evolved lines using UV irradiation and estimated the impact on the beetle{\textquoteright}s ability to mount a priming response versus basal resistance. Populations that had evolved immune priming lost the ability to mount a priming response upon alteration of diet microbiota. Microbiota manipulation also caused a drastic reduction in their reproductive output and post-infection longevity. In contrast, in pathogen-resistant beetles, microbiota manipulation did not affect post-infection survival or reproduction. The divergent evolution of immune responses across beetle lines was thus associated with divergent reliance on the microbiome. Whether the latter is a direct outcome of differential pathogen exposure during selection or reflects evolved immune functions remains unclear. We hope that our results will motivate further experiments to understand the mechanistic basis of these complex evolutionary associations between microbiota, host immune strategies and fitness outcomes.

}, issn = {1420-9101}, doi = {10.1111/jeb.14213}, author = {Prakash, Arun and Agashe, Deepa and Khan, Imroze} } @article {133182, title = {An androgen receptor regulated gene score is associated with epithelial to mesenchymal transition features in triple negative breast cancers.}, journal = {Transl Oncol}, volume = {37}, year = {2023}, month = {2023 Aug 19}, pages = {101761}, abstract = {

BACKGROUND: Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived AR regulated gene score and examined its utility in BC subtypes.

METHODS: AR regulated genes were derived by applying a bioinformatic pipeline on publicly available microarray data sets of AR+ BC cell lines and gene score was calculated as average expression of six AR regulated genes. Tumors were divided into AR high and low based on gene score and associations with clinical parameters, circulating androgens, survival and epithelial to mesenchymal transition (EMT) markers were examined, further evaluated in invitro models and public datasets.

RESULTS: 53\% (133/249) tumors were classified as AR gene score high and were associated with significantly better clinical parameters, disease-free survival (86.13\ vs 72.69 months, log rank p\ =\ 0.032) when compared to AR low tumors. 36\% of TNBC (N\ =\ 66) were AR gene score high with higher expression of EMT markers (p\ =\ 0.024) and had high intratumoral levels of 5α-reductase, enzyme involved in intracrine androgen metabolism. In MDA-MB-453 treated with dihydrotestosterone, SLUG expression increased, E-cadherin decreased with increase in migration and these changes were reversed with bicalutamide. Similar results were obtained in public datasets.

CONCLUSION: Deciphering the role of AR in BC is difficult based on AR protein levels alone. Our results support the context dependent function of AR in driving better prognosis in ER positive tumors and EMT features in TNBC tumors.

}, issn = {1936-5233}, doi = {10.1016/j.tranon.2023.101761}, author = {Rajarajan, Savitha and Snijesh, V P and Anupama, C E and Nair, Madhumathy G and Mavatkar, Apoorva D and Naidu, Chandrakala M and Patil, Sharada and Nimbalkar, Vidya P and Alexander, Annie and Pillai, Maalavika and Jolly, Mohit Kumar and Sabarinathan, Radhakrishnan and Ramesh, Rakesh S and Bs, Srinath and Prabhu, Jyothi S} } @article {126685, title = {Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.}, journal = {Cell Rep}, volume = {42}, year = {2023}, month = {2023 Apr 04}, pages = {112344}, abstract = {

Pre-clinical studies of fragile X syndrome (FXS) have focused on neurons, with the role of glia remaining largely underexplored. We examined the astrocytic regulation of aberrant firing of FXS neurons derived from human pluripotent stem cells. Human FXS cortical neurons, co-cultured with human FXS astrocytes, fired frequent short-duration spontaneous bursts of action potentials compared with less frequent, longer-duration bursts of control neurons co-cultured with control astrocytes. Intriguingly, bursts fired by FXS neurons co-cultured with control astrocytes are indistinguishable from control neurons. Conversely, control neurons exhibit aberrant firing in the presence of FXS astrocytes. Thus, the astrocyte genotype determines the neuronal firing phenotype. Strikingly, astrocytic-conditioned medium, and not the physical presence of astrocytes, is capable of determining the firing phenotype. The mechanistic basis of this effect indicates that the astroglial-derived protein, S100β, restores normal firing by reversing the suppression of a persistent sodium current in FXS neurons.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2023.112344}, author = {Sharma, Shreya Das and Reddy, Bharath Kumar and Pal, Rakhi and Ritakari, Tuula E and Cooper, James D and Selvaraj, Bhuvaneish T and Kind, Peter C and Chandran, Siddharthan and Wyllie, David J A and Chattarji, Sumantra} } @article {128071, title = {Begomoviral beta C1 orchestrates organellar genomic instability to augment viral infection}, journal = {PLANT JOURNAL }, year = {2023}, month = {05/2023}, abstract = {

Chloroplast is the site for transforming light energy to chemical energy. It also acts as a production unit for a variety of defense-related molecules. These defense moieties are necessary to mount a successful counter defense against pathogens, including viruses. Previous studies indicated disruption of chloroplast homeostasis as a basic strategy of Begomovirus for its successful infection leading to the production of vein-clearing, mosaic, and chlorotic symptoms in infected plants. Although begomoviral pathogenicity determinant protein Beta C1 (beta C1) was implicated for pathogenicity, the underlying mechanism was unclear. Here we show that, begomoviral beta C1 directly interferes with the host plastid homeostasis. beta C1 induced DPD1, an organelle-specific nuclease, implicated in nutrient salvage and senescence, as well as modulated the function of a major plastid genome maintainer protein RecA1, to subvert plastid genome. We show that beta C1 was able to physically interact with bacterial RecA and its plant homolog RecA1, resulting in its altered activity. We observed that knocking-down DPD1 during virus infection significantly reduced virus-induced necrosis. These results indicate the presence of a strategy in which a viral protein alters host defense by targeting modulators of chloroplast DNA. We predict that the mechanism identified here might have similarities in other plant-pathogen interactions.

}, doi = {10.1111/tpj.16186}, author = {Nair, Ashwin and Harshith, Chitthavalli Y. Y. and Narjala, Anushree and Shivaprasad, P V} } @article {126670, title = {Begomoviral βC1 orchestrates organellar genomic instability to augment viral infection.}, journal = {Plant J}, year = {2023}, month = {2023 Mar 14}, abstract = {

Chloroplast is the site for transforming light energy to chemical energy. It also acts as a production unit for a variety of defense-related molecules. These defense moieties are necessary to mount a successful counter defense against pathogens, including viruses. Previous studies indicated disruption of chloroplast homeostasis as a basic strategy of Begomovirus for its successful infection leading to the production of vein-clearing, mosaic, and chlorotic symptoms in infected plants. Although begomoviral pathogenicity determinant protein Beta C1 (βC1) was implicated for pathogenicity, the underlying mechanism was unclear. Here we show that, begomoviral βC1 directly interferes with the host plastid homeostasis. βC1 induced DPD1, an organelle-specific nuclease, implicated in nutrient salvage and senescence, as well as modulated the function of a major plastid genome maintainer protein RecA1, to subvert plastid genome. We show that βC1 was able to physically interact with bacterial RecA and its plant homolog RecA1, resulting in its altered activity. We observed that knocking-down DPD1 during virus infection significantly reduced virus-induced necrosis. These results indicate the presence of a strategy in which a viral protein alters host defense by targeting modulators of chloroplast DNA. We predict that the mechanism identified here might have similarities in other plant-pathogen interactions.

}, issn = {1365-313X}, doi = {10.1111/tpj.16186}, author = {Nair, Ashwin and Harshith, Chitthavalli Y and Narjala, Anushree and Shivaprasad, Padubidri V} } @article {125205, title = {Benchmarking performance of an automatic polysomnography scoring system in a population with suspected sleep disorders.}, journal = {Front Neurol}, volume = {14}, year = {2023}, month = {2023}, pages = {1123935}, abstract = {

AIM: The current gold standard for measuring sleep disorders is polysomnography (PSG), which is manually scored by a sleep technologist. Scoring a PSG is time-consuming and tedious, with substantial inter-rater variability. A deep-learning-based sleep analysis software module can perform autoscoring of PSG. The primary objective of the study is to validate the accuracy and reliability of the autoscoring software. The secondary objective is to measure workflow improvements in terms of time and cost a time motion study.

METHODOLOGY: The performance of an automatic PSG scoring software was benchmarked against the performance of two independent sleep technologists on PSG data collected from patients with suspected sleep disorders. The technologists at the hospital clinic and a third-party scoring company scored the PSG records independently. The scores were then compared between the technologists and the automatic scoring system. An observational study was also performed where the time taken for sleep technologists at the hospital clinic to manually score PSGs was tracked, along with the time taken by the automatic scoring software to assess for potential time savings.

RESULTS: Pearson{\textquoteright}s correlation between the manually scored apnea-hypopnea index (AHI) and the automatically scored AHI was 0.962, demonstrating a near-perfect agreement. The autoscoring system demonstrated similar results in sleep staging. The agreement between automatic staging and manual scoring was higher in terms of accuracy and Cohen{\textquoteright}s kappa than the agreement between experts. The autoscoring system took an average of 42.7 s to score each record compared with 4,243 s for manual scoring. Following a manual review of the auto scores, an average time savings of 38.6 min per PSG was observed, amounting to 0.25 full-time equivalent (FTE) savings per year.

CONCLUSION: The findings indicate a potential for a reduction in the burden of manual scoring of PSGs by sleep technologists and may be of operational significance for sleep laboratories in the healthcare setting.

}, issn = {1664-2295}, doi = {10.3389/fneur.2023.1123935}, author = {Choo, Bryan Peide and Mok, Yingjuan and Oh, Hong Choon and Patanaik, Amiya and Kishan, Kishan and Awasthi, Animesh and Biju, Siddharth and Bhattacharjee, Soumya and Poh, Yvonne and Wong, Hang Siang} } @article {124446, title = {Bioinformatics analysis of mutations sheds light on the evolution of Dengue NS1 protein with implications in the identification of potential functional and druggable sites.}, journal = {Mol Biol Evol}, year = {2023}, month = {2023 Feb 16}, abstract = {

Non-structural protein (NS1) is a 350 amino acid long conserved protein in the dengue virus. Conservation of NS1 is expected due to its importance in dengue pathogenesis. The protein is known to exist in dimeric and hexameric states. The dimeric state is involved in its interaction with host proteins and viral replication, whereas the hexameric state is involved in viral invasion. In this work, we performed extensive structure and sequence analysis of NS1 protein, and uncovered the role of NS1 quaternary states in its evolution. A three-dimensional modeling of unresolved loop regions in NS1 structure is performed. {\textquoteright}Conserved{\textquoteright} and {\textquoteright}Variable{\textquoteright} regions within NS1 protein were identified from sequences obtained from patient samples and the role of compensatory mutations in selecting destabilizing mutations was identified. Molecular dynamics (MD) simulations were performed to extensively study the effect of a few mutations on NS1 structure stability and study compensatory mutations. Virtual saturation mutagenesis, predicting the effect of every individual amino acid substitution on NS1 stability sequentially, revealed virtual-conserved and variable sites. The increase in number of observed and virtual conserved regions across NS1 quaternary states suggests the role of higher order structure formation in its evolutionary conservation. Our sequence and structure analysis could enable in identifying possible protein-protein interfaces and druggable sites. Virtual screening of nearly 10,000 small molecules, including FDA-approved drugs, permitted us to recognize six drug-like molecules targeting the dimeric sites. These molecules could be promising due to their stable interactions with NS1 throughout the simulation.

}, issn = {1537-1719}, doi = {10.1093/molbev/msad033}, author = {Sharma, Abhishek and Krishna, Sudhir and Sowdhamini, Ramanathan} } @article {133186, title = {Biosensor-integrated transposon mutagenesis reveals as a coordinator of redox homeostasis in .}, journal = {Elife}, volume = {12}, year = {2023}, month = {2023 Aug 29}, abstract = {

() is evolutionarily equipped to resist exogenous reactive oxygen species but shows vulnerability to an increase in endogenous ROS (eROS). Since eROS is an unavoidable consequence of aerobic metabolism, understanding how manages eROS levels is essential yet needs to be characterized. By combining the Mrx1-roGFP2 redox biosensor with transposon mutagenesis, we identified 368 genes (redoxosome) responsible for maintaining homeostatic levels of eROS in . Integrating redoxosome with a global network of transcriptional regulators revealed a hypothetical protein (Rv0158) as a critical node managing eROS in Disruption of ( KO) impaired growth, redox balance, respiration, and metabolism of on glucose but not on fatty acids. Importantly, KO exhibited enhanced growth on propionate, and the Rv0158 protein directly binds to methylmalonyl-CoA, a key intermediate in propionate catabolism. Metabolite profiling, ChIP-Seq, and gene-expression analyses indicate that Rv0158 manages metabolic neutralization of propionate toxicity by regulating the methylcitrate cycle. Disruption of enhanced the sensitivity of to oxidative stress, nitric oxide, and anti-TB drugs. Lastly, KO showed poor survival in macrophages and persistence defect in mice. Our results suggest that Rv0158 is a metabolic integrator for carbon metabolism and redox balance in .

}, issn = {2050-084X}, doi = {10.7554/eLife.80218}, author = {Shee, Somnath and Veetil, Reshma T and Mohanraj, Karthikeyan and Das, Mayashree and Malhotra, Nitish and Bandopadhyay, Devleena and Beig, Hussain and Birua, Shalini and Niphadkar, Shreyas and Nagarajan, Sathya Narayanan and Sinha, Vikrant Kumar and Thakur, Chandrani and Rajmani, Raju S and Chandra, Nagasuma and Laxman, Sunil and Singh, Mahavir and Samal, Areejit and Seshasayee, Aswin N and Singh, Amit} } @article {126672, title = {Broadband Plasmonic Nanoantennas for Multi-Color Nanoscale Dynamics in Living Cells.}, journal = {Small}, year = {2023}, month = {2023 Mar 31}, pages = {e2207977}, abstract = {

Recently, the implementation of plasmonic nanoantennas has opened new possibilities to investigate the nanoscale dynamics of individual biomolecules in living cells. However, studies so far have been restricted to single molecular species as the narrow wavelength resonance of gold-based nanostructures precludes the simultaneous interrogation of different fluorescently labeled molecules. Here, broadband aluminum-based nanoantennas carved at the apex of near-field probes are exploited to resolve nanoscale-dynamic molecular interactions on living cell membranes. Through multicolor excitation, the authors simultaneously recorded fluorescence fluctuations of dual-color labeled transmembrane receptors known to form nanoclusters. Fluorescence cross-correlation studies revealed transient interactions between individual receptors in regions of ≈60\ nm. Moreover, the high signal-to-background ratio provided by the antenna illumination allowed the authors to directly detect fluorescent bursts arising from the passage of individual receptors underneath the antenna. Remarkably, by reducing the illumination volume below the characteristic receptor nanocluster sizes, the molecular diffusion within nanoclusters is resolved and distinguished from nanocluster diffusion. Spatiotemporal characterization of transient interactions between molecules is crucial to understand how they communicate with each other to regulate cell function. This work demonstrates the potential of broadband photonic antennas to study multi-molecular events and interactions in living cell membranes with unprecedented spatiotemporal resolution.

}, issn = {1613-6829}, doi = {10.1002/smll.202207977}, author = {Sanz-Paz, Maria and van Zanten, Thomas S and Manzo, Carlo and Mivelle, Mathieu and Garcia-Parajo, Maria F} } @article {135854, title = {Building Indian Biomedical Leadership to Bridge the Gap Between Science, Primary Health Care and Public Health}, journal = {JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE }, year = {2023}, month = {09/2023}, abstract = {

The Indian biomedical landscape has been characterized by the existence of somewhat polarized institutional structures and professional growth. While some scientific and public health challenges have been met with existing structures, there is still a large unmet scientific and public health need. Broadly, the physical separation of science, engineering, medical campuses and industry has led to silos of excellence and accomplishment with huge gaps in innovation and implementation. The lack of inter-disciplinary educational options has further reinforced the cultural underpinning of "guilds" that have found it difficult to collaborate. Strikingly, with almost a comparable number of institutions that train doctors in the allopathic or traditional disciplines such as Ayurveda, Unani etc., an "integrative medicine" framework has not emerged, apart from an over reliance on specialization at the expense of primary care. This paper is written by two physician-scientists, the first is located in a basic life science research center. The second, a practicing family physician, from the institutional anchor of a life sciences research institution. In this, we trace our experiences, primarily from a principal investigator{\textquoteright}s perspective, describing the scientific projects and try to explore the lessons learnt along the way. We will first describe the research in the lab{\textquoteright}s core area of human cervical cancer progression and our more recent effort with Dengue genomics and vaccine design. We then describe the lab{\textquoteright}s engagement with medical campuses and other agencies as well as review our various meetings and interactions so far with our colleagues from Africa to grasp what might be the "generalizable lessons" for the future. The Indian council of medical research initiated a program with Africa in health sciences. Building upon those interactions, we have taken some incremental steps in that direction and described our efforts.

}, doi = {10.1007/s41745-022-00320-1}, author = {Krishna, Sudhir and Prasad, Ramakrishna} } @article {128073, title = {Carbonate budgets in Lakshadweep Archipelago bear the signature of local impacts and global climate disturbances}, journal = {CORAL REEFS }, year = {2023}, month = {04/2023}, abstract = {

Predicted sea-level rise and increased storm frequency caused by climate change drastically threaten low-lying inhabited coral atolls. Coral reef frameworks are the atolls{\textquoteright} primary defence from these changes. The growth and integrity of these frameworks is reflected in their carbonate budgets, a dynamic balance between biogenic accretion through coral growth and erosional forces, both of which are affected by factors acting at different spatial scales. We explored how carbonate budgets, estimated using the ReefBudget methodology, vary between three inhabited atolls that face differing anthropogenic stressors in the Lakshadweep Archipelago in the Northern Indian Ocean. We surveyed ten reefs, at two depths each, across the three islands. Overall, net carbonate budgets of reefs across all atolls were below optimal production rates needed to continue protecting shorelines (5 G measured on healthy reefs). This was a result of repeated mass bleaching events as well as local impacts. Carbonate production was influenced by a recent mass bleaching event in 2016 and a cyclone in 2018, and varied between depths and exposures, potentially due to differential recovery and mortality dynamics. Erosional processes were locally mediated with both urchin and parrotfish density showing large differences between islands, possibly linked to nutrient outflow and fishing intensity. We also find that by the year 2100, a large proportion of shallow sites will experience an increase in water depth above half a metre under moderate and high emissions scenarios, but none will breach this threshold under a low emissions scenario. Our results show that patterns of carbonate production were largely mediated by the history of global/regional disturbances, while erosional rates were much more dependent on local factors.

}, doi = {10.1007/s00338-023-02374-8}, author = {Patel, Farai Divan and Pinto, Wenzel and Dey, Mayukh and Alcoverro, Teresa and Arthur, Rohan} } @article {125204, title = {Cellular compartmentalisation and receptor promiscuity as a strategy for accurate and robust inference of position during morphogenesis. }, journal = {Elife}, year = {2023}, month = {03/2023}, pages = {12:e79257}, abstract = {

Precise spatial patterning of cell fate during morphogenesis requires accurate inference of cellular position. In making such inferences from morphogen profiles, cells must contend with inherent stochasticity in morphogen production, transport, sensing and signalling. Motivated by the multitude of signalling mechanisms in various developmental contexts, we show how cells may utilise multiple tiers of processing (compartmentalisation) and parallel branches (multiple receptor types), together with feedback control, to bring about fidelity in morphogenetic decoding of their positions within a developing tissue. By simultaneously deploying specific and nonspecific receptors, cells achieve a more accurate and robust inference. We explore these ideas in the patterning of Drosophila melanogaster wing imaginal disc by Wingless morphogen signalling, where multiple endocytic pathways participate in decoding the morphogen gradient. The geometry of the inference landscape in the high dimensional space of parameters provides a measure for robustness and delineates stiff and sloppy directions. This distributed information processing at the scale of the cell highlights how local cell autonomous control facilitates global tissue scale design.

}, doi = {10.7554/eLife.79257}, author = {Iyer, Krishnan S and Prabhakara, C and Mayor, Satyajit and Rao, Madan} } @article {129154, title = {A census of actin-associated proteins in humans.}, journal = {Front Cell Dev Biol}, volume = {11}, year = {2023}, month = {2023}, pages = {1168050}, abstract = {

Actin filaments help in maintaining the cell structure and coordinating cellular movements and cargo transport within the cell. Actin participates in the interaction with several proteins and also with itself to form the helical filamentous actin (F-actin). Actin-binding proteins (ABPs) and actin-associated proteins (AAPs) coordinate the actin filament assembly and processing, regulate the flux between globular G-actin and F-actin in the cell, and help maintain the cellular structure and integrity. We have used protein-protein interaction data available through multiple sources (STRING, BioGRID, mentha, and a few others), functional annotation, and classical actin-binding domains to identify actin-binding and actin-associated proteins in the human proteome. Here, we report 2482 AAPs and present an analysis of their structural and sequential domains, functions, evolutionary conservation, cellular localization, abundance, and tissue-specific expression patterns. This analysis provides a base for the characterization of proteins involved in actin dynamics and turnover in the cell.

}, issn = {2296-634X}, doi = {10.3389/fcell.2023.1168050}, author = {Meenakshi S, Iyer and Rao, Madan and Mayor, Satyajit and Sowdhamini, Ramanathan} } @article {126671, title = {Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.}, journal = {Front Cell Dev Biol}, volume = {11}, year = {2023}, month = {2023}, pages = {1095419}, abstract = {

Hypoxia afflicts the microenvironment of solid tumors fueling malignancy. We investigated the impact of long hypoxia exposure on transcriptional remodeling, tumor mutational burden (TMB), and genomic instability of cancer cells that were grouped based on their inherent sensitivity or resistance to hypoxia. A hypoxia score was used as a metric to distinguish between the most hypoxia-sensitive (hypoxia high (HH)), and most resistant (hypoxia low (HL)) cancer cells. By applying whole exome sequencing and microarray analysis, we showed that the HH group was indeed more sensitive to hypoxia, having significantly higher TMB ( = 0.03) and copy number losses ( = 0.03), as well as a trend of higher transcriptional response. Globally cells adapted by decreasing expression of genes involved in metabolism, proliferation, and protein maturation, and increasing alternative splicing. They accumulated mutations, especially frameshift insertions, and harbored increased copy number alterations, indicating increased genomic instability. Cells showing highest TMB simultaneously experienced a significant downregulation of DNA replication and repair and chromosomal maintenance pathways. A sixteen-gene common response to chronic hypoxia was put forth, including genes regulating angiogenesis and proliferation. Our findings show that chronic hypoxia enables survival of tumor cells by metabolic reprogramming, modulating proliferation, and increasing genomic instability. They additionally highlight key adaptive pathways that can potentially be targeted to prevent cancer cells residing in chronically hypoxic tumor areas from thriving.

}, issn = {2296-634X}, doi = {10.3389/fcell.2023.1095419}, author = {Abou Khouzam, Raefa and Sharda, Mohak and Rao, Shyama Prasad and Kyerewah-Kersi, Stephanie Maame and Zeinelabdin, Nagwa Ahmed and Mahmood, Ayda Shah and Nawafleh, Husam and Khan, Munazza Samar and Venkatesh, Goutham Hassan and Chouaib, Salem} } @article {136529, title = {Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers.}, journal = {Mol Oncol}, year = {2023}, month = {2023 Nov 27}, abstract = {

HPV infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated HPV DNA on host chromatin structure and gene regulation remains less understood. We investigated genome-wide patterns of HPV integrations and associated host gene expression changes in the context of host chromatin states and TADs. HPV integrations were significantly enriched in active chromatin regions and depleted in inactive ones. Interestingly, regardless of chromatin state, genomic regions flanking HPV integrations showed transcriptional upregulation. Nevertheless, upregulation (both local and long-range) was mostly confined to TADs with integration, but not affecting adjacent TADs. Few TADs showed recurrent integrations associated with overexpression of oncogenes within them (e.g. MYC, PVT1, TP63 and ERBB2) regardless of proximity. Hi-C and 4C-seq analyses in cervical cancer cell line (HeLa) demonstrated chromatin looping interactions between integrated HPV and MYC/PVT1 regions (~500kb apart), leading to allele-specific overexpression. Based on these, we propose HPV integrations can trigger multimodal oncogenic activation to promote cancer progression.

}, issn = {1878-0261}, doi = {10.1002/1878-0261.13559}, author = {Singh, Anurag Kumar and Walavalkar, Kaivalya and Tavernari, Daniele and Ciriello, Giovanni and Notani, Dimple and Sabarinathan, Radhakrishnan} } @article {129159, title = {Citizen science facilitates first ever genetic detection of wolf-dog hybridization in Indian savannahs.}, journal = {Ecol Evol}, volume = {13}, year = {2023}, month = {2023 May}, pages = {e10100}, abstract = {

Human demographic expansion has confined wildlife to fragmented habitats, often in proximity to human-modified landscapes. Such interfaces facilitate increased interactions between feral or domesticated animals and wildlife, posing a high risk to wild species. This is especially relevant for free-ranging dogs () and wild canids like gray wolves () and golden jackals (). Wolf-dog hybridization may lead to a significant reduction of specific adaptations in wolves that could result in the decline of wolf populations. Detection and genetic discrimination of hybrids between dogs and wolves are challenging because of their complex demographic history and close ancestry. Citizen scientists identified two phenotypically different-looking individuals and subsequently collected non-invasive samples that were used by geneticists to test wolf-dog hybridization. Genomic data from shed hair samples of suspected hybrid individuals using double-digest restriction-site-associated DNA (ddRAD) sequencing resulted in 698 single nucleotide polymorphism (SNP) markers. We investigated the genetic origin of these two individuals analyzed with genetically known dogs, wolves, and other canid species including jackals and dholes (). Our results provide the first genetic evidence of one F2 hybrid and the other individual could be a complex hybrid between dogs and wolves. Our results re-iterate the power of next-generation sequencing (NGS) for non-invasive samples as an efficient tool for detecting hybrids. Our results suggest the need for more robust monitoring of wolf populations and highlight the tremendous potential for collaborative approaches between citizens and conservation scientists to detect and monitor threats to biodiversity.

}, issn = {2045-7758}, doi = {10.1002/ece3.10100}, author = {Tyagi, Abhinav and Godbole, Mihir and Vanak, Abi Tamim and Ramakrishnan, Uma} } @article {134601, title = {Clustering of lipids driven by integrin.}, journal = {Soft Matter}, volume = {19}, year = {2023}, month = {2023 Sep 13}, pages = {6814-6824}, abstract = {

Integrin is an important transmembrane receptor protein which remodels the actin network and anchors the cell membrane towards the extracellular matrix mechanochemical pathways. The clustering of specific lipids and lipid-anchored proteins, which is essential for a certain type of endocytosis process, is facilitated at integrin-mediated active regions. To study this, we propose a minimal exactly solvable model which includes the interplay of stochastic shuttling between integrin on and off states with the intrinsic dynamics of the membrane. We propose a two-step mechanism in which the integrin induces an aster-like arrangement in the actin network, followed by clustering of lipids in that region. We obtain an analytic expression for the deformation and local membrane velocity, and thereby the evolution of clustering mediated by a single integrin. The deformation evolves nonmonotonically and its dependence on the stochastic shuttling timescales and membrane properties is elucidated. Our estimates of the area of the deformed region and the number of lipids in it indicate strong clustering.

}, keywords = {Actins, Cell Membrane, Cluster Analysis, Integrins, Lipids, Membrane Proteins}, issn = {1744-6848}, doi = {10.1039/d3sm00809f}, author = {Singha, Tapas and Polley, Anirban and Barma, Mustansir} } @article {135855, title = {A comparison between time-constrained counts and line transects as methods to estimate butterfly diversity and monitor populations in tropical habitats}, journal = {INSECT CONSERVATION AND DIVERSITY}, year = {2023}, month = {09/2023}, abstract = {

Long-term species monitoring programmes have revealed catastrophic declines in insect populations and disruption of biological communities that are contributing to biodiversity loss. Such discoveries have been possible because of standardised methods, such as line transects, of counting butterflies and other insects. However, line transects are not feasible in many tropical and mountainous habitats, so alternative methods must be explored.To tackle this issue, we devised time-constrained (30-min) counts and compared butterfly diversity estimated through timed counts and line transects in three tropical habitats in India (evergreen forest, dry deciduous forest and an urban woodland). We tested the relative performance of the two methods in sampling species richness and abundance, as well as numbers of rare, endemic and specialist butterflies.We observed greater overall species richness, and more species of habitat specialists and endemics per sample in time-constrained counts in the evergreen forest, but not in the other two habitats. Thus, time-constrained counts were relatively more efficient in detecting species in the species-rich evergreen habitat. Apart from this difference, the two sampling methods captured similar levels of species richness and other measures of diversity.Our study thus shows that time-constrained counts are a suitable if not a superior alternative to line transects to conduct butterfly diversity surveys and population monitoring in complex tropical landscapes. Due to methodological flexibility and simplicity, time-constrained counts may be particularly useful to study the impacts of climate change, habitat fragmentation and land use practices on butterfly, Odonata and other insect populations in populous and tech-ready tropical countries using citizen science frameworks.

Insights into the impacts of habitat and climate change, efficacy of management practices and so forth on the persistence of insect populations depend on long-term monitoring programmes that gather data using standardised methods.We devised time-constrained (30-min) counts as a standard method for sampling diversity and monitoring butterfly populations in tropical habitats where species diversity is high but linear transects are impractical.Our study showed that timed counts are as efficient as line transects in capturing species diversity and more efficient in sampling specialist and endemic species in tropical evergreen forests.image

}, doi = {10.1111/icad.12693}, author = {Attiwilli, Suman and Ravikanthachari, Nitin and Kunte, Krushnamegh} } @article {131927, title = {Compositional variation in grassland plant communities}, journal = {ECOSPHERE }, volume = {14}, year = {2023}, month = {06/2023}, pages = {e4542}, abstract = {

Human activities are altering ecological communities around the globe. Understanding the implications of these changes requires that we consider the composition of those communities. However, composition can be summarized by many metrics which in turn are influenced by different ecological processes. For example, incidence-based metrics strongly reflect species gains or losses, while abundance-based metrics are minimally affected by changes in the abundance of small or uncommon species. Furthermore, metrics might be correlated with different predictors. We used a globally distributed experiment to examine variation in species composition within 60 grasslands on six continents. Each site had an identical experimental and sampling design: 24 plots x 4 years. We expressed compositional variation within each site-not across sites-using abundance- and incidence-based metrics of the magnitude of dissimilarity (Bray-Curtis and Sorensen, respectively), abundance- and incidence-based measures of the relative importance of replacement (balanced variation and species turnover, respectively), and species richness at two scales (per plot-year [alpha] and per site [gamma]). Average compositional variation among all plot-years at a site was high and similar to spatial variation among plots in the pretreatment year, but lower among years in untreated plots. For both types of metrics, most variation was due to replacement rather than nestedness. Differences among sites in overall within-site compositional variation were related to several predictors. Environmental heterogeneity (expressed as the CV of total aboveground plant biomass in unfertilized plots of the site) was an important predictor for most metrics. Biomass production was a predictor of species turnover and of alpha diversity but not of other metrics. Continentality (measured as annual temperature range) was a strong predictor of Sorensen dissimilarity. Metrics of compositional variation are moderately correlated: knowing the magnitude of dissimilarity at a site provides little insight into whether the variation is driven by replacement processes. Overall, our understanding of compositional variation at a site is enhanced by considering multiple metrics simultaneously. Monitoring programs that explicitly incorporate these implications, both when designing sampling strategies and analyzing data, will have a stronger ability to understand the compositional variation of systems and to quantify the impacts of human activities.

}, doi = {10.1002/ecs2.4542}, author = {Bakker, Jonathan D. and Price, Jodi N. and Henning, Jeremiah A. and .. and Sankaran, M and al et} } @article {126668, title = {A comprehensive phylogeny and revised taxonomy illuminate the origin and diversification of the global radiation of Papilio (Lepidoptera: Papilionidae).}, journal = {Mol Phylogenet Evol}, volume = {183}, year = {2023}, month = {2023 Mar 11}, pages = {107758}, abstract = {

The swallowtail genus Papilio (Lepidoptera: Papilionidae) is species rich, distributed worldwide, and has broad morphological habits and ecological niches. Because of its elevated species richness, it has been historically difficult to reconstruct a densely sampled phylogeny for this clade. Here we provide a taxonomic working list for the genus, resulting in 235 Papilio species, and assemble a molecular dataset of seven gene fragments representing ca. 80\% of the currently described diversity. Phylogenetic analyses reconstructed a robust tree with highly supported relationships within subgenera, although a few nodes in the early history of the Old World Papilio remain unresolved. Contrasting with previous results, we found that Papilio alexanor is sister to all Old World Papilio and that the subgenus Eleppone is no longer monotypic. The latter includes the recently described Fijian Papilio natewa with the Australian Papilio anactus and is sister to subgenus Araminta (formerly included in subgenus Menelaides) occurring in Southeast Asia. Our phylogeny also includes rarely studied (P. antimachus, P. benguetana) or endangered species (P. buddha, P. chikae). Taxonomic changes resulting from this study are elucidated. Molecular dating and biogeographic analyses indicate that Papilio originated ca. 30 million years ago (Oligocene), in a northern region centered on Beringia. A rapid early Miocene radiation in the Paleotropics is revealed within Old World Papilio, potentially explaining their low early branch support. Most subgenera originated in the early to middle Miocene followed by synchronous southward biogeographic dispersals and repeated local extirpations in northern latitudes. This study provides a comprehensive phylogenetic framework for Papilio with clarification of subgeneric systematics and species taxonomic changes enumerated, which will facilitate further studies to address questions on their ecology and evolutionary biology using this model clade.

}, issn = {1095-9513}, doi = {10.1016/j.ympev.2023.107758}, author = {Condamine, Fabien L and Allio, R{\'e}mi and Reboud, Eliette L and Dupuis, Julian R and Toussaint, Emmanuel F A and Mazet, Nathan and Hu, Shao-Ji and Lewis, Delano S and Kunte, Krushnamegh and Cotton, Adam M and Sperling, Felix A H} } @article {128074, title = {Computational analysis of the flexibility in the disordered linker region connecting LIM domains in cysteine-glycine-rich protein.}, journal = {Front Genet}, volume = {14}, year = {2023}, month = {2023}, pages = {1134509}, abstract = {

One of the key proteins that are present in the Z-disc of cardiac tissues, CSRP3, has been implicated in dilated and hypertrophic cardiomyopathy leading to heart failure. Although multiple cardiomyopathy-related mutations have been reported to reside on the two LIM domains and the disordered regions connecting the domains in this protein, the exact role of the disordered linker region is not clear. The linker harbors a few post-translational modification sites and is expected to be a regulatory site. We have carried out evolutionary studies on 5614 homologs spanning across taxa. We also performed molecular dynamics simulations of full-length CSRP3 to show that the length variations and conformational flexibility of the disordered linker could provide additional levels of functional modulation. Finally, we show that the CSRP3 homologs with widely different lengths of the linker regions could display diversity in their functional specifications. The present study provides a useful perspective to our understanding of the evolution of the disordered region between CSRP3 LIM domains.

}, issn = {1664-8021}, doi = {10.3389/fgene.2023.1134509}, author = {Chauhan, Pankaj Kumar and Sowdhamini, R} } @article {129164, title = {A computational view of short-term plasticity and its implications for E-I balance.}, journal = {Curr Opin Neurobiol}, volume = {81}, year = {2023}, month = {2023 May 26}, pages = {102729}, abstract = {

Short-term plasticity (STP) and excitatory-inhibitory balance (EI balance) are both ubiquitous building blocks of brain circuits across the animal kingdom. The synapses involved in EI are also subject to short-term plasticity, and several experimental studies have shown that their effects overlap. Recent computational and theoretical work has begun to highlight the functional implications of the intersection of these motifs. The findings are nuanced: while there are general computational themes, such as pattern tuning, normalization, and gating, much of the richness of these interactions comes from region- and modality specific tuning of STP properties. Together these findings point towards the STP-EI balance combination as being a versatile and highly efficient neural building block for a wide range of pattern-specific responses.

}, issn = {1873-6882}, doi = {10.1016/j.conb.2023.102729}, author = {Asopa, Aditya and Bhalla, Upinder S} } @article {124206, title = {A conserved SNP variation in the pre-miR396c flanking region in Oryza sativa indica landraces correlates with mature miRNA abundance.}, journal = {Sci Rep}, volume = {13}, year = {2023}, month = {2023 Feb 07}, pages = {2195}, abstract = {

Plant precursor miRNAs (pre-miRNA) have conserved evolutionary footprints that correlate with mode of miRNA biogenesis. In plants, base to loop and loop to base modes of biogenesis have been reported. Conserved structural element(s) in pre-miRNA play a major role in turn over and abundance of mature miRNA. Pre-miR396c sequences and secondary structural characteristics across Oryza species are presented. Based on secondary structure, twelve Oryza pre-miR396c sequences are divided into three groups, with the precursor from halophytic Oryza coarctata forming a distinct group.\ The miRNA-miRNA* duplex region is completely conserved across eleven\ Oryza\ species as are other structural elements in the pre-miRNA, suggestive of an evolutionarily conserved base-to-loop mode of miRNA biogenesis. SNPs within O. coarctata mature miR396c sequence and miRNA* region have the potential to alter target specificity and association with the RNA-induced silencing complex. A conserved SNP variation, rs10234287911 (G/A), identified in O. sativa pre-miR396c sequences alters base pairing above the miRNA-miRNA* duplex. The more stable structure conferred by the {\textquoteright}A{\textquoteright} allele may promote better processing vis-{\`a}-vis the structure conferred by {\textquoteright}G{\textquoteright} allele. We also examine pri- and pre-miR396c expression in cultivated rice under heat and salinity and their correlation with miR396c expression.

}, keywords = {MicroRNAs, Oryza, Polymorphism, Single Nucleotide, Salt-Tolerant Plants}, issn = {2045-2322}, doi = {10.1038/s41598-023-28836-1}, author = {Jaganathan, Deepa and Rajakani, Raja and Doddamani, Dadakhalandar and Saravanan, Divya and Pulipati, Shalini and Vivek Hari Sundar G and Sellamuthu, Gothandapani and Jayabalan, Shilpha and Kumari, Kumkum and Parthasarathy, Pavithra and S, Punitha and Ramalingam, Sivaprakash and Shivaprasad, Padubidri V and Venkataraman, Gayatri} } @article {121922, title = {Contryphan sequence diversity: Messy N-terminus processing, effects on chromatographic behaviour and mass spectrometric fragmentation.}, journal = {J Proteomics}, year = {2023}, month = {2022 Dec 29}, pages = {104805}, abstract = {

Contryphans, peptides containing a single disulfide bond, are found abundantly in cone snail venom. The analysis of a large dataset of available contryphan sequences permits a classification based on the occurrence of proline residues at positions 2 and 5 within the macrocyclic 23-membered disulfide loop. Further sequence diversity is generated by variable proteolytic processing of the contryphan precursor proteins. In the majority of contryphans, presence of Pro at position 2 and a D-residue at position 3 leads to a slow conformational dynamics, manifesting as anomalous chromatographic profiles during LC analysis. LC-MS analysis of diverse contryphans suggests that elution profiles may be used as a rapid diagnostic for the presence of the Pro2-Xxx3 motif. Natural sequences from C.inscriptus and C.frigidus together with synthetic analogs permit the delineation of the features necessary for abnormal chromatographic behaviour. A diagnostic for the presence of Pro at position 5 is obtained by the observation of non-canonical fragment ions, generated by N-C bond cleavage at the dehydroalanine residue formed by disulfide cleavage. Anomalous LC profiles supports Pro at position 2, while non-canonical mass spectral fragments established Pro at position 5, providing a rapid method for contryphan analysis from LC-ESI-MS/MS profiles of crude Conus venom. SIGNIFICANCE: Contryphans are peptides, widely distributed in cone snail venom, which display extensive sequence diversity. Heterogeneity of proteolytic processing of contryphan precursor proteins, together with post-translational modifications contributes to contryphan diversity. Contryphans, identified by a combination of mass spectrometry and transcriptomic analysis, are classified on the basis of sequence features, primarily the number of proline residues within the disulfide loop. Conformational diversity arises in contryphans by cis-trans isomerization of Cys-Pro bonds, resulting in characteristic chromatographic profiles, permitting identification even in crude venom mixtures. Rapid identification of contryphans in cone snail peptide libraries is also facilitated by diagnostic mass spectral fragments arising by non-canonical cleavage of the N-C bond at Cys(6).

}, issn = {1876-7737}, doi = {10.1016/j.jprot.2022.104805}, author = {Vijayasarathy, M and Kumar, Sanjeev and Venkatesha, M A and Balaram, P} } @article {137347, title = {Cysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression prevents hypervirulence.}, journal = {Sci Adv}, volume = {9}, year = {2023}, month = {2023 Dec 15}, pages = {eadh2858}, abstract = {

Iron-sulfur (Fe-S) biogenesis requires multiprotein assembly systems, SUF and ISC, in most prokaryotes. () encodes a complete SUF system, the depletion of which was bactericidal. The ISC operon is truncated to a single gene (cysteine desulfurase), whose function remains uncertain. Here, we show that Δ is bioenergetically deficient and hypersensitive to oxidative stress, antibiotics, and hypoxia. Δ resisted killing by nitric oxide (NO). RNA sequencing indicates that IscS is important for expressing regulons of DosR and Fe-S-containing transcription factors, WhiB3 and SufR. Unlike wild-type , Δ could not enter a stable persistent state, continued replicating in mice, and showed hypervirulence. The operon was overexpressed in Δ during infection in a NO-dependent manner. Suppressing expression in Δ either by CRISPR interference or upon infection in inducible NO-deficient mice arrests hypervirulence. Together, redesigned the ISC system to "fine-tune" the expression of SUF machinery for establishing persistence without causing detrimental disease in the host.

}, keywords = {Animals, Energy Metabolism, Escherichia coli, Iron-Sulfur Proteins, Mice, Mycobacterium tuberculosis}, issn = {2375-2548}, doi = {10.1126/sciadv.adh2858}, author = {Das, Mayashree and Sreedharan, Sreesa and Shee, Somnath and Malhotra, Nitish and Nandy, Meghna and Banerjee, Ushashi and Kohli, Sakshi and Rajmani, Raju S and Chandra, Nagasuma and Seshasayee, Aswin Sai Narain and Laxman, Sunil and Singh, Amit} } @article {136528, title = {Cysteine-free cone snail venom peptides: Classification of precursor proteins and identification of mature peptides.}, journal = {J Pept Sci}, year = {2023}, month = {2023 Nov 27}, pages = {e3554}, abstract = {

The cysteine-free acyclic peptides present in marine cone snail venom have been much less investigated than their disulfide bonded counterparts. Precursor protein sequences derived from transcriptomic data, together with mass spectrometric fragmentation patterns for peptides present in venom duct tissue extracts, permit the identification of mature peptides. Twelve distinct gene superfamiles have been identified with precursor lengths between 64 and 158 residues. In the case of Conus monile, three distinct mature peptides have been identified, arising from two distinct protein precursors. Mature acyclic peptides are often post-translationally modified, with C-terminus amidation, a feature characteristic of neuropeptides. In the present study, 20 acyclic peptides from Conus monile and Conus betulinus were identified. The common modifications of C-terminus amidation, gamma carboxylation of glutamic acid (E to ϒ), N-terminus conversion of Gln (Q) to a pyroglutamyl residue (Z), and hydroxylation of Pro (P) to Hyp (O) are observed in one or more peptides identified in this study. Proteolytic trimming of sequences by cleavage at the C-terminus of Asn (N) residues is established. The presence of an asparagine endopeptidase is strengthened by the identification of legumain-like sequences in the transcriptome assemblies from diverse Conus species. Such sequences may be expected to have a cleavage specificity at Asn-Xxx peptide bonds.

}, issn = {1099-1387}, doi = {10.1002/psc.3554}, author = {Vijayasarathy, Marimuthu and Kumar, Sanjeev and Das, Rajdeep and Balaram, Padmanabhan} } @article {130549, title = {Decoding the Assembly of Mixed and Branched Heterotypic Ubiquitin Chains.}, journal = {Anal Chem}, volume = {95}, year = {2023}, month = {2023 Jul 04}, pages = {10061-10067}, abstract = {

Ubiquitination is a post-translational modification that regulates cell signaling, immune response, protein processing, molecular trafficking, and DNA repair. Generally, molecular trafficking and DNA repair processes need the attachment of a single ubiquitin on a substrate, known as monoubiquitination. The other functions of ubiquitin require the assembly of polymeric ubiquitin chains on the substrate, known as polyubiquitination. The chains are linked through the lysine residues of ubiquitin, and depending on which lysine is connected, the chains could be heterotypic or homotypic. Heterotypic polyubiquitin chains can be mixed, branched, or combined, generating myriad cellular signals with functions distinct from the homotypic ubiquitin chains. The molecular rules of heterotypic chain assembly are poorly understood due to the lack of techniques to monitor their assembly. New approaches are required to monitor the conjugation site of new ubiquitin molecules on a pre-existing chain. Here, we describe a new method based on isotopic labeling and mass spectrometry to study the assembly of heterotypic chains called isotopically resolved mass spectrometry of peptides (IRMSP). The technique is demonstrated using multiple ubiquitin enzymes and ubiquitin chains as substrates. It causes minimal perturbation to the enzyme/substrate and will be instrumental in studying the assembly of large polymeric ubiquitin chains. Using this technique, it is feasible to monitor how and with what rate branched ubiquitin chains grow in different directions in a single experiment.

}, issn = {1520-6882}, doi = {10.1021/acs.analchem.3c01425}, author = {Singh, Gajendra and Kumar, Sanjeev and Das, Ranabir} } @article {130548, title = {Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.}, journal = {Arterioscler Thromb Vasc Biol}, year = {2023}, month = {2023 Jun 22}, abstract = {

BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate.

METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice.

RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts.

CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.123.319319}, author = {Arolkar, Gauri and Krishna Kumar, Sneha and Wang, Hanjay and Gonzalez, Karen M and Kumar, Suraj and Bishnoi, Bhavnesh and Rios Coronado, Pamela E and Woo, Y Joseph and Red-Horse, Kristy and Das, Soumyashree} } @article {131301, title = {Differential Spectrum of Albumin Glycation, Oxidation, and Truncation in Type 2 and Type 1 Diabetes: Clinical and Biological Implications.}, journal = {Metab Syndr Relat Disord}, year = {2023}, month = {2023 Jul 20}, abstract = {

Albumin, the most abundant and physiologically vital serum protein, accumulates a range of chemical modifications, as consequence of encounters with large number of reactive molecules whose concentrations increase in serum under pathological conditions. In a "proof of concept" study, mass spectrometric analysis was utilized to quantitate albumin post-translational modifications (glycation, oxidation, and truncation; individual isoforms and total) in four informative subject groups [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity and healthy; all with estimated glomerular filtration rate >=60 mL/(min{\textperiodcentered}m)]. Besides glycated albumin (GA/mass spectrometry), glycated serum protein (GSP/nitro blue tetrazolium colorimetry), and glycated hemoglobin (HbA1c/high-performance liquid chromatography) were also measured. A wide spectrum of albumin molecular modifications was identified in diabetes, with significant differences between T2DM and T1DM. GA correlated more strongly with HbA1c in T1DM, compared to T2DM. Higher albumin glycation isoforms (human serum albumin +3G/2G) were more stable and discriminative markers of mean glycemia. T2DM, in comparison with T1DM, showed enhanced oxidative and dual (glycation plus oxidation) modifications, representing extreme molecular pathology. There was dramatic reduction ("deficiency") of truncated albumin isoforms in T2DM, and significant reduction in T1DM. Albumin truncation negatively correlated with severity of albumin glycation (mean glycemia) and albumin oxidation (cysteinylation). Possible mechanisms of insulin resistance, with associated increased free fatty acids binding to albumin, in stimulating albumin oxidation and inhibiting albumin glycation ("metabolic cross talks") are reviewed. Albumin molecular modifications in diabetes, together with significant differences between T2DM and T1DM, suggest possible role for insulin resistance in their genesis and consequent cell, tissue, and vascular dysfunction/damage. Albumin molecular fingerprinting can provide valuable insights into pathogenesis, diagnosis, monitoring, and future therapies for diabetes. Identification of biomarker battery ("albuminomics," "diabetomics") driven diverse "healthy," prediabetes, obesity, and T2DM phenotypes represents additional novel step toward precision medicine in diabetes and related disorders.

}, issn = {1557-8518}, doi = {10.1089/met.2023.0079}, author = {Vaishnav, Madhumati S and Kumari, Namita and Srikanta, Sathyanarayana and Krishnaswamy, Patnam R and Balaram, Padmanabhan and Bhat, Navakanta} } @article {137348, title = {Diffusion controls local versus dispersed inheritance of histones during replication and shapes epigenomic architecture.}, journal = {PLoS Comput Biol}, volume = {19}, year = {2023}, month = {2023 Dec 18}, pages = {e1011725}, abstract = {

The dynamics of inheritance of histones and their associated modifications across cell divisions can have major consequences on maintenance of the cellular epigenomic state. Recent experiments contradict the long-held notion that histone inheritance during replication is always local, suggesting that active and repressed regions of the genome exhibit fundamentally different histone dynamics independent of transcription-coupled turnover. Here we develop a stochastic model of histone dynamics at the replication fork and demonstrate that differential diffusivity of histones in active versus repressed chromatin is sufficient to quantitatively explain these recent experiments. Further, we use the model to predict patterns in histone mark similarity between pairs of genomic loci that should be developed as a result of diffusion, but cannot originate from either PRC2 mediated mark spreading or transcriptional processes. Interestingly, using a combination of CHIP-seq, replication timing and Hi-C datasets we demonstrate that all the computationally predicted patterns are consistently observed for both active and repressive histone marks in two different cell lines. While direct evidence for histone diffusion remains controversial, our results suggest that dislodged histones in euchromatin and facultative heterochromatin may exhibit some level of diffusion within "Diffusion-Accessible-Domains" (DADs), leading to redistribution of epigenetic marks within and across chromosomes. Preservation of the epigenomic state across cell divisions therefore might be achieved not by passing on strict positional information of histone marks, but by maintaining the marks in somewhat larger DADs of the genome.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1011725}, author = {Singh, Archit and Chakrabarti, Shaon} } @article {122349, title = {A dimer between monomers and hexamers-Oligomeric variations in glucosamine-6-phosphate deaminase family.}, journal = {PLoS One}, volume = {18}, year = {2023}, month = {2023}, pages = {e0271654}, abstract = {

In bacteria that live in hosts whose terminal sugar is a sialic acid, Glucosamine-6-phosphate deaminase (NagB) catalyzes the last step in converting sialic acid into Fructose-6-phosphate. These bacteria then use the Fructose-6-phosphate as an energy source. The enzyme NagB exists as a hexamer in Gram-negative bacteria and is allosterically regulated. In Gram-positive bacteria, it exists as a monomer and lacks allosteric regulation. Our identification of a dimeric Gram-negative bacterial NagB motivated us to characterize the structural basis of two closely related oligomeric forms. We report here the crystal structures of NagB from two Gram-negative pathogens, Haemophilus influenzae (Hi) and Pasturella multocida (Pm). The Hi-NagB is active as a hexamer, while Pm-NagB is active as a dimer. Both Hi-NagB and Pm-NagB contain the C-terminal helix implicated as essential for hexamer formation. The hexamer is described as a dimer of trimers. In the Pm-NagB dimer, the dimeric interface is conserved. The conservation of the dimer interface suggests that the three possible oligomeric forms of NagB are a monomer, a dimer, and a trimer of dimers. Computational modeling and MD simulations indicate that the residues at the trimeric interface have less stabilizing energy of oligomer formation than those in the dimer interface. We propose that Pm-NagB is the evolutionary link between the monomer and the hexamer forms.

}, keywords = {Aldose-Ketose Isomerases, Bacterial Proteins, Haemophilus influenzae, N-Acetylneuraminic Acid, Pasteurella multocida, Polymers}, issn = {1932-6203}, doi = {10.1371/journal.pone.0271654}, author = {Srinivasachari, Sathya and Tiwari, Vikas R and Kharbanda, Tripti and Sowdamini, Ramanathan and Subramanian, Ramaswamy} } @article {129506, title = {Diverse communication strategies in bees as a window into adaptations to an unpredictable world.}, journal = {Proc Natl Acad Sci U S A}, volume = {120}, year = {2023}, month = {2023 Jun 13}, pages = {e2219031120}, abstract = {

Communication is a fundamental feature of animal societies and helps their members to solve the challenges they encounter, from exploiting food sources to fighting enemies or finding a new home. Eusocial bees inhabit a wide range of environments and they have evolved a multitude of communication signals that help them exploit resources in their environment efficiently. We highlight recent advances in our understanding of bee communication strategies and discuss how variation in social biology, such as colony size or nesting habits, and ecological conditions are important drivers of variation in communication strategies. Anthropogenic factors, such as habitat conversion, climate change, or the use of agrochemicals, are changing the world bees inhabit, and it is becoming clear that this affects communication both directly and indirectly, for example by affecting food source availability, social interactions among nestmates, and cognitive functions. Whether and how bees adapt their foraging and communication strategies to these changes represents a new frontier in bee behavioral and conservation research.

}, keywords = {Acclimatization, Animals, Bees, Communication, Ecosystem}, issn = {1091-6490}, doi = {10.1073/pnas.2219031120}, author = {Alves, Denise A and George, Ebi A and Kaur, Rajbir and Brockmann, Axel and Hrncir, Michael and Gr{\"u}ter, Christoph} } @article {131936, title = {An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion.}, journal = {Dev Cell}, year = {2023}, month = {2023 Jul 17}, abstract = {

Adherens junctions (AJs) allow cell contact to inhibit epithelial migration yet\ also permit epithelia to move as coherent sheets. How, then, do cells identify which contacts will inhibit locomotion? Here, we show that in human epithelial cells this arises from the orientation of cortical flows at AJs. When the leader cells from different migrating sheets make head-on contact with one another, they assemble AJs that couple together oppositely directed cortical flows. This applies a tensile signal to the actin-binding domain (ABD) of α-catenin, which provides a clutch to promote lateral adhesion growth and inhibit the lamellipodial activity necessary for migration. In contrast, AJs found between leader cells in the same migrating sheet have cortical flows aligned in the same direction, and no such mechanical inhibition takes place. Therefore, α-catenin mechanosensitivity in the clutch between E-cadherin and cortical F-actin allows cells to interpret the direction of motion via cortical flows and signal for contact to inhibit locomotion.

}, issn = {1878-1551}, doi = {10.1016/j.devcel.2023.06.011}, author = {Noordstra, Ivar and Hermoso, Mario D{\'\i}ez and Schimmel, Lilian and Bonfim-Melo, Alexis and Currin-Ross, Denni and Duong, Cao Nguyen and Kalappurakkal, Joseph Mathew and Morris, Richard G and Vestweber, Dietmar and Mayor, Satyajit and Gordon, Emma and Roca-Cusachs, Pere and Yap, Alpha S} } @article {129160, title = {Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies.}, journal = {Mol Ther Nucleic Acids}, volume = {32}, year = {2023}, month = {2023 Jun 13}, pages = {671-688}, abstract = {

Reactivation of fetal hemoglobin (HbF) is a commonly adapted strategy to ameliorate β-hemoglobinopathies. However, the continued production of defective adult hemoglobin (HbA) limits HbF tetramer production affecting the therapeutic benefits. Here, we evaluated deletional hereditary persistence of fetal hemoglobin (HPFH) mutations and identified an 11-kb sequence, encompassing putative repressor region (PRR) to β-globin exon-1 (βE1), as the core deletion that ablates HbA and exhibits superior HbF production compared with HPFH or other well-established targets. PRR-βE1-edited hematopoietic stem and progenitor cells (HSPCs) retained their genome integrity and their engraftment potential to repopulate for long-term hematopoiesis in immunocompromised mice producing HbF positive cells . Furthermore, PRR-βE1 gene editing is feasible without HSPC culture. Importantly, the editing induced therapeutically significant levels of HbF to reverse the phenotypes of both sickle cell disease and β-thalassemia major. These findings imply that PRR-βE1 gene editing of patient HSPCs could lead to improved therapeutic outcomes for β-hemoglobinopathy gene therapy.

}, issn = {2162-2531}, doi = {10.1016/j.omtn.2023.04.024}, author = {Venkatesan, Vigneshwaran and Christopher, Abisha Crystal and Rhiel, Manuel and Azhagiri, Manoj Kumar K and Babu, Prathibha and Walavalkar, Kaivalya and Saravanan, Bharath and Andrieux, Geoffroy and Rangaraj, Sumathi and Srinivasan, Saranya and Karuppusamy, Karthik V and Jacob, Annlin and Bagchi, Abhirup and Pai, Aswin Anand and Nakamura, Yukio and Kurita, Ryo and Balasubramanian, Poonkuzhali and Pai, Rekha and Marepally, Srujan Kumar and Mohankumar, Kumarasamypet Murugesan and Velayudhan, Shaji R and Boerries, Melanie and Notani, Dimple and Cathomen, Toni and Srivastava, Alok and Thangavel, Saravanabhavan} } @article {118724, title = {Effect of hybrid immunity, school reopening, and the Omicron variant on trajectory of COVID-19 epidemic in India: A modelling study.}, journal = {Lancet Reg Health Southeast Asia}, year = {2023}, month = {2022 Oct 13}, pages = {100095}, abstract = {

Background: The course of the COVID-19 pandemic has been driven by several dynamic behavioral, immunological, and viral factors. We used mathematical modeling to explore how the concurrent reopening of schools, increasing levels of hybrid immunity, and the emergence of the Omicron variant affected the trajectory of the pandemic in India, using Andhra Pradesh (pop: 53 million) as an exemplar Indian state.

Methods: We constructed an age- and contact-structured compartmental model that allows for individuals to proceed through various states depending on whether they have received zero, one, or two doses of the COVID-19 vaccine. We calibrated our model using results from another model (ie, INDSCI-SIM) as well as available context-specific serosurvey data. The introduction of the Omicron variant is modelled alongside protection gained from hybrid immunity. We predict disease dynamics in the background of hybrid immunity coming from infections and an ongoing vaccination program, given prior levels of seropositivity from earlier waves of infection. We describe the consequences of school reopening on cases across different age-bands, as well as the impact of the Omicron (BA.2) variant.

Findings: We show the existence of an epidemic peak in India that is strongly related to the value of background seroprevalence. As expected, because children were not vaccinated in India, re-opening schools increases the number of cases in children more than in adults, although in all scenarios, the peak number of active hospitalizations was never greater than 0.45 times the corresponding peak in the Delta wave before schools were reopened. We varied the level of infection induced seropositivity in our model and found the height of the peak associated with schools reopening reduced as background infection-induced seropositivity increased from 20\% to 40\%. At reported values of seropositivity of 64\% from representative surveys done in India, no discernable peak was observed. We also explored counterfactual scenarios regarding the effect of vaccination on hybrid immunity. We found that in the absence of vaccination, even at high levels of seroprevalence (\>60\%), the emergence of the Omicron variant would have resulted in a large rise in cases across all age bands by as much as 1.8 times. We conclude that the presence of high levels of hybrid immunity resulted in fewer cases in the Omicron wave than in the Delta wave.

Interpretation: In India, decreasing prevalence of immunologically na{\"\i}ve individuals of all ages was associated with fewer cases reported once schools were reopened. In addition, hybrid immunity, together with the lower intrinsic severity of disease associated with the Omicron variant, contributed to low reported COVID-19 hospitalizations and deaths.

Funding: World Health Organization, Mphasis.

}, issn = {2772-3682}, doi = {10.1016/j.lansea.2022.100095}, author = {Mozaffer, Farhina and Cherian, Philip and Krishna, Sandeep and Wahl, Brian and Menon, Gautam I} } @article {125198, title = {Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity.}, journal = {Front Mol Biosci}, volume = {10}, year = {2023}, month = {2023}, pages = {1021733}, abstract = {

Kinetic stability, defined as the rate of protein unfolding, is central to determining the functional lifetime of proteins, both in nature and in wide-ranging medical and biotechnological applications. Further, high kinetic stability is generally correlated with high resistance against chemical and thermal denaturation, as well as proteolytic degradation. Despite its significance, specific mechanisms governing kinetic stability remain largely unknown, and few studies address the rational design of kinetic stability. Here, we describe a method for designing protein kinetic stability that uses protein long-range order, absolute contact order, and simulated free energy barriers of unfolding to quantitatively analyze and predict unfolding kinetics. We analyze two β-trefoil proteins: hisactophilin, a quasi-three-fold symmetric natural protein with moderate stability, and ThreeFoil, a designed three-fold symmetric protein with extremely high kinetic stability. The quantitative analysis identifies marked differences in long-range interactions across the protein hydrophobic cores that partially account for the differences in kinetic stability. Swapping the core interactions of ThreeFoil into hisactophilin increases kinetic stability with close agreement between predicted and experimentally measured unfolding rates. These results demonstrate the predictive power of readily applied measures of protein topology for altering kinetic stability and recommend core engineering as a tractable target for rationally designing kinetic stability that may be widely applicable.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2023.1021733}, author = {Anderson, Delaney M and Jayanthi, Lakshmi P and Gosavi, Shachi and Meiering, Elizabeth M} } @article {126681, title = {Environmental heterogeneity modulates the effect of plant diversity on the spatial variability of grassland biomass.}, journal = {Nat Commun}, volume = {14}, year = {2023}, month = {2023 Mar 31}, pages = {1809}, abstract = {

Plant productivity varies due to environmental heterogeneity, and theory suggests that plant diversity can reduce this variation. While there is strong evidence of diversity effects on temporal variability of productivity, whether this mechanism extends to variability across space remains elusive. Here we determine the relationship between plant diversity and spatial variability of productivity in 83 grasslands, and quantify the effect of experimentally increased spatial heterogeneity in environmental conditions on this relationship. We found that communities with higher plant species richness (alpha and gamma diversity) have lower spatial variability of productivity as reduced abundance of some species can be compensated for by increased abundance of other species. In contrast, high species dissimilarity among local communities (beta diversity) is positively associated with spatial variability of productivity, suggesting that changes in species composition can scale up to affect productivity. Experimentally increased spatial environmental heterogeneity weakens the effect of plant alpha and gamma diversity, and reveals that beta diversity can simultaneously decrease and increase spatial variability of productivity. Our findings unveil the generality of the diversity-stability theory across space, and suggest that reduced local diversity and biotic homogenization can affect the spatial reliability of key ecosystem functions.

}, keywords = {Biodiversity, Biomass, Ecosystem, Grassland, Plants, Reproducibility of Results}, issn = {2041-1723}, doi = {10.1038/s41467-023-37395-y}, author = {Daleo, Pedro and Alberti, Juan and Chaneton, Enrique J and Iribarne, Oscar and Tognetti, Pedro M and Bakker, Jonathan D and Borer, Elizabeth T and Bruschetti, Mart{\'\i}n and MacDougall, Andrew S and Pascual, Jesus and Sankaran, Mahesh and Seabloom, Eric W and Wang, Shaopeng and Bagchi, Sumanta and Brudvig, Lars A and Catford, Jane A and Dickman, Chris R and Dickson, Timothy L and Donohue, Ian and Eisenhauer, Nico and Gruner, Daniel S and Haider, Sylvia and Jentsch, Anke and Knops, Johannes M H and Lekberg, Ylva and McCulley, Rebecca L and Moore, Joslin L and Mortensen, Brent and Ohlert, Timothy and P{\"a}rtel, Meelis and Peri, Pablo L and Power, Sally A and Risch, Anita C and Rocca, Camila and Smith, Nicholas G and Stevens, Carly and Tamme, Riin and Veen, G F Ciska and Wilfahrt, Peter A and Hautier, Yann} } @article {123124, title = {ER-Ca2+ stores and the regulation of Store-operated Ca2+ Entry in neurons.}, journal = {J Physiol}, year = {2023}, month = {2023 Jan 24}, abstract = {

Key components of endoplasmic reticular (ER) Ca release and store-operated Ca entry (SOCE) are likely expressed in all metazoan cells. Due to the complexity of canonical Ca entry mechanisms in neurons, the functional significance of ER-Ca release and SOCE has been difficult to identify and establish. In this review we present evidence of how these two related mechanisms of Ca signaling impact multiple aspects of neuronal physiology and discuss their interaction with the better understood classes of ion channels that are gated by either voltage changes or extracellular ligands in neurons. Given how a small imbalance in Ca homeostasis can have strongly detrimental effects on neurons, leading to cell death, it is essential that neuronal SOCE is carefully regulated. We go onto discuss mechanisms of SOCE regulation identified in Drosophila and mammalian neurons. These include specific splice variants of STIM, different classes of membrane interacting proteins and an ER-Ca channel. So far these appear distinct from the mechanisms of SOCE regulation identified in non-excitable cells. Finally we touch upon the significance of these studies in the context of certain human neurodegenerative diseases. Abstract figure legend Store-operated Ca entry in neuronal cells is regulated by both positive (left) and negative regulators (right). This article is protected by copyright. All rights reserved.

}, issn = {1469-7793}, doi = {10.1113/JP283827}, author = {Chakraborty, Pragnya and Hasan, Gaiti} } @article {130542, title = {The evolution and ecology of multiple antipredator defences.}, journal = {J Evol Biol}, year = {2023}, month = {2023 Jun 26}, abstract = {

Prey seldom rely on a single type of antipredator defence, often using multiple defences to avoid predation. In many cases, selection in different contexts may favour the evolution of multiple defences in a prey. However, a prey may use multiple defences to protect itself during a single predator encounter. Such "defence portfolios" that defend prey against a single instance of predation are distributed across and within successive stages of the predation sequence (encounter, detection, identification, approach (attack), subjugation and consumption). We contend that at present, our understanding of defence portfolio evolution is incomplete, and seen from the fragmentary perspective of specific sensory systems (e.g., visual) or specific types of defences (especially aposematism). In this review, we aim to build a comprehensive framework for conceptualizing the evolution of multiple prey defences, beginning with hypotheses for the evolution of multiple defences in general, and defence portfolios in particular. We then examine idealized models of resource trade-offs and functional interactions between traits, along with evidence supporting them. We find that defence portfolios are constrained by resource allocation to other aspects of life history, as well as functional incompatibilities between different defences. We also find that selection is likely to favour combinations of defences that have synergistic effects on predator behaviour and prey survival. Next, we examine specific aspects of prey ecology, genetics and development, and predator cognition that modify the predictions of current hypotheses or introduce competing hypotheses. We outline schema for gathering data on the distribution of prey defences across species and geography, determining how multiple defences are produced, and testing the proximate mechanisms by which multiple prey defences impact predator behaviour. Adopting these approaches will strengthen our understanding of multiple defensive strategies.

}, issn = {1420-9101}, doi = {10.1111/jeb.14192}, author = {Kikuchi, David W and Allen, William L and Arbuckle, Kevin and Aubier, Thomas G and Briolat, Emmanuelle S and Burdfield-Steel, Emily R and Cheney, Karen L and Da{\v n}kov{\'a}, Kl{\'a}ra and Elias, Marianne and H{\"a}m{\"a}l{\"a}inen, Liisa and Herberstein, Marie E and Hossie, Thomas J and Joron, Mathieu and Kunte, Krushnamegh and Leavell, Brian C and Lindstedt, Carita and Lorioux-Chevalier, Ugo and McClure, Melanie and McLellan, Callum F and Medina, Iliana and Nawge, Viraj and P{\'a}ez, Erika and Pal, Arka and Pek{\'a}r, Stano and Penacchio, Olivier and Ra{\v s}ka, Jan and Reader, Tom and Rojas, Bibiana and R{\"o}nk{\"a}, Katja H and R{\"o}{\ss}ler, Daniela C and Rowe, Candy and Rowland, Hannah M and Roy, Arlety and Schaal, Kaitlin A and Sherratt, Thomas N and Skelhorn, John and Smart, Hannah R and Stankowich, Ted and Stefan, Amanda M and Summers, Kyle and Taylor, Christopher H and Thorogood, Rose and Umbers, Kate and Winters, Anne E and Yeager, Justin and Exnerov{\'a}, Alice} } @article {126683, title = {Evolutionary dynamics of dengue virus in India.}, journal = {PLoS Pathog}, volume = {19}, year = {2023}, month = {2023 Apr 03}, pages = {e1010862}, abstract = {

More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country{\textquoteright}s population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country. Here, we present a comprehensive analysis of all DENV gene sequences collected between 1956 and 2018 from India. We examine the spatio-temporal dynamics of India-specific genotypes, their evolutionary relationship with global and local dengue virus strains, interserotype dynamics and their divergence from the vaccine strains. Our analysis highlights the co-circulation of all DENV serotypes in India with cyclical outbreaks every 3-4 years. Since 2000, genotype III of DENV-1, cosmopolitan genotype of DENV-2, genotype III of DENV-3 and genotype I of DENV-4 have been dominating across the country. Substitution rates are comparable across the serotypes, suggesting a lack of serotype-specific evolutionary divergence. Yet, the envelope (E) protein displays strong signatures of evolution under immune selection. Apart from drifting away from its ancestors and other contemporary serotypes in general, we find evidence for recurring interserotype drift towards each other, suggesting selection via cross-reactive antibody-dependent enhancement. We identify the emergence of the highly divergent DENV-4-Id lineage in South India, which has acquired half of all E gene mutations in the antigenic sites. Moreover, the DENV-4-Id is drifting towards DENV-1 and DENV-3 clades, suggesting the role of cross-reactive antibodies in its evolution. Due to the regional restriction of the Indian genotypes and immunity-driven virus evolution in the country, ~50\% of all E gene differences with the current vaccines are focused on the antigenic sites. Our study shows how the dengue virus evolution in India is being shaped in complex ways.

}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1010862}, author = {Jagtap, Suraj and Pattabiraman, Chitra and Sankaradoss, Arun and Krishna, Sudhir and Roy, Rahul} } @article {123070, title = {Fitness landscapes reveal context-dependent benefits of oviposition behavior.}, journal = {Evolution}, volume = {77}, year = {2023}, month = {2022 Dec 08}, pages = {550-561}, abstract = {

Resource choice behavior has enormous fitness consequences and can drive niche expansion. However, individual behavioral choices are often mediated by context, determined by past experience. Do such context-dependent behaviors reflect maladaptive variation or are they locally adaptive? Using Tribolium castaneum (the red flour beetle), we demonstrate that context-dependent oviposition behavior reflects distinct, context-specific local fitness peaks. We measured offspring fitness to generate fitness landscapes as a function of all possible oviposition behaviors (i.e., combinations of fecundity and resource preference) in a habitat containing optimal and suboptimal resource patches. We did this by experimentally manipulating egg allocation across patches, which allowed us to assess behaviors not typically observed in the laboratory. We found that females from different age and competition contexts exhibit distinct behaviors which optimize different fitness components, linked in a tradeoff. With prior exposure to strong competition and increasing age, females produce few but fast-developing offspring that are advantageous under high resource competition. In contrast, young na{\"\i}ve females produce significantly more (but slower developing) offspring, which is beneficial under weak competition. Systematically mapping complete context-dependent fitness landscapes is thus critical to infer behavioral optimality and offers predictive power in novel contexts.

}, issn = {1558-5646}, doi = {10.1093/evolut/qpac035}, author = {Ravi Kumar, Vrinda and Agavekar, Gaurav and Agashe, Deepa} } @article {120169, title = {Functional analysis of structural variants in single cells using Strand-seq.}, journal = {Nat Biotechnol}, volume = {41}, year = {2023}, month = {2022 Nov 24}, pages = {832-844}, chapter = {6}, abstract = {

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations.

}, issn = {1546-1696}, doi = {10.1038/s41587-022-01551-4}, author = {Jeong, Hyobin and Grimes, Karen and Rauwolf, Kerstin K and Bruch, Peter-Martin and Rausch, Tobias and Hasenfeld, Patrick and Benito, Eva and Roider, Tobias and Sabarinathan, Radhakrishnan and Porubsky, David and Herbst, Sophie A and Erarslan-Uysal, B{\"u}{\c s}ra and Jann, Johann-Christoph and Marschall, Tobias and Nowak, Daniel and Bourquin, Jean-Pierre and Kulozik, Andreas E and Dietrich, Sascha and Bornhauser, Beat and Sanders, Ashley D and Korbel, Jan O} } @article {129167, title = {Gene flow drives genomic diversity in Asian Pikas distributed along the core and range-edge habitats in the Himalayas.}, journal = {Ecol Evol}, volume = {13}, year = {2023}, month = {2023 May}, pages = {e10129}, abstract = {

Studying the genetic variation among different species distributed across their core and range-edge habitats can provide valuable insights into how genetic variation changes across the species{\textquoteright} distribution range. This information can be important for understanding local adaptation, as well as for conservation and management efforts. In this study, we have carried out genomic characterization of six species of Asian Pikas distributed along their core and range-edge habitats in the Himalayas. We utilized a population genomics approach using ~28,000 genome-wide SNP markers obtained from restriction-site associated DNA sequencing. We identified low nucleotide diversity and high inbreeding coefficients in all six species across their core and range-edge habitats. We also identified evidence of gene flow among genetically diverse species. Our results provide evidence of reduced genetic diversity in Asian pikas distributed across the Himalayas and the neighboring regions and indicate that recurrent gene flow is possibly a key mechanism for maintaining genetic diversity and adaptive potential in these pikas. However, full-scale genomics studies that utilize whole-genome sequencing approaches will be needed to quantify the direction and timing of gene flow and functional changes associated with introgressed regions in the genome. Our results represent an important step toward understanding the patterns and consequences of gene flow in species, sampled at the least studied, yet climatically vulnerable part of their habitat that can be further used to inform conservation strategies that promote connectivity and gene flow between populations.

}, issn = {2045-7758}, doi = {10.1002/ece3.10129}, author = {Dahal, Nishma and Romine, Melia G and Khatiwara, Sunita and Ramakrishnan, Uma and Lamichhaney, Sangeet} } @article {124444, title = {Generation of feeder-independent transgene-free iPSC lines from a young-onset Parkinson{\textquoteright}s disease (YOPD) patient with a homozygous PLA2G6: c.2222G>A (p. Arg741Gln) mutation (NCBSi003-A) and unaffected heterozygous parent (NCBSi004-A).}, journal = {Stem Cell Res}, volume = {67}, year = {2023}, month = {2023 Jan 24}, pages = {103033}, abstract = {

Phospholipase A2 group 6 (PLA2G6, iPLA2β or PARK14) gene encodes a calcium-independent group 6 phospholipase A2 enzyme and is associated with young-onset autosomal recessive Parkinson{\textquoteright}s disease (PD). We generated human induced pluripotent stem cell (iPSC) lines from a patient with young-onset PD carrying a homozygous PLA2G6: c.2222G\>A (p. Arg741Gln) mutation (NCBSi003-A) and unaffected heterozygous parent (NCBSi004-A). These iPSC lines will be used for investigating the key molecular signatures of young-onset PD (YOPD), and to understand the predictive phenotypes of the disease.

}, issn = {1876-7753}, doi = {10.1016/j.scr.2023.103033}, author = {Gopurappilly, Renjitha and Musthafa, Thasneem and Sukumaran, Salil and Viswanath, Biju and Hasan, Gaiti} } @article {129157, title = {A geometrical perspective on development.}, journal = {Dev Growth Differ}, year = {2023}, month = {2023 May 16}, abstract = {

Cell fate decisions emerge as a consequence of a complex set of gene regulatory networks. Models of these networks are known to have more parameters than data can determine. Recent work, inspired by Waddington{\textquoteright}s metaphor of a landscape, has instead tried to understand the geometry of gene regulatory networks. Here, we describe recent results on the appropriate mathematical framework for constructing these landscapes. This allows the construction of minimally parameterized models consistent with cell behavior. We review existing examples where geometrical models have been used to fit experimental data on cell fate and describe how spatial interactions between cells can be understood geometrically.

}, issn = {1440-169X}, doi = {10.1111/dgd.12855}, author = {Raju, Archishman and Siggia, Eric D} } @article {129156, title = {A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins.}, journal = {Nat Ecol Evol}, year = {2023}, month = {2023 May 15}, abstract = {

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92\% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.

}, issn = {2397-334X}, doi = {10.1038/s41559-023-02041-9}, author = {Kawahara, Akito Y and Storer, Caroline and Carvalho, Ana Paula S and Plotkin, David M and Condamine, Fabien L and Braga, Mariana P and Ellis, Emily A and St Laurent, Ryan A and Li, Xuankun and Barve, Vijay and Cai, Liming and Earl, Chandra and Frandsen, Paul B and Owens, Hannah L and Valencia-Montoya, Wendy A and Aduse-Poku, Kwaku and Toussaint, Emmanuel F A and Dexter, Kelly M and Doleck, Tenzing and Markee, Amanda and Messcher, Rebeccah and Nguyen, Y-Lan and Badon, Jade Aster T and Ben{\'\i}tez, Hugo A and Braby, Michael F and Buenavente, Perry A C and Chan, Wei-Ping and Collins, Steve C and Rabideau Childers, Richard A and Dankowicz, Even and Eastwood, Rod and Fric, Zdenek F and Gott, Riley J and Hall, Jason P W and Hallwachs, Winnie and Hardy, Nate B and Sipe, Rachel L Hawkins and Heath, Alan and Hinolan, Jomar D and Homziak, Nicholas T and Hsu, Yu-Feng and Inayoshi, Yutaka and Itliong, Micael G A and Janzen, Daniel H and Kitching, Ian J and Kunte, Krushnamegh and Lamas, Gerardo and Landis, Michael J and Larsen, Elise A and Larsen, Torben B and Leong, Jing V and Lukhtanov, Vladimir and Maier, Crystal A and Martinez, Jose I and Martins, Dino J and Maruyama, Kiyoshi and Maunsell, Sarah C and Mega, Nicol{\'a}s Oliveira and Monastyrskii, Alexander and Morais, Ana B B and M{\"u}ller, Chris J and Naive, Mark Arcebal K and Nielsen, Gregory and Padr{\'o}n, Pablo Sebasti{\'a}n and Peggie, Djunijanti and Romanowski, Helena Piccoli and S{\'a}fi{\'a}n, Szabolcs and Saito, Motoki and Schr{\"o}der, Stefan and Shirey, Vaughn and Soltis, Doug and Soltis, Pamela and Sourakov, Andrei and Talavera, Gerard and Vila, Roger and Vlasanek, Petr and Wang, Houshuai and Warren, Andrew D and Willmott, Keith R and Yago, Masaya and Jetz, Walter and Jarzyna, Marta A and Breinholt, Jesse W and Espeland, Marianne and Ries, Leslie and Guralnick, Robert P and Pierce, Naomi E and Lohman, David J} } @article {131924, title = {Hemidactylus paucifasciatus (Squamata: Gekkonidae), a new species of large-bodied, tuberculate gecko from Northern Odisha, India}, journal = {ZOOTAXA }, volume = {5301}, year = {2023}, month = {06/2023}, pages = {365-382}, abstract = {

A new Hemidactylus belonging to the H. prashadi group is described herein, based on a series of four specimens from the Chota Nagpur Plateau in northern Odisha. Hemidactylus paucifasciatus sp. nov. can be diagnosed from regional congeners by its large body size (SVL up to 117.7 mm), the number of dorsal tubercle rows at mid-body, three or four bands on the dorsum, the number of enlarged tubercles in paravertebral rows, the number of femoral pores and poreless scales separating the left and right series on the femoral-precloacal row in males, and the number of ventral scales across the belly at mid-body. A mitochondrial phylogeny demonstrates that the new species is nested within the H. triedrus complex of the northern clade within the H. prashadi group, with 16.2-16.5 \% pairwise divergence in ND2 sequence data from members of the H. triedrus complex and \> 21 \% from other members of the prashadi group. Hemidactylus paucifasciatus sp. nov. is the first endemic gecko to be described from the Chota Nagpur Plateau.

}, doi = {10.11646/zootaxa.5301.3.3}, author = {Mohapatra, Pratyush P. and Agarwal, Ishan and Mohalik, Rakesh Kumar and Dutta, Sushil K. and Khandekar, Akshay} } @article {126687, title = {High-quality single amplicon sequencing method for illumina MiSeq platform using pool of {\textquoteright}N{\textquoteright} (0-10) spacer-linked target specific primers without PhiX spike-in.}, journal = {BMC Genomics}, volume = {24}, year = {2023}, month = {2023 Mar 23}, pages = {141}, abstract = {

BACKGROUND: Illumina sequencing platform requires base diversity in the initial 11 cycles for efficient cluster identification and colour matrix estimation. This limitation yields low-quality data for amplicon libraries having homogeneous base composition. Spike-in of PhiX library ensures base diversity but reduces the overall number of sequencing reads for data analysis. To overcome such low diversity issues during amplicon sequencing on illumina platforms, we developed a high throughput single amplicon sequencing method by introducing {\textquoteright}N{\textquoteright} (0-10) spacers in target gene amplification primers that are pooled for simple handling.

RESULT: We evaluated the efficiency of {\textquoteright}N{\textquoteright} (0-10) spacer-linked primers by targeting bacterial 16S V3-V4 region, demonstrating heterogeneous base library construction. The addition of {\textquoteright}N{\textquoteright} (0-10) spacers causes sequencing frameshift at every base that leads to base diversity and produces heterogeneous high quality reads within a single amplicon library. We have written a python based command-line software,"MetReTrim", to trim the {\textquoteright}N{\textquoteright} (0-10) spacers from the raw reads ( https://github.com/Mohak91/MetReTrim ). We further demonstrated the accuracy of this method by comparative mock community analysis with standard illumina V3-V4 primer method. The ZymoBIOMICS{\texttrademark} microbial community DNA standard was used as a control for this study. We performed data analysisusing the DADA2 pipeline where taxonomy was assigned using SILVA database as reference. We observed no difference between the communities represented by our method and standard illumina V3-V4 primer method.

CONCLUSION: This method eliminates the need for PhiX spike-in for single amplicon sequencing on illumina MiSeq platform. This allows for sequencing of more number of samples in a run and a reduction in the overall cost. Given that Illumina sequencing works on SBS chemistry irrespective of the platform (such as HiSeq, MiSeq, NextSeq, NovaSeq, etc.) we propose that this strategy of using {\textquoteright}N{\textquoteright} (0-10) spacer-linked primer design can be adopted for generating high-quality single locus amplicon sequencing in a high throughput manner across the illumina platform subject to further validation.

}, keywords = {Bacteria, Gene Library, High-Throughput Nucleotide Sequencing, Microbiota, RNA, Ribosomal, 16S, Sequence Analysis, DNA}, issn = {1471-2164}, doi = {10.1186/s12864-023-09233-4}, author = {Naik, Tejali and Sharda, Mohak and C P, Lakshminarayanan and Virbhadra, Kumar and Pandit, Awadhesh} } @article {135856, title = {How India Changed My Ideas About Honey Bees}, journal = {JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE }, year = {2023}, month = {10/2023}, abstract = {

Research on honey bees, one of the most famous social insects, has been largely limited to studies on Central European populations of the Western honey bee, Apis mellifera. Most researchers view the biology and social organization of this phylogenetically derived species as the blueprint for all honey bees, although there is accumulating evidence that several important characters are unique physiological or evolutionary adaptations to living in a temperate climate. The review presents a personal (re)collection of research efforts, ideas, and opinions on the neglected Asian honey bees. There are two major take-home messages: (1) it is of utmost importance that India and other tropical Asian countries increase their research efforts to study and conserve honey bees and other insect pollinators to sustain biodiversity and human nutritional demands, and (2) the study of the behavior of the phylogenetically ancestral Asian honey bees will provide us with a profound understanding of the structure and flexibility in the social organization of honey bees.

}, doi = {10.1007/s41745-023-00412-6}, author = {Brockmann, A} } @article {137334, title = {On the identity of Hesperia parrhasius Fabricius, 1793 and its allied species (Lepidoptera: Lycaenidae)}, journal = {JOURNAL OF ASIA-PACIFIC ENTOMOLOGY }, volume = {26}, year = {2023}, month = {12/2023}, pages = {102165}, abstract = {

In light of new evidence from DNA and morphology of male genitalia, we review and clarify the status of nominal lycaenid taxa Hesperia parrhasius Fabricius 1793, Lycaena pandava Horsfield [1829], L. contracta Butler 1880 and Catochrysops ella Butler 1881. We designate a neotype for H. parrhasius and a lectotype for C. bengalia de Nice {\textquoteright} ville, 1885. The following new combinations, status and synonymies are established: Lachides galba (Lederer, 1855) = Lycaena phiala Grum-Grshimailo, 1890, syn. nov.; Lachides parrhasius contracta (Butler, 1880), stat. nov. = Catochrysops ella Butler 1881, syn. nov.; Lachides parrhasius nila (Evans, 1925), comb. nov.; Luthrodes pandava (Horsfiled, [1828]) = Cathochrysops bengalia de Nice {\textquoteright} ville, 1885, syn. nov. and Luthrodes pandava (Horsfield, [1829]) = Lycaenesthes orissica Moore, 1884, syn. nov. A checklist with all taxonomic changes to the discussed taxa is provided.

}, doi = {10.1016/j.aspen.2023.102165}, author = {Nazari, Vazrick and Kunte, Krushnamegh and Balint, Zsolt} } @article {134610, title = {An improved rhythmicity analysis method using Gaussian Processes detects cell-density dependent circadian oscillations in stem cells.}, journal = {Bioinformatics}, year = {2023}, month = {2023 Sep 28}, abstract = {

MOTIVATION: Detecting oscillations in time series remains a challenging problem even after decades of research. In chronobiology, rhythms (for instance in gene expression, eclosion, egg-laying and feeding) tend to be low amplitude, display large variations amongst replicates, and often exhibit varying peak-to-peak distances (non-stationarity). Most currently available rhythm detection methods are not specifically designed to handle such datasets, and are also limited by their use of p-values in detecting oscillations.

RESULTS: We introduce a new method, ODeGP (Oscillation Detection using Gaussian Processes), which combines Gaussian Process (GP) regression and Bayesian inference to incorporate measurement errors, non-uniformly sampled data, and a recently developed non-stationary kernel to improve detection of oscillations. By using Bayes factors, ODeGP models both the null (non-rhythmic) and the alternative (rhythmic) hypotheses, thus providing an advantage over p-values. Using synthetic datasets we first demonstrate that ODeGP almost always outperforms eight commonly used methods in detecting stationary as well as non-stationary symmetric oscillations. Next, by analyzing existing qPCR datasets we demonstrate that our method is more sensitive compared to the existing methods at detecting weak and noisy oscillations. Finally, we generate new qPCR data on mouse embryonic stem cells. Surprisingly, we discover using ODeGP that increasing cell density results in rapid generation of oscillations in the Bmal1 gene, thus highlighting our method{\textquoteright}s ability to discover unexpected and new patterns. In its current implementation, ODeGP is meant only for analyzing single or a few time-trajectories, not genome-wide datasets.

AVAILABILITY AND IMPLEMENTATION: ODeGP is available at https://github.com/Shaonlab/ODeGP.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Journal Name online.

}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btad602}, author = {Sahay, Shabnam and Adhikari, Shishir and Hormoz, Sahand and Chakrabarti, Shaon} } @article {125201, title = {Indian Himalayan natural Arabidopsis thaliana accessions with abolished miR158 levels exhibit robust miR173-initiated trans-acting cascade silencing.}, journal = {Plant J}, year = {2023}, month = {2023 Mar 08}, abstract = {

Small RNAs such as microRNAs (miRNAs) and small interfering (si)RNAs are short 20-24-nucleotide non-coding RNAs. They are key regulators of gene expression in plants and other organisms. Several 22-nucleotide long miRNAs trigger biogenesis of cascades of trans-acting secondary small interfering RNAs, involved in various developmental and stress responses. Here we show that in Himalayan Arabidopsis thaliana accessions having natural mutations in miR158 locus exhibit robust cascade silencing in pentatricopeptide (PPR)-like locus. Furthermore, we show that these cascade sRNAs trigger tertiary silencing of a gene involved in transpiration and stomatal opening. The natural variants of MIR158 having deletions or insertions led to improper processing of miR158 precursors thereby blocking synthesis of mature miR158. Reduced miR158 led to increased level of its target, a pseudo-pentatricopeptide gene that is otherwise targeted by ta-siRNAs generated by miR173 cascade in other accessions. Using small RNA datasets derived from Indian Himalayan accessions, as well as overexpression and knockout lines of miR158, we show that absence of miR158 led to build up of pseudo-PPR derived tertiary small RNAs. These tertiary sRNAs mediated robust silencing of a gene involved in stomatal closure in Himalayan accessions lacking miR158 expression. We functionally validated the tertiary phasiRNA that targets NHX2 a Na -K /H antiporter protein thereby regulating transpiration and stomatal conductance. Overall, we deciphered a new module of sRNA network, miRNA-TAS-siRNA-pseudogene-tertiary phasiRNA-NHX2 in plant adaptation.

}, issn = {1365-313X}, doi = {10.1111/tpj.16175}, author = {Tripathi, Abhinandan Mani and Singh, Rajneesh and Verma, Ashwani Kumar and Singh, Akanksha and Mishra, Parneeta and Dwivedi, Varun and Narayan, Shiv and Sundar, G Vivek Hari and Shirke, Pramod Arvind and Shivaprasad, P V and Roy, Sribash} } @article {130540, title = {Influence of pH on indole-dependent heterodimeric interactions between Anopheles gambiae odorant-binding proteins OBP1 and OBP4.}, journal = {Int J Biol Macromol}, year = {2023}, month = {2023 Jun 15}, pages = {125422}, abstract = {

Insect Odorant Binding Proteins (OBPs) constitute important components of their olfactory apparatus, as they are essential for odor recognition. OBPs undergo conformational changes upon pH change, altering their interactions with odorants. Moreover, they can form heterodimers with novel binding characteristics. Anopheles gambiae OBP1 and OBP4 were found capable of forming heterodimers possibly involved in the specific perception of the attractant indole. In order to understand how these OBPs interact in the presence of indole and to investigate the likelihood of a pH-dependent heterodimerization mechanism, the crystal structures of OBP4 at pH 4.6 and 8.5 were determined. Structural comparison to each other and with the OBP4-indole complex (3Q8I, pH 6.85) revealed a flexible N-terminus and conformational changes in the α4-loop-α5 region at acidic pH. Fluorescence competition assays showed a weak binding of indole to OBP4 that become further impaired at acidic pH. Additional Molecular Dynamic and Differential Scanning Calorimetry studies displayed that the influence of pH on OBP4 stability is significant compared to the modest effect of indole. Furthermore, OBP1-OBP4 heterodimeric models were generated at pH 4.5, 6.5, and 8.5, and compared concerning their interface energy and cross-correlated motions in the absence and presence of indole. The results indicate that the increase in pH may induce the stabilization of OBP4 by increasing its helicity, thereby enabling indole binding at neutral pH that further stabilizes the protein and possibly promotes the creation of a binding site for OBP1. A decrease in interface stability and loss of correlated motions upon transition to acidic pH may provoke the heterodimeric dissociation allowing indole release. Finally, we propose a potential OBP1-OBP4 heterodimer formation/disruption mechanism induced by pH change and indole binding.

}, issn = {1879-0003}, doi = {10.1016/j.ijbiomac.2023.125422}, author = {Mam, Bhavika and Tsitsanou, Katerina E and Liggri, Panagiota G V and Saitta, Francesca and Stamati, Evgenia C V and Mahita, Jarjapu and Leonis, George and Drakou, Christina E and Papadopoulos, Manthos and Arnaud, Philippe and Offmann, Bernard and Fessas, Dimitrios and Sowdhamini, Ramanathan and Zographos, Spyros E} } @article {133176, title = {Integrated approaches for the recognition of small molecule inhibitors for Toll-like receptor 4.}, journal = {Comput Struct Biotechnol J}, volume = {21}, year = {2023}, month = {2023}, pages = {3680-3689}, abstract = {

Toll-like receptors (TLRs) are pattern recognition receptors present on the surface of cells playing a crucial role in innate immunity. One of the TLRs, TLR4, recognizes LPS (Lipopolysaccharide) as its ligand leading to the release of anti-inflammatory mediators as well as pro-inflammatory cytokines through signal transduction and domain recruitment. TLR4 homodimerizes at its intracellular TIR (Toll/interleukin-1 receptor) domain that helps in the recruitment of the TRAM/TICAM2 (TIR domain-containing adaptor molecule 2) molecule. TRAM also contains TIR domain which in turn, dimerizes and functions as an adapter protein to further recruit TRIF/TICAM1 (TIR domain-containing adaptor molecule 1) protein for mediating downstream signaling. Apart from LPS, TLR4 also recognizes endogenous ligands like fibrinogen, HMGB1, and hyaluronan in autoimmune conditions and sepsis. We employed computational approaches to target TRAM and recognize small molecule inhibitors from small molecules of natural origin, as contained in the Super Natural II database. Finally, cell reporter assays and NMR studies enabled the identification of promising lead compounds. Hence, this study aims to attenuate the signaling of the TLR4-TRAM-TRIF cascade in these auto-inflammatory conditions.

}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.07.026}, author = {Verma, Shailya and Reddy, Purushotham and Sowdhamini, R} } @article {122347, title = {An interdisciplinary effort to understand chemical organizations at the origin of life.}, journal = {iScience}, volume = {26}, year = {2023}, month = {2023 Jan 20}, pages = {105834}, abstract = {

This backstory features the perspectives of three group leaders of a Franco-Indian collaboration on the origin of life, involving efforts to engineer evolvable chemical systems. The researchers explain how they overcame the difficulties to bring empiricist and theorist cultures together and the importance of such synergy for the future of origin of life research.

}, issn = {2589-0042}, doi = {10.1016/j.isci.2022.105834}, author = {Jeancolas, C and Singh, A Y and Jain, S and Krishna, S and Nghe, P} } @article {126628, title = {Isolation, Functionalization, In Silico Investigation, and Synthesis of 1,8-Cineole Analog as Antitubercular Agent Targeting InhA}, journal = {Russian Journal of Bioorganic Chemistry}, year = {2023}, month = {03/2023}, abstract = {

A desirable and established target for creating antituberculosis drug lead molecules is the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase InhA. Additionally, direct inhibitors of InhA continue to be effective against InhA variants with mutations linked to isoniazid resistance, providing the possibility of activity against MDR isolates. Initially, we isolated monoterpenoid 1,8-cineole from leaf parts of the Callistemon citrinus by aqueous ethanol extract, followed functionalization with several functional groups, and we created a novel 1,8-cineole analogue as a novel compound for treating tuberculosis infection. This study used a structure-based virtual screening of 20 structures to identify novel lead InhA inhibitors as potential antituberculosis drugs. Compound (SG01) was identified as a lead candidate for the synthesis and has been characterized by IR, H-1, C-13 NMR, and mass spectroscopy. Using a microplate Alamar Blue assay method, the compound was also tested for their in vitro antimycobacterial activity against the H37Rv strain. This compound offers a desirable starting point for ligand optimization attempts to find new and potent anti-tuberculosis drugs that target InhA.

}, doi = {10.1134/S1068162023020206}, author = {Sabarees, G. and Gouthaman, S. and Alagarsamy, V. and Velmurugan, V. and Solomon, V. Raja} } @article {128090, title = {Jammed microgel growth medium prepared by flash-solidification of agarose for 3D cell culture and 3D bioprinting.}, journal = {Biomed Mater}, year = {2023}, month = {2023 May 05}, abstract = {

Although cells cultured in 3D platforms are proven to be beneficial for studying cellular behavior in settings similar to their physiological state, due to the ease, convenience, and accessibility, traditional 2D culturing approaches are widely adopted. Jammed microgels are a promising class of biomaterials extensively suited for 3D cell culture, tissue bioengineering, and 3D bioprinting. However, existing protocols for fabricating such microgels either involve complex synthesis steps, long preparation times, or polyelectrolyte hydrogel formulations that sequester ionic elements from the cell growth media. Hence, there is an unmet need for a broadly biocompatible, high-throughput, and easily accessible manufacturing process. We address these demands by introducing a rapid, high-throughput, and remarkably straightforward method to synthesize jammed microgels composed of flash-solidified agarose granules directly prepared in a culture medium of choice. Our jammed growth media are optically transparent, porous, yield stress materials with tunable stiffness and self-healing properties, which makes them ideal for 3D cell culture as well as 3D bioprinting. The charge-neutral and inert nature of agarose make them suitable for culturing various cell types and species, the specific growth media for which do not alter the chemistry of the manufacturing process. Unlike several existing 3D platforms, these microgels are readily compatible with standard techniques such as absorbance-based growth assays, antibiotic selection, RNA extraction, and live cell encapsulation. In effect, we present a versatile, highly accessible, inexpensive, and easily adoptable biomaterial for 3D cell culture and 3D bioprinting. We envision their widespread application not just in routine laboratory settings but also in designing multicellular tissue mimics and dynamic co-culture models of physiological niches.

}, issn = {1748-605X}, doi = {10.1088/1748-605X/acd315}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Bhat, Ramray and Bhattacharjee, Tapomoy} } @article {137337, title = {Land Cover Mapping of Bengaluru{\textquoteright}s Urban and Surrounding Area with Spatiotemporal Open-source Remote Sensing Data}, journal = {SENSORS AND MATERIALS}, volume = {35}, year = {2023}, month = {12/2023}, pages = {3829-3849}, abstract = {

The rapid urbanization observed in Asian tropics has resulted in extensive landscape transformations, giving rise to novel challenges such as conflicts of interest among citizens and threats to biodiversity. To facilitate informed urban management policies, there is a pressing need for contemporary land use and cover maps that provide precise insights into the evolving landscape. In this paper, we present the city of Bengaluru, India (covering an area of 365,879 ha) as a case study. We introduce an open-source-driven pipeline method capable of generating an updated 11-class land cover map at a high resolution of 10 m, achieving a global F1 score of 0.82. Notably, our proposed pipeline represents a pioneering solution that effectively addresses the persistent issue of cloud cover caused by monsoons, enhancing the utility of such maps for urban management, and planning in rapidly evolving regions.

}, doi = {10.18494/SAM4627}, author = {Grison, Sylvain and Siddaganga, Rajath and Singh, Renu and Hegde, Shrihari and Brockmann, Axel and Krishnan, Smitha and Guo, Wei} } @article {125200, title = {The layered costs and benefits of translational redundancy.}, journal = {Elife}, volume = {12}, year = {2023}, month = {2023 Mar 02}, abstract = {

The rate and accuracy of translation hinges upon multiple components - including transfer RNA (tRNA) pools, tRNA modifying enzymes, and rRNA molecules - many of which are redundant in terms of gene copy number or function. It has been hypothesized that the redundancy evolves under selection, driven by its impacts on growth rate. However, we lack empirical measurements of the fitness costs and benefits of redundancy, and we have poor a understanding of how this redundancy is organized across components. We manipulated redundancy in multiple translation components of by deleting 28 tRNA genes, 3 tRNA modifying systems, and 4 rRNA operons in various combinations. We find that redundancy in tRNA pools is beneficial when nutrients are plentiful and costly under nutrient limitation. This nutrient-dependent cost of redundant tRNA genes stems from upper limits to translation capacity and growth rate, and therefore varies as a function of the maximum growth rate attainable in a given nutrient niche. The loss of redundancy in rRNA genes and tRNA modifying enzymes had similar nutrient-dependent fitness consequences. Importantly, these effects are also contingent upon interactions across translation components, indicating a layered hierarchy from copy number of tRNA and rRNA genes to their expression and downstream processing. Overall, our results indicate both positive and negative selection on redundancy in translation components, depending on a species{\textquoteright} evolutionary history with feasts and famines.

}, keywords = {Biological Evolution, Cost-Benefit Analysis, Escherichia coli, Exercise, Gene Dosage}, issn = {2050-084X}, doi = {10.7554/eLife.81005}, author = {Raval, Parth K and Ngan, Wing Yui and Gallie, Jenna and Agashe, Deepa} } @article {131934, title = {Leafhopper subfamily Hylicinae (Hemiptera: Auchenorrhyncha: Cicadellidae) in the Indian subcontinent with description of new species.}, journal = {Zootaxa}, volume = {5319}, year = {2023}, month = {2023 Jul 27}, pages = {451-500}, abstract = {

The genera and species of Hylicinae reported from the Indian subcontinent are reviewed. Hatigoria zhangi sp. nov. (India: Arunachal Pradesh), Hemisudra indica sp. nov. (India: Manipur), Kalasha confusa sp. nov. (India: Meghalaya), Kalasha manikya sp. nov. (India: Manipur) and Sudra manipurensis sp. nov. (India: Manipur) are described. Genera Hemisudra Schmidt, Hatigoria Distant and Sudra St{\r a}l are new records for India. All the taxa dealt with are illustrated and diagnosed, new taxa are described and illustrated. A revised diagnosis of the subfamily Hylicinae is provided. A revised key to Hylicinae genera of the Indian subcontinent and a checklist are also provided.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.5319.4.1}, author = {Viraktamath, C A and Yeshwanth, H M} } @article {129166, title = {Live-Cell Visualization of Early Stages of Root Colonization by the Vascular Wilt Pathogen Fusarium oxysporum.}, journal = {Methods Mol Biol}, volume = {2659}, year = {2023}, month = {2023}, pages = {73-82}, abstract = {

Fungal phytopathogens induce a variety of pathogenicity symptoms on their hosts. The soilborne vascular wilt pathogen Fusarium oxysporum infects roots of more than 150 different crop species. Initial colonization stages are asymptomatic, likely representing a biotrophic phase of infection, followed by a necrotrophic switch after vascular colonization which results in blockage of the plant xylem and killing of the host. Live-cell microscopy techniques have been successfully employed to study interaction events during fungal colonization of root tissues. This technique is widely used to track fungal development during disease progression. Here, we describe a well-established protocol for generation and screening of fluorescently tagged F. oxysporum transformants, as well as for live-cell imaging of the early colonization stages of F. oxysporum on tomato (Solanum lycopersicum) seedlings. The presented experimental design and techniques involved are also applicable to other root infecting fungi.

}, keywords = {Fusarium, Plant Diseases, Solanum lycopersicum, Virulence}, issn = {1940-6029}, doi = {10.1007/978-1-0716-3159-1_6}, author = {Redkar, Amey and Di Pietro, Antonio and Turr{\`a}, David} } @article {129163, title = {Methyltransferase-independent function of enhancer of zeste homologue 2 maintains tumorigenicity induced by human oncogenic papillomavirus and polyomavirus.}, journal = {Tumour Virus Res}, year = {2023}, month = {2023 May 25}, pages = {200264}, abstract = {

Merkel cell polyomavirus (MCV) and high-risk human papillomavirus (HPV) are human tumor viruses that cause Merkel cell carcinoma (MCC) and oropharyngeal squamous cell carcinoma (OSCC), respectively. HPV E7 and MCV large T (LT) oncoproteins target the retinoblastoma tumor suppressor protein (pRb) through the conserved LxCxE motif. We identified enhancer of zeste homolog 2 (EZH2) as a common host oncoprotein activated by both viral oncoproteins through the pRb binding motif. EZH2 is a catalytic subunit of the polycomb 2 (PRC2) complex that trimethylates histone H3 at lysine 27 (H3K27me3). In MCC tissues EZH2 was highly expressed, irrespective of MCV status. Loss-of-function studies revealed that viral HPV E6/E7 and T antigen expression are required for Ezh2 mRNA expression and that EZH2 is essential for HPV(+)OSCC and MCV(+)MCC cell growth. Furthermore, EZH2 protein degraders reduced cell viability efficiently and rapidly in HPV(+)OSCC and MCV(+)MCC cells, whereas EZH2 histone methyltransferase inhibitors did not affect cell proliferation or viability within the same treatment period. These results suggest that a methyltransferase-independent function of EZH2 contributes to tumorigenesis downstream of two viral oncoproteins, and that direct targeting of EZH2 protein expression could be a promising strategy for the inhibition of tumor growth in HPV(+)OSCC and MCV(+)MCC patients.

}, issn = {2666-6790}, doi = {10.1016/j.tvr.2023.200264}, author = {Khattri, Michelle and Amako, Yutaka and Gibbs, Julia R and Collura, Joseph L and Arora, Reety and Harold, Alexis and Li, Meng Yen and Harms, Paul W and Ezhkova, Elena and Shuda, Masahiro} } @article {125197, title = {Minus-C subfamily has diverged from Classic odorant-binding proteins in honeybees}, journal = {APIDOLOGIE }, volume = {54}, year = {2023}, month = {02/2023}, pages = {12}, abstract = {

Odorant-binding proteins (OBPs) in insects bind to volatile chemical cues that are important in regulating insect behavior. It is hypothesized that OBPs bind with specificity to certain volatiles and may help in transport and delivery to odorant receptors (ORs), and may help in buffering the olfactory response and aid the insect in various behaviors. Honeybees are eusocial insects that perceive olfactory cues and strongly rely on them to perform complex olfactory behaviors. Here, we have identified and annotated odorant-binding proteins and few chemosensory proteins from the genome of the dwarf honey bee, Apis florea, using an exhaustive homology-based bioinformatic pipeline and analyzed the evolutionary relationships between the OBP subfamilies. Our study confirms that the Minus-C subfamily in honey bees has diverged from the Classic subfamily of odorant-binding proteins.

}, doi = {10.1007/s13592-022-00988-5}, author = {Mam, Bhavika and Karpe, Snehal D. and Sowdhamini, Ramanathan} } @article {122346, title = {Molecular and cellular constraints on vesicle traffic evolution.}, journal = {Curr Opin Cell Biol}, volume = {80}, year = {2023}, month = {2023 Jan 05}, pages = {102151}, abstract = {

In eukaryotic cells, the budding and fusion of intracellular transport vesicles is carefully orchestrated in space and time. Locally, a vesicle{\textquoteright}s source compartment, its cargo, and its destination compartment are controlled by dynamic multi-protein specificity modules. Globally, vesicle constituents must be recycled to ensure homeostasis of compartment compositions. The emergence of a novel vesicle pathway therefore requires new specificity modules as well as new recycling routes. Here, we review recent research on local (molecular) constraints on gene module duplication and global (cellular) constraints on intracellular recycling. By studying the evolution of vesicle traffic, we may discover general principles of how complex traits arise via multiple intermediate steps.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2022.102151}, author = {Thattai, Mukund} } @article {130541, title = {Molecular phylogeny, historical biogeography, and classification of Pseudocoladenia butterflies (Lepidoptera: Hesperiidae).}, journal = {Mol Phylogenet Evol}, volume = {186}, year = {2023}, month = {2023 Jun 21}, pages = {107865}, abstract = {

The range of the butterfly genus Pseudocoladenia includes several biodiversity hotspots, such as the Himalayas, mountains of southwestern China, and Sundaland. However, the taxonomic status of some of its species/subspecies remain controversial, and no previous phylogenetic or biogeographic analyses have been conducted. Herein, we determined the systematic relationships and biogeographic history of this genus by reconstructing its phylogeny based on six genes and 69 specimens as representatives of all known species/subspecies. Two species delimitation methods (Bayes Poisson Tree Processes and Bayesian Phylogenetics and Phylogeography) were also employed to assess the status of each taxon. Based on these results and morphological evidence, we identified 12 species and three subspecies in the genus and subsequently classified these into three species groups: P. fatih, P. dea, and P. dan. Five taxa, P. sadakoe (Sonan and Mitono, 1936) stat. nov., P. celebica (Fruhstorfer, 1909) stat. nov., P. fulvescens (Elwes and Edwarda, 1897) stat. nov., P. eacus (Latreille, 1823) stat. nov., and P. fabia (Evans, 1949) stat. nov. were all recognized as independent species. Additionally, two taxa, P. eacus sumatrana (Fruhstorfer, 1909) comb. nov. and P. eacus dhyana (Fruhstorfer, 1909) comb. nov., were placed under P. eacus (Latreille, 1823) stat. nov. as subspecies. Another new species distributed in N. Yunnan, Pseudocoladenia yunnana Fan, Cao \& Hou sp. nov., was discovered and described. Divergence time and ancestral range estimation indicated that the most recent common ancestor of Pseudocoladenia was distributed in the Himalayas-Hengduan Mountain region and Indochina and diverged approximately 14.00\ Ma. Continuous and episodic dispersal, vicariance, and extinction were used to determine the current geographic distribution of the genus. The P. fatih group had a prominently disjunct distribution between the Himalaya-Hengduan Mountain and Taiwan. Meanwhile, the P. dan group was first derived in Indochina and subsequently dispersed into the southeastern Asian archipelagoes. This study provides a reference for the evolutionary route of transoceanic distributed species in Asia and elaborates on the causes of biodiversity.

}, issn = {1095-9513}, doi = {10.1016/j.ympev.2023.107865}, author = {Hou, Yongxiang and Cao, Chenglong and Chiba, Hideyuki and Chang, Zhou and Huang, Siyao and Zhu, Lijuan and Kunte, Krushnamegh and Huang, Zhenfu and Wang, Min and Fan, Xiaoling} } @article {129505, title = {A molecular rotor FLIM probe reveals dynamic coupling between mitochondrial inner membrane fluidity and cellular respiration.}, journal = {Proc Natl Acad Sci U S A}, volume = {120}, year = {2023}, month = {2023 Jun 13}, pages = {e2213241120}, abstract = {

The inner mitochondrial membrane (IMM), housing components of the electron transport chain (ETC), is the site for respiration. The ETC relies on mobile carriers; therefore, it has long been argued that the fluidity of the densely packed IMM can potentially influence ETC flux and cell physiology. However, it is unclear if cells temporally modulate IMM fluidity upon metabolic or other stimulation. Using a photostable, red-shifted, cell-permeable molecular-rotor, Mitorotor-1, we present a multiplexed approach for quantitatively mapping IMM fluidity in living cells. This reveals IMM fluidity to be linked to cellular-respiration and responsive to stimuli. Multiple approaches combining in\ vitro experiments and live-cell fluorescence (FLIM) lifetime imaging microscopy (FLIM) show Mitorotor-1 to robustly report IMM {\textquoteright}microviscosity{\textquoteright}/fluidity through changes in molecular free volume. Interestingly, external osmotic stimuli cause controlled swelling/compaction of mitochondria, thereby revealing a graded Mitorotor-1 response to IMM microviscosity. Lateral diffusion measurements of IMM correlate with microviscosity reported via Mitorotor-1 FLIM-lifetime, showing convergence of independent approaches for measuring IMM local-order. Mitorotor-1 FLIM reveals mitochondrial heterogeneity in IMM fluidity; between-and-within cells and across single mitochondrion. Multiplexed FLIM lifetime imaging of Mitorotor-1 and NADH autofluorescence reveals that IMM fluidity positively correlates with respiration, across individual cells. Remarkably, we find that stimulating respiration, through nutrient deprivation or chemically, also leads to increase in IMM fluidity. These data suggest that modulating IMM fluidity supports enhanced respiratory flux. Our study presents a robust method for measuring IMM fluidity and suggests a dynamic regulatory paradigm of modulating IMM local order on changing metabolic demand.

}, keywords = {Cell Respiration, Membrane Fluidity, Microscopy, Fluorescence, Mitochondrial Membranes, Molecular Probes}, issn = {1091-6490}, doi = {10.1073/pnas.2213241120}, author = {Singh, Gaurav and George, Geen and Raja, Sufi O and Kandaswamy, Ponnuvel and Kumar, Manoj and Thutupalli, Shashi and Laxman, Sunil and Gulyani, Akash} } @article {128092, title = {Multispecies autocatalytic RNA reaction networks in coacervates.}, journal = {Communications Chemistry}, volume = {6}, year = {2023}, month = {2023 May 08}, pages = {91}, abstract = {

Robust localization of self-reproducing autocatalytic chemistries is a key step in the realization of heritable and evolvable chemical systems. While autocatalytic chemical reaction networks already possess attributes such as heritable self-reproduction and evolvability, localizing functional multispecies networks within complex primitive phases, such as coacervates, has remained unexplored. Here, we show the self-reproduction of the Azoarcus ribozyme system within charge-rich coacervates where catalytic ribozymes are produced by the autocatalytic assembly of constituent smaller RNA fragments. We systematically demonstrate the catalytic assembly of active ribozymes within phase-separated coacervates-both in micron-sized droplets as well as in a coalesced macrophase, underscoring the facility of the complex, charge-rich phase to support these reactions in multiple configurations. By constructing multispecies reaction networks, we show that these newly assembled molecules are active, participating both in self- and cross-catalysis within the coacervates. Finally, due to differential molecular transport, these phase-separated compartments endow robustness to the composition of the collectively autocatalytic networks against external perturbations. Altogether, our results establish the formation of multispecies self-reproducing reaction networks in phase-separated compartments which in turn render transient robustness to the network composition.

}, issn = {2399-3669}, doi = {10.1038/s42004-023-00887-5}, author = {Ameta, Sandeep and Kumar, Manoj and Chakraborty, Nayan and Matsubara, Yoshiya J and S, Prashanth and Gandavadi, Dhanush and Thutupalli, Shashi} } @article {120164, title = {Nanobody derived using a peptide epitope from the Spike protein receptor-binding motif inhibits entry of SARS-CoV-2 variants.}, journal = {J Biol Chem}, volume = {299}, year = {2023}, month = {2022 Nov 21}, pages = {102732}, abstract = {

The emergence of new escape mutants of the SARS-CoV-2 virus has escalated its penetration among the human population and has reinstated its status as a global pandemic. Therefore, developing effective antiviral therapy against emerging SARS-CoV variants and other viruses in a short period of time becomes essential. Blocking SARS-CoV-2 entry into human host cells by disrupting the Spike glycoprotein-angiotensin-converting enzyme 2 (ACE2) interaction has already been exploited for vaccine development and monoclonal antibody therapy. Unlike the previous reports, our study used a nine-amino acid peptide from the receptor-binding motif (RBM) of the Spike (S) protein as an epitope. We report the identification of an efficacious nanobody N1.2 that blocks the entry of pseudovirus-containing SARS-CoV-2 Spike as the surface glycoprotein. Moreover, using mCherry fluorescence based reporter assay we observe a more potent neutralizing effect against both the hCoV19 (Wuhan/WIV04/2019) and the Omicron (BA.1) pseudotyped Spike virus with a bivalent version of the N1.2 nanobody. In summary, our study presents a rapid, and efficient methodology to use peptide sequences from a protein-receptor interaction interface as epitopes for screening nanobodies against potential pathogenic targets. We propose that this approach can also be widely extended to target other viruses and pathogens in the future.

}, issn = {1083-351X}, doi = {10.1016/j.jbc.2022.102732}, author = {Mendon, Nivya and Ganie, Rayees and Kesarwani, Shubham and Dileep, Drisya and Sasi, Sarika and Lama, Prakash and Chandra, Anchal and Sirajuddin, Minhajuddin} } @article {137335, title = {Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption.}, journal = {Front Immunol}, volume = {14}, year = {2023}, month = {2023}, pages = {1255478}, abstract = {

The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body{\textquoteright}s own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37{\textquoteright}s mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed an inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as a potential therapeutic avenue to mitigate disease severity. The combination of niacinamide and LL37 is a potent antiviral formulation that targets viral membranes of various variants and can be an effective strategy to overcome vaccine escape.

}, keywords = {Antimicrobial Cationic Peptides, Antiviral Agents, Cathelicidins, COVID-19, Humans, Niacinamide, SARS-CoV-2}, issn = {1664-3224}, doi = {10.3389/fimmu.2023.1255478}, author = {Bhatt, Tanay and Dam, Binita and Khedkar, Sneha Uday and Lall, Sahil and Pandey, Subhashini and Kataria, Sunny and Ajnabi, Johan and Gulzar, Shah-E-Jahan and Dias, Paul M and Waskar, Morris and Raut, Janhavi and Sundaramurthy, Varadharajan and Vemula, Praveen Kumar and Ghatlia, Naresh and Majumdar, Amitabha and Jamora, Colin} } @article {124441, title = {Nitrogen addition and warming modulate the pathogen impact on plant biomass by shifting intraspecific functional traits and reducing species richness}, journal = {JOURNAL OF ECOLOGY }, volume = {111}, year = {2023}, month = {11/2022}, pages = {509-524}, abstract = {

Foliar fungal pathogens can substantially reduce plant biomass. This effect can be modulated by environment conditions, such as soil nitrogen availability and air temperature. The ongoing global changes are altering these variables and thus interact with pathogens to influence plant biomass, but experimental test of their interactions is scarce. We conducted a 4-year field experiment in a Tibetan alpine meadow to examine the interactive effects of nitrogen addition, warming and foliar pathogens (via fungicide application) on plant biomass. We also measured plant functional traits, species richness and abundance to test the possible mechanisms underlying these interactions. Our results showed that foliar fungal pathogens reduced plant community biomass under nitrogen addition, which in turn weakened the positive nitrogen effect on community biomass. Mechanistically, nitrogen addition shifted the plant communities towards fast-growing traits; this happened predominantly because of changes in within-species trait values, including an increase in specific leaf area and height. These trait changes resulted in greater suppression of plant biomass by pathogens, likely because of the trade-offs associated with the allocation of resources to plant growth and defense. Moreover, the reduction in species richness amplified the pathogen effect under nitrogen addition due to the increased density and susceptibility of the most dominant species (i.e. Kobresia capillifolia). Furthermore, warming did not interact with pathogens and nitrogen addition to influence plant community biomass, but their three-way interaction modified the biomass of K. capillifolia. Specifically, warming enhanced the positive effect of nitrogen addition on the biomass of K. capillifolia in the fungicide, low infection plots, while it weakened the nitrogen effect in the no fungicide, high infection plots. Synthesis. Our results demonstrate how pathogens interact with nitrogen addition and warming to influence the biomass of dominant species and the whole plant community. Our study highlights the importance of considering foliar fungal pathogens when assessing ecosystem responses to multiple global change factors.

}, doi = {10.1111/1365-2745.14043}, author = {Yan, Xuebin and Kohli, Mayank and Wen, Yue and Wang, Xiaoyi} } @article {130547, title = {Not teaching evolution is an injustice.}, journal = {Science}, volume = {380}, year = {2023}, month = {2023 Jun 30}, pages = {1303}, abstract = {

Since April, India has been roiled by controversy around the excision of several topics, including evolution and the periodic table, from school textbooks (up to grade 10) by the National Council for Educational Research and Training (NCERT). This was projected as an exercise in "rationalization" of content aimed at reducing the study load on students. The move was opposed by large numbers of academics and worried citizens. As the exclusion of specific topics in history and contemporary politics appeared to be in line with the ideology of the ruling party, many critics assumed that the removal of science topics was also ideologically motivated. In turn, this spurred supporters of NCERT and the government to dismiss all criticism as being entirely political, rather than academic. Both sides in this debate have traded exaggerated accusations of mala fide intent, leading to crucial broader issues being obscured.

}, keywords = {Educational Status, Exercise, Government, Humans, Schools, Students}, issn = {1095-9203}, doi = {10.1126/science.adj3557}, author = {Shashidhara, L S and Joshi, Amitabh} } @article {135859, title = {Novel regulators of mitochondrial genome integrity.}, journal = {J Biosci}, volume = {48}, year = {2023}, month = {2023}, abstract = {

Mitochondrial genomes are unusual in that they have very low mutation rates in coding sequences when compared with animals, yeast, and bacteria. It has been proposed that the mitochondrial (mt) DNA damage is preferentially repaired by homologous recombination (HR). In this short review, we summarize and discuss the well-established and recently identified pathways that help in maintaining the integrity of plant mitochondrial genomes.

}, keywords = {Animals, DNA, Mitochondrial, Genome, Mitochondrial, Genome, Plant, Homologous Recombination, Mitochondria, Plants, Saccharomyces cerevisiae}, issn = {0973-7138}, author = {Nair, Ashwin and Shivaprasad, P V} } @article {135864, title = {Nutritional properties of giant water bug, a traditional edible insect species of North-East India.}, journal = {Bioengineered}, volume = {14}, year = {2023}, month = {2023 Dec}, pages = {2252669}, abstract = {

Edible insects play an important role in human health and food security. Among those, the Giant water bug, (Lep.\& Ser.) is a widely used edible insect known for its aroma, flavor, and therapeutic purposes. In the present study, we investigated the nutritional profile, natural habitat, and feeding behavior of in aquarium conditions. A comparative analysis of male and female insects{\textquoteright} aroma contents and fatty acid (FA) profiles was also conducted. A dry fried male insect yielded volatile oil of 0.96\%/2 g body weight, whereas a dry fried female yielded 0.48\%/5.36 g of body weight. In terms of lipids, fresh male insects had 0.15\%/5.42 g of body weight and fresh female insects had 0.28\%/9.48 g of body weight. There are 24 volatile compounds specific to males, 37 specific to females, and 13 commons to both were identified. 2-Hexen-1-ol, acetate, (Z)- which smells like banana, was prevalently found in males while 4-Octene, 2,6-dimethyl-, [S-(Z)] was prevalently found in female insects. Fatty acids profile analysis detected 32 FA with 12 unique FA from males whereas 22 FA and 3 unique FA were identified from female insects. The SFA percentage present in males and females was 77.44\% and 85.21\%. Males had 6.78\% MUFA content while females have 4.75\%. Males have 18\% PUFA content enriched with DHA, and EPA, while females had 10.04\%. This study revealed that with the presence of a banana-like smell of volatile compound and more MUFA and PUFA in males, the native people of North-East India preferred male over female insects for entomophagy.

}, keywords = {Animals, Body Weight, Edible Insects, Feeding Behavior, Female, India, Male, Nutritive Value}, issn = {2165-5987}, doi = {10.1080/21655979.2023.2252669}, author = {Devi, Mutum R and Ummalyma, Sabeela B and Brockmann, Axel and Raina, Vishakha and Rajashekar, Yallappa} } @article {137336, title = {Opportunities and challenges in Asian bee research and conservation}, journal = {BIOLOGICAL CONSERVATION }, volume = {285}, year = {2023}, month = {09/23}, pages = {110173}, abstract = {

The challenges of bee research in Asia are unique and severe, reflecting different cultures, landscapes, and faunas. Strategies and frameworks developed in North America or Europe may not prove applicable. Virtually none of these species have been assessed by the IUCN and there is a paucity of public data on even the basics of bee distribution. If we do not know the species present, their distribution and threats, we cannot protect them, but our knowledge base is vanishingly small in Asia compared to the rest of the world. To better understand and meet these challenges, this perspective conveys the ideas accumulated over hundreds of years of cumulative study of Asian bees by the authors, including academic, governmental, and other researchers from 13 Asian countries and beyond. We outline the special circumstances of Asian bee research and the current state of affairs, highlight the importance of highly social species as flagships for the lesser-known solitary bees, the dire need for further research for food security, and identify target research areas in need of further study. Finally, we outline a framework via which we will catalyze future research in the region, especially via governmental and other partnerships necessary to effectively conserve species.

}, doi = {10.1016/j.biocon.2023.110173}, author = {Warrit, Natapot and Ascher, John and Basu, Parthib and Belavadi, Vasuki and Brockmann, Axel and et al} } @article {128075, title = {Optimized protocol for assay for transposase-accessible chromatin by sequencing (ATAC-seq) from Drosophila melanogaster brain tissue.}, journal = {STAR Protoc}, volume = {4}, year = {2023}, month = {2023 Apr 18}, pages = {102153}, abstract = {

Transposase-accessible chromatin by sequencing (ATAC-seq) has emerged as an advantageous technique to assess chromatin accessibility owing to the robustness of "tagmentation" process and a relatively faster library preparation. A\ comprehensive ATAC-seq protocol from Drosophila brain tissue is currently unavailable. Here, we have provided a detailed protocol of ATAC-seq assay from Drosophila brain tissue. Starting from dissection and transposition to amplification of libraries has been elaborated. Furthermore, a robust ATAC-seq analysis pipeline has been presented. The protocol can be easily adapted for other soft tissues.

}, issn = {2666-1667}, doi = {10.1016/j.xpro.2023.102153}, author = {Dhall, Jasmine Kaur and Kasturacharya, Nandashree and Pandit, Awadhesh and Cp, Lakshminarayanan} } @article {128076, title = {Overcoming the coupled climate and biodiversity crises and their societal impacts.}, journal = {Science}, volume = {380}, year = {2023}, month = {2023 Apr 21}, pages = {eabl4881}, abstract = {

Earth{\textquoteright}s biodiversity and human societies face pollution, overconsumption of natural resources, urbanization, demographic shifts, social and economic inequalities, and habitat loss, many of which are exacerbated by climate change. Here, we review links among climate, biodiversity, and society and develop a roadmap toward sustainability. These include limiting warming to 1.5{\textdegree}C and effectively conserving and restoring functional ecosystems on 30 to 50\% of land, freshwater, and ocean "scapes." We envision a mosaic of interconnected protected and shared spaces, including intensively used spaces, to strengthen self-sustaining biodiversity, the capacity of people and nature to adapt to and mitigate climate change, and nature{\textquoteright}s contributions to people. Fostering interlinked human, ecosystem, and planetary health for a livable future urgently requires bold implementation of transformative policy interventions through interconnected institutions, governance, and social systems from local to global levels.

}, keywords = {Biodiversity, Climate Change, Conservation of Natural Resources, Ecosystem, Fresh Water, Humans, Urbanization}, issn = {1095-9203}, doi = {10.1126/science.abl4881}, author = {P{\"o}rtner, H-O and Scholes, R J and Arneth, A and Barnes, D K A and Burrows, M T and Diamond, S E and Duarte, C M and Kiessling, W and Leadley, P and Managi, S and McElwee, P and Midgley, G and Ngo, H T and Obura, D and Pascual, U and Sankaran, M and Shin, Y J and Val, A L} } @article {134596, title = {Patterns and consequences of invasion of tropical montane forests by Cestrum aurantiacum Lindl. in the Western Ghats}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION }, year = {2023}, month = {08/2023}, abstract = {

In the montane forest-grassland mosaics of the Western Ghats, land cover conversion to silviculture and agriculture over the last five decades has resulted in both loss of natural habitats and widespread invasion of remnant habitat patches. While invasion of the grassland habitats of the mosaic has been relatively well studied, there have been few attempts to understand the extent to which forest habitats (locally known as sholas) have been affected by the spread of exotic species. Here we examine the patterns and impacts of invasion of shola forest understoreys by Cestrum aurantiacum Lindl., an exotic shrub species. At the landscape scale, we demonstrate that the presence and abundance of this invasive in shola understories is negatively related to distance from tea plantations. Further, the intensity of invasion is higher in areas with greater seasonality of temperature and lower mean annual precipitation. At the patch scale, invasion is greatest at shola edges and away from stream courses. We find that C. aurantiacum abundance has negatively affected the regeneration of native shola tree species as well as the abundance of native shola understorey shrubs. Fifty three percent of invaded plots had no native shrubs present. In plots where both C. aurantiacum and native shrubs were present in large enough numbers, we found evidence of negative spatial dependence between stem locations of C. aurantiacum and native shrubs. Our findings have important implications for the management and conservation of these mosaics.

}, doi = {10.3389/fevo.2023.1198085}, author = {Das, Arundhati A. and Ratnam, Jayashree and Jathanna, Devcharan} } @article {128070, title = {Patterns of understory invasion in invasive timber stands of a tropical sky island.}, journal = {Ecol Evol}, volume = {13}, year = {2023}, month = {2023 Apr}, pages = {e9995}, abstract = {

Current climate and land cover change threaten global mountaintops with increased spread of invasive species. Long-established plantations of invasive trees on these mountaintops can alter their surroundings, further increasing invader-facilitated invasion. Identifying the ecological conditions promoting such associations can help develop better management interventions. The Western Ghats{\textquoteright}s Shola Sky Islands (\>1400 m MSL) host vast stretches of invasive tree plantations that sustain the colonization of other invasive woody, herbaceous, and fern species in their understories. Here, we analyzed vegetation and landscape variables from 232 systematically placed plots in randomly selected grids using non-metric multidimensional scaling and Phi coefficient approaches to examine patterns of association (positive interactions) between understory invasive species with specific invasive overstory species. We also conducted GLMM with zero inflation to determine the influence of environmental variables where such associations occur. We find that understory invasion of multiple species under the canopy of other invasives is widespread across the Shola Sky Islands. Stands of host the colonization of 70\% of non-native invasive species surveyed across the Shola Sky Islands. In particular, the invasion is strongly associated with stands. We also found that climatic variables affect the colonization of understory woody invasive species, while invasion by exotic herbaceous species is associated with the density of road networks. Canopy cover impacts all invasives negatively, while fire incidence was negatively associated with invasion by spp. and the spp. While the restoration of natural habitats primarily targets the highly invasive , less invasive and are often not included. Our study suggests that retaining such invasive species in natural habitats, particularly protected areas, can hinder ongoing grassland restoration efforts by facilitating further invasions by multiple woody and herbaceous species.

}, issn = {2045-7758}, doi = {10.1002/ece3.9995}, author = {Jobin, Varughese and Das, Arundhati and Harikrishnan, C P and Chanda, Ritobroto and Lawrence, Swapna and Robin, V V} } @article {130539, title = {PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase.}, journal = {Life Sci Alliance}, volume = {6}, year = {2023}, month = {2023 Sep}, abstract = {

Phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 5-phosphate (PI5P) are low-abundance phosphoinositides crucial for key cellular events such as endosomal trafficking and autophagy. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) is an enzyme that regulates PI5P in vivo but can act on both PI5P and PI3P in vitro. In this study, we report a role for PIP4K in regulating PI3P levels in Loss-of-function mutants of the only PIP4K gene show reduced cell size in salivary glands. PI3P levels are elevated in and reverting PI3P levels back towards WT, without changes in PI5P levels, can rescue the reduced cell size. mutants also show up-regulation in autophagy and the reduced cell size can be reverted by depleting Atg8a that is required for autophagy. Lastly, increasing PI3P levels in WT can phenocopy the reduction in cell size and associated autophagy up-regulation seen in Thus, our study reports a role for a PIP4K-regulated PI3P pool in the control of autophagy and cell size.

}, keywords = {Animals, Autophagy, Cell Size, Drosophila, Endosomes}, issn = {2575-1077}, doi = {10.26508/lsa.202301920}, author = {Ghosh, Avishek and Venugopal, Aishwarya and Shinde, Dhananjay and Sharma, Sanjeev and Krishnan, Meera and Mathre, Swarna and Krishnan, Harini and Saha, Sankhanil and Raghu, Padinjat} } @article {129504, title = {Plant polymerase IV sensitizes chromatin through histone modifications to preclude spread of silencing into protein-coding domains.}, journal = {Genome Res}, year = {2023}, month = {2023 Jun 05}, abstract = {

Across eukaryotes, gene regulation is manifested via chromatin states roughly distinguished as heterochromatin and euchromatin. The establishment, maintenance, and modulation of the chromatin states is mediated using several factors including chromatin modifiers. However, factors that avoid the intrusion of silencing signals into protein-coding genes are poorly understood. Here we show that a plant specific paralog of RNA polymerase (Pol) II, named Pol IV, is involved in avoidance of facultative heterochromatic marks in protein-coding genes, in addition to its well-established functions in silencing repeats and transposons. In its absence, H3K27 trimethylation (me3) mark intruded the protein-coding genes, more profoundly in genes embedded with repeats. In a subset of genes, spurious transcriptional activity resulted in small(s) RNA production, leading to post-transcriptional gene silencing. We show that such effects are significantly pronounced in rice, a plant with a larger genome with distributed heterochromatin compared with Our results indicate the division of labor among plant-specific polymerases, not just in establishing effective silencing via sRNAs and DNA methylation but also in influencing chromatin boundaries.

}, issn = {1549-5469}, doi = {10.1101/gr.277353.122}, author = {Vivek Hari Sundar G and Swetha, Chenna and Basu, Debjani and Pachamuthu, Kannan and Raju, Steffi and Chakraborty, Tania and Mosher, Rebecca A and Shivaprasad, P V} } @article {134609, title = {Polyfunctional CD4 T-cells correlating with neutralising antibody is a hallmark of COVISHIELDTM and COVAXIN{\textregistered} induced immunity in COVID-19 exposed Indians.}, journal = {NPJ Vaccines}, volume = {8}, year = {2023}, month = {09/2023}, pages = {134}, abstract = {

Detailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN{\textregistered} (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.

}, doi = {10.1038/s41541-023-00731-w}, author = {Rakshit, S. and Babji, S. and Parthiban, C. and Madhavan, R. and Adiga, V. and Sharon, Eveline J and Chetan Kumar, N. and Ahmed, A. and Shivalingaiah, S. and Shashikumar, N. and Johnson, A. R. and Mamatha, V. and Ramesh, N. and Goud, B. R. and Asokan, M. and Mayor, S and Kang, G. and D{\textquoteright}souza, G. and Dias, M. and Vyakarnam, A.} } @article {123071, title = {Potential Self-Peptide Inhibitors of the SARS-CoV-2 Main Protease.}, journal = {J Phys Chem B}, year = {2023}, month = {2023 Jan 23}, abstract = {

The SARS-CoV-2 main protease (M) plays an essential role in viral replication, cleaving viral polyproteins into functional proteins. This makes M an important drug target. M consists of an N-terminal catalytic domain and a C-terminal α-helical domain (MC). Previous studies have shown that peptides derived from a given protein sequence (self-peptides) can affect the folding and, in turn, the function of that protein. Since the SARS-CoV-1 MC is known to stabilize its M and regulate its function, we hypothesized that SARS-CoV-2 MC-derived self-peptides may modulate the folding and the function of SARS-CoV-2 M. To test this, we studied the folding of MC in the presence of various self-peptides using coarse-grained structure-based models and molecular dynamics simulations. In these simulations of MC and one self-peptide, we found that two self-peptides, the α1-helix and the loop between α4 and α5 (loop4), could replace the equivalent native sequences in the MC structure. Replacement of either sequence in full-length M should, in principle, be able to perturb M function albeit through different mechanisms. Some general principles for the rational design of self-peptide inhibitors emerge: The simulations show that prefolded self-peptides are more likely to replace native sequences than those which do not possess structure. Additionally, the α1-helix self-peptide is kinetically stable and once inserted rarely exchanges with the native α1-helix, while the loop4 self-peptide is easily replaced by the native loop4, making it less useful for modulating function. In summary, a prefolded α1-derived peptide should be able to inhibit SARS-CoV-2 M function.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.2c05917}, author = {Banerjee, Arkadeep and Gosavi, Shachi} } @article {125196, title = {Prioritizing India{\textquoteright}s landscapes for biodiversity, ecosystem services and human well-being}, journal = {NATURE SUSTAINABILITY }, year = {2023}, month = {02/2023}, abstract = {

Biodiversity conservation and human well-being are tightly interlinked. Yet, mismatches in the scale at which these two priority issues are planned and implemented have exacerbated biodiversity loss, erosion of ecosystem services and declining human quality of life. India houses the second largest human population on the planet, while \< 5\% of the country{\textquoteright}s land area is effectively protected for conservation. This warrants landscape-level conservation planning through a judicious mix of land-sharing and land-sparing approaches combined with the co-production of ecosystem services. Through a multifaceted assessment, we prioritize spatial extents of land parcels that, in the face of anthropogenic threats, can safeguard conservation landscapes across India{\textquoteright}s biogeographic zones. We found that only a fraction (similar to 15\%) of the priority areas identified here are encompassed under India{\textquoteright}s extant Protected Area network, and furthermore, that several landscapes of high importance were omitted from all previous global-scale assessments. We then examined the spatial congruence of priority areas with administrative units earmarked for economic development by the Indian government and propose management zoning through state-driven and participatory approaches. Our spatially explicit insights can help meet the twin goals of biodiversity conservation and sustainable development in India and other countries across the Global South.

Biodiversity conservation is critical for promoting ecosystem services and human well-being, but current conservation efforts fail to protect most high priority zones. A mix of land-sparing and land-sharing is needed to safeguard critical ecosystems in India and across the Global South.

}, doi = {10.1038/s41893-023-01063-2}, author = {Srivathsa, Arjun and Vasudev, Divya and Nair, Tanaya and Chakrabarti, Stotra and Chanchani, Pranav and DeFries, Ruth and Deomurari, Arpit and Dutta, Sutirtha and Ghose, Dipankar and Goswami, Varun R. and Nayak, Rajat and Neelakantan, Amrita and Thatte, Prachi and Vaidyanathan, Srinivas and Verma, Madhu and Krishnaswamy, Jagdish and Sankaran, Mahesh and Ramakrishnan, Uma} } @article {128078, title = {Prognostic association of immunoproteasome expression in solid tumours is governed by the immediate immune environment.}, journal = {Mol Oncol}, year = {2023}, month = {2023 Apr 25}, abstract = {

Induction of immunoproteasome (IP) expression in tumour cells can enhance antigen presentation and immunogenicity. Recently, the overexpression of IP genes has been associated with better prognosis and response to immune checkpoint blockade (ICB) therapies in melanoma. However, the extent of this association in other solid tumours and how that is influenced by tumour cell-intrinsic and cell-extrinsic factors remain unclear. Here, we address this by exploring the gene expression patterns from available bulk and single-cell transcriptomic data of primary tumours. We find that tumours with high-IP expression exhibit cytotoxic immune cell infiltration and upregulation of IFN-γ and TNF-α pathways in tumour cells. However, the association of IP expression with overall survival (TCGA cohort) and response to ICB therapy (non-TCGA cohorts) is tumour-type specific (better in non-small-cell lung, breast, bladder and thymus; and worse in glioma and renal) and is greatly influenced by pro- or antitumourigenic immune cell infiltration patterns. This emphasises the need for considering immune cell infiltration patterns, along with IP expression, as a prognostic biomarker to predict overall survival or response to ICB therapies in solid tumours, besides melanoma.

}, issn = {1878-0261}, doi = {10.1002/1878-0261.13443}, author = {Kumar, Rahul and Dhaka, Bhavya and Sahoo, Sarthak and Jolly, Mohit Kumar and Sabarinathan, Radhakrishnan} } @article {131935, title = {Prolongation of mitosis is associated with enhanced endogenous DNA damage in fission yeast.}, journal = {MicroPubl Biol}, volume = {2023}, year = {2023}, month = {2023}, abstract = {

Mitosis is usually shorter than other phases of the cell cycle and maintains a consistent duration despite variations in cell size and spindle size. This suggests the existence of a compensatory mechanism that ensures a short duration, possibly as a protective measure against irreversible damage, such as DNA damage. To explore the link between prolonged mitosis and DNA damage, we develop a microscopy-based assay utilizing Rad52-GFP as a marker for mitotic DNA damage. Through this assay, we provide evidence that mutants with prolonged mitosis exhibit increased Rad52 puncta, indicating an elevation in endogenous DNA damage.

}, issn = {2578-9430}, doi = {10.17912/micropub.biology.000911}, author = {Jain, Ishutesh and Tran, Phong T} } @article {128089, title = {Quantitative fluorescence emission anisotropy microscopy for implementing homo-fluorescence resonance energy transfer measurements in living cells}, journal = {Mol Biol Cell.}, volume = {34}, year = {2023}, month = {05/2023}, abstract = {

Quantitative fluorescence emission anisotropy microscopy reveals the organization of fluorescently labeled cellular components and allows their characterization in terms of changes in either rotational diffusion or homo-F{\"o}rster{\textquoteright}s energy transfer characteristics in living cells. These properties provide insights into molecular organization, such as orientation, confinement, and oligomerization in situ. Here we elucidate how quantitative measurements of anisotropy using multiple microscope systems may be made by bringing out the main parameters that influence the quantification of fluorescence emission anisotropy. We focus on a variety of parameters that contribute to errors associated with the measurement of emission anisotropy in a microscope. These include the requirement for adequate photon counts for the necessary discrimination of anisotropy values, the influence of extinction ratios of the illumination source, the detector system, the role of numerical aperture, and excitation wavelength. All these parameters also affect the ability to capture the dynamic range of emission anisotropy necessary for quantifying its reduction due to homo-FRET and other processes. Finally, we provide easily implementable tests to assess whether homo-FRET is a cause for the observed emission depolarization.

}, doi = {10.1091/mbc.E22-09-0446.}, author = {van Zanten, Thomas and Greeshma, Pradeep S and Mayor, S} } @article {131300, title = {Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2.}, journal = {Elife}, volume = {12}, year = {2023}, month = {07/2023}, abstract = {

Loss of endoplasmic reticular (ER) Ca2+ activates store-operated Ca2+ entry (SOCE) by causing the ER localized Ca2+ sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IP3R), an ER-localized IP3-gated Ca2+ channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca2+ is attenuated by loss of IP3Rs, and restored by expression of IP3Rs even when they cannot release Ca2+, but only if the IP3Rs can bind IP3. Imaging studies demonstrate that IP3Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP3-binding site, but not a pore. Convergent regulation by IP3Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP3.

}, doi = {10.7554/eLife.80447}, author = {Chakraborty, P. and Deb, B. K. and Arige, V. and Musthafa, T. and Malik, S. and Yule, D. I. and Taylor, C.W. and Hasan, Gaiti} } @article {123128, title = {Regulatory mechanisms of c-di-AMP synthase (MsDisA) protein from Mycobacterium smegmatis revealed by a structure - function analysis.}, journal = {Protein Sci}, year = {2023}, month = {2023 Jan 20}, pages = {e4568}, abstract = {

Cyclic-di-nucleotide based secondary messengers regulate various physiological functions, including stress responses in bacteria. Cyclic diadenosine monophosphate (c-di-AMP) has recently emerged as a crucial second messenger with implications in processes including osmoregulation, antibiotic resistance, biofilm formation, virulence, DNA repair, ion homeostasis and sporulation, and has potential therapeutic applications. The contrasting activities of the enzymes diadenylate cyclase (DAC) and phosphodiesterase (PDE) determine the equilibrium levels of c-di-AMP. Although, c-di-AMP is suspected of playing an essential role in the pathophysiology of bacterial infections and in regulating host-pathogen interactions, the mechanisms of its regulation remain relatively unexplored in mycobacteria. In this report, we biochemically and structurally characterize the c-di-AMP synthase (MsDisA) from Mycobacterium smegmatis. The enzyme activity is regulated by pH and substrate concentration; conditions of significance in the homoeostasis of c-di-AMP levels. Substrate binding stimulates conformational changes in the protein, and pApA and ppApA are synthetic intermediates detectable when enzyme efficiency is low. Unlike the orthologous B. subtilis enzyme, MsDisA does not bind to, and its activity is not influenced in the presence of DNA. Further, we have determined the cryo-EM structure of MsDisA, revealing asymmetry in its structure in contrast to the symmetric crystal structure of T. maritima DisA. We also demonstrate that the N-terminal minimal region alone is sufficient and essential for oligomerization and catalytic activity. Our data shed light on the regulation of mycobacterial DisA and possible future directions to pursue. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.4568}, author = {Gautam, Sudhanshu and Mahapa, Avisek and Yeramala, Lahari and Gandhi, Apoorv and Krishnan, Sushma and Vinothkumar, Kutti R and Chatterji, Dipankar} } @article {129153, title = {Reliable and robust control of nucleus centering is contingent on nonequilibrium force patterns.}, journal = {iScience}, volume = {26}, year = {2023}, month = {2023 May 19}, pages = {106665}, abstract = {

Cell centers their division apparatus to ensure symmetric cell division, a challenging task when the governing dynamics is stochastic. Using fission yeast, we show that the patterning of nonequilibrium polymerization forces of microtubule (MT) bundles the precise localization of spindle pole body (SPB), and hence the division septum, at the onset of mitosis. We define two cellular objectives, , the mean SPB position relative to the geometric center, and , the variance of the SPB position, which are sensitive to genetic perturbations that change cell length, MT bundle number/orientation, and MT dynamics. We show that simultaneous control of reliability and robustness is required to minimize septum positioning error achieved by the wild type (WT). A stochastic model for the MT-based nucleus centering, with parameters measured directly or estimated using Bayesian inference, recapitulates the maximum fidelity of WT. Using this, we perform a sensitivity analysis of the parameters that control nuclear centering.

}, issn = {2589-0042}, doi = {10.1016/j.isci.2023.106665}, author = {Jain, Ishutesh and Rao, Madan and Tran, Phong T} } @article {133180, title = {Replacement of the native cis prolines by alanine leads to simplification of the complex folding mechanism of a small globular protein.}, journal = {Biophys J}, year = {2023}, month = {2023 Aug 18}, abstract = {

The folding mechanism of MNEI, a single-chain variant of naturally occurring double-chain monellin, is complex, with multiple parallel refolding channels. To determine whether its folding energy landscape could be simplified, the two native cis-prolines, Pro41 and Pro93, were mutated, singly and together, to Ala. The stability of P93A was the same as that of the wild-type protein, pWT; however, P41A and P41AP93A were destabilized by \~{}0.9\ kcal mol. The effects of the mutations on the very fast, fast, slow, and very slow phases of folding were studied. They showed that heterogeneity in the unfolded state arises due to cis to trans isomerization of the Gly92-Pro93 peptide bond. The Pro41 to Ala mutation abolished the very slow phase of folding, whereas surprisingly, the Pro93 to Ala mutation abolished the very fast phase of folding. Double-jump, interrupted folding experiments indicated that two sequential trans to cis proline isomerization steps, of the Gly92-Pro93 peptide bond followed by the Arg40-Pro41 peptide bond, lead to the formation of the native state. They also revealed the accumulation of a late native-like intermediate, N, which differs from the native state in the isomeric status of the Arg40-Pro41 bond, as well as in a few tertiary contacts as monitored by near-UV CD measurements. The Pro to Ala mutations not only eliminated the cis to trans Pro isomerization reaction in the unfolded state, but also the two trans to cis Pro isomerization reactions during folding. By doing so, and by differentially affecting the relative stabilities of folding intermediates, the mutations resulted in a simplification of the folding mechanism. The two Pro to Ala mutations together accelerate folding to such an extent that the native state forms more than 1000-fold faster than in the case of pWT.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2023.08.012}, author = {Kaushik, Anushka and Udgaonkar, Jayant B} } @article {121924, title = {Revisiting the Burden Borne by Fumarase: Enzymatic Hydration of an Olefin.}, journal = {Biochemistry}, year = {2023}, month = {2023 Jan 03}, abstract = {

Fumarate hydratase (FH) is a remarkable catalyst that decreases the free energy of the catalyzed reaction by 30 kcal mol, much larger than most exceptional enzymes with extraordinary catalytic rates. Two classes of FH are observed in nature: class-I and class-II, which have different folds, yet catalyze the same reversible hydration/dehydration reaction of the dicarboxylic acids fumarate/malate, with equal efficiencies. Using class-I FH from the hyperthermophilic archaeon (Mj) as a model along with comparative analysis with the only other available class-I FH structure from (Lm), we provide insights into the molecular mechanism of catalysis in this class of enzymes. The structure of MjFH apo-protein has been determined, revealing that large intersubunit rearrangements occur across apo- and holo-protein forms, with a largely preorganized active site for substrate binding. Site-directed mutagenesis of active site residues, kinetic analysis, and computational studies, including density functional theory (DFT) and natural population analysis, together show that residues interacting with the carboxylate group of the substrate play a pivotal role in catalysis. Our study establishes that an electrostatic network at the active site of class-I FH polarizes the substrate fumarate through interactions with its carboxylate groups, thereby permitting an easier addition of a water molecule across the olefinic bond. We propose a mechanism of catalysis in FH that occurs through transition-state stabilization involving the distortion of the electronic structure of the substrate olefinic bond mediated by the charge polarization of the bound substrate at the enzyme active site.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.2c00541}, author = {Bellur, Asutosh and Das, Soumik and Jayaraman, Vijay and Behera, Sudarshan and Suryavanshi, Arpitha and Balasubramanian, Sundaram and Balaram, Padmanabhan and Jindal, Garima and Balaram, Hemalatha} } @article {134597, title = {Revisiting the Role of Genetic Variation in Adaptation}, journal = {AMERICAN NATURALIST }, year = {2023}, month = {09/2023}, abstract = {

Evolutionary biologists have thought about the role of genetic variation during adaptation for a very long time-before we understood the organization of the genetic code, the provenance of ge-netic variation, and how such variation influenced the phenotypes on which natural selection acts. Half a century after the discovery of the structure of DNA and the unraveling of the genetic code, we have a rich understanding of these problems and the means to both delve deeper and widen our perspective across organisms and natural pop-ulations. The 2022 Vice Presidential Symposium of the American So-ciety of Naturalists highlighted examples of recent insights into the role of genetic variation in adaptive processes, which are compiled in this special section. The work was conducted in different parts of the world, included theoretical and empirical studies with diverse or-ganisms, and addressed distinct aspects of how genetic variation influ-ences adaptation. In our introductory article to the special section, we discuss some important recent insights about the generation and maintenance of genetic variation, its impacts on phenotype and fit-ness, its fate in natural populations, and its role in driving adaptation. By placing the special section articles in the broader context of recent developments, we hope that this overview will also serve as a useful in-troduction to the field.

}, doi = {10.1086/726012}, author = {Agashe, Deepa and Sane, Mrudula and Singhal, Shivansh} } @article {131290, title = {Roof of the world: Home and border in the genomic era}, journal = {Molecular Ecology Resources}, year = {2023}, month = {06/2023}, abstract = {

Himalaya and the Tibetan Plateau, known as the {\textquoteleft}land of snow{\textquoteright} and the {\textquoteleft}roof of the world{\textquoteright}, is home to tens of millions of indigenous people who live with a staggering amount of biological diversity. In the past decade scientists have applied genomic tools and methods to substantially advance the understanding of phylogeography and genetic mechanisms behind high-elevation adaptation of local biota. However, contributions from indigenous researchers and native institutions are underrepresented in this scientific endeavour. We point to the higher degree of indigenous contribution within the discipline of conservation biology and how recognizing the prominence of traditional ecological knowledge (TEK) could deliver keen molecular ecological insights. Since the Himalaya-Tibet ecological interface spans five countries, comprehensive biogeographical and phylogeographical taxon sampling in the region requires multi-national collaborations across indigenous lands as well as indigenous community participation at both national and international levels. For the next generation of indigenous molecular ecologists, researching and cataloguing the evolutionary history and genetic information of the Tibetan and Himalayan landscape is a race against the melting glacier. At the roof of the world, their scientific judgement and stewardship will have environmental impacts that percolate far beyond indigenous lands.

}, doi = {10.1111/1755-0998.13827}, author = {Da, W. and Rana, S. K. and Bawa, K. and Kunte, K. and Wang, Z.} } @article {126623, title = {Safe space in the woods: Mechanistic spatial models for predicting risks of human-bear conflicts in India}, journal = {BIOTROPICA }, volume = {55}, year = {2023}, month = {03/2023}, pages = {504-516}, abstract = {

Human-wildlife interactions can have negative consequences when they involve large carnivores. Spatial risk modelling could serve as a useful management approach for predicting and pre-emptively mitigating negative interactions. We present a mechanistic modelling framework and examine interactions between humans and sloth bears (Melursus ursinus) in a multi-use forest landscape of central India. We first assessed patterns and determinants of bear distribution across the landscape using indirect sign surveys. At the same spatial scale, we then estimated spatial probabilities of bear attacks on people using information from 675 interviews with local residents, incorporating estimates of distribution probabilities from the previous step. We found the average occupancy probability across 128 grid-cells to be 0.77 (SE = 0.03). Bear occupancy was influenced by terrain ruggedness, forest composition and configuration, vegetation productivity and size of human settlements. The average probability of a bear attack in any given grid-cell was 0.61 (SE = 0.03), mostly determined by bear occurrence patterns, forest cover, terrain ruggedness, and size of human settlements. Using spatial information on people{\textquoteright}s dependence on forest resources, we identified locations with the highest risk of bear attacks. Our study demonstrates that human attacks by bears-generally believed to be random or incidental-in fact showed deterministic patterns. Our framework can be applied to other scenarios involving human-wildlife conflicts. Based on our findings, we propose that a proactive co-management approach which involves collaboration between wildlife managers and local residents could help better manage human-bear conflicts in central India and elsewhere across the species{\textquoteright} range.

}, doi = {10.1111/btp.13204}, author = {Puri, Mahi and Srivathsa, Arjun and Karanth, Krithi K. and Patel, Imran and Kumar, N. Samba} } @article {123072, title = {SARS-CoV-2 infection dynamics and genomic surveillance to detect variants in wastewater - a longitudinal study in Bengaluru, India.}, journal = {Lancet Reg Health Southeast Asia}, year = {2023}, month = {2023 Jan 18}, pages = {100151}, abstract = {

BACKGROUND: Environmental surveillance (ES) of a pathogen is crucial for understanding the community load of disease. As an early warning system, ES for SARS-CoV-2 has complemented routine diagnostic surveillance by capturing near real-time virus circulation at a population level.

METHODS: In this longitudinal study conducted between January 2022 and June 2022 in 28 sewershed sites in Bengaluru city (\~{}11 million inhabitants), we quantified weekly SARS-CoV-2 RNA concentrations to track infection dynamics and provide evidence of change in the relative abundance of emerging variants.

FINDINGS: We describe an early warning system using the exponentially weighted moving average control chart and demonstrate how SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 8-14 days earlier in wastewater than in clinical data. This was further corroborated by showing that the estimated number of infections is strongly correlated with SARS-CoV-2 RNA copies detected in the wastewater. Using a deconvolution matrix, we detected emerging variants of concern up to two months earlier in wastewater samples. In addition, we found a huge diversity in variants detected in wastewater compared to clinical samples. The findings from this study have been discussed regularly with local authorities to inform policy-making decisions.

INTERPRETATION: Our study highlights that quantifying viral titre, correlating it with a known number of cases in the area, and combined with genomic surveillance helps in tracking variants of concern (VOC) over time and space, enabling timely and making informed policy decisions.

FUNDING: This work has been supported by funding from the Rockefeller Foundation grant to National Centre for Biological Sciences (TIFR) and the Indian Council of Medical Research grant to (FI) Tata Institute for Genetics and Society and Tata Trusts.

}, issn = {2772-3682}, doi = {10.1016/j.lansea.2023.100151}, author = {Lamba, Sanjay and Ganesan, Sutharsan and Daroch, Namrta and Paul, Kiran and Joshi, Soumya Gopal and Sreenivas, Darshan and Nataraj, Annamalai and Srikantaiah, Vishwanath and Mishra, Rakesh and Ramakrishnan, Uma and Ishtiaq, Farah} } @article {129162, title = {Shifts in mutation spectra enhance access to beneficial mutations.}, journal = {Proc Natl Acad Sci U S A.}, volume = {120}, year = {2023}, month = {05/2023}, pages = {e2207355120}, abstract = {

Biased mutation spectra are pervasive, with wide variation in the magnitude of mutational biases that influence genome evolution and adaptation. How do such diverse biases evolve? Our experiments show that changing the mutation spectrum allows populations to sample previously undersampled mutational space, including beneficial mutations. The resulting shift in the distribution of fitness effects is advantageous: Beneficial mutation supply and beneficial pleiotropy both increase, while deleterious load reduces. More broadly, simulations indicate that reducing or reversing the direction of a long-term bias is always selectively favored. Such changes in mutation bias can occur easily via altered function of DNA repair genes. A phylogenetic analysis shows that these genes are repeatedly gained and lost in bacterial lineages, leading to frequent bias shifts in opposite directions. Thus, shifts in mutation spectra may evolve under selection and can directly alter the outcome of adaptive evolution by facilitating access to beneficial mutations.

}, doi = {10.1073/pnas.2207355120}, author = {Sane, Mrudula and Diwan, Gaurav D and Bhat, BA and Wahl, LM and Agashe, Deepa} } @article {128091, title = {SOS-independent bacterial DNA damage responses:~diverse mechanisms, unifying function.}, journal = {Curr Opin Microbiol}, volume = {73}, year = {2023}, month = {2023 May 04}, pages = {102323}, abstract = {

Cells across domains of life have dedicated pathways to sense and respond to DNA damage. These responses are broadly termed as DNA damage responses (DDRs). In bacteria, the best\ studied DDR is the Save our Soul (SOS) response. More recently, several SOS-independent DDRs have also been discovered. Studies further report diversity in the\ types of repair proteins present across bacterial species as well as differences in their mechanisms of action. Although the primary function of DDRs is preservation of genome integrity, the diverse organization, conservation, and function of bacterial DDRs raises important questions about how genome error correction mechanisms could influence or be influenced by the genomes that encode them. In this review, we discuss recent insights on three SOS-independent bacterial DDRs. We consider open questions in our understanding of how diversity in response and repair mechanisms is generated, and how action of these pathways is regulated in cells to ensure maintenance of genome integrity.

}, issn = {1879-0364}, doi = {10.1016/j.mib.2023.102323}, author = {Kamat, Aditya and Badrinarayanan, Anjana} } @article {130543, title = {A STIM dependent dopamine-neuropeptide axis maintains the larval drive to feed and grow in Drosophila.}, journal = {PLoS Genet}, volume = {19}, year = {2023}, month = {2023 Jun 26}, pages = {e1010435}, abstract = {

Appropriate nutritional intake is essential for organismal survival. In holometabolous insects such as Drosophila melanogaster, the quality and quantity of food ingested as larvae determines adult size and fecundity. Here we have identified a subset of dopaminergic neurons (THD{\textquoteright}) that maintain the larval motivation to feed. Dopamine release from these neurons requires the ER Ca2+ sensor STIM. Larvae with loss of STIM stop feeding and growing, whereas expression of STIM in THD{\textquoteright} neurons rescues feeding, growth and viability of STIM null mutants to a significant extent. Moreover STIM is essential for maintaining excitability and release of dopamine from THD{\textquoteright} neurons. Optogenetic stimulation of THD{\textquoteright} neurons activated neuropeptidergic cells, including median neuro secretory cells that secrete insulin-like peptides. Loss of STIM in THD{\textquoteright} cells alters the developmental profile of specific insulin-like peptides including ilp3. Loss of ilp3 partially rescues STIM null mutants and inappropriate expression of ilp3 in larvae affects development and growth. In summary we have identified a novel STIM-dependent function of dopamine neurons that modulates developmental changes in larval feeding behaviour and growth.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1010435}, author = {Kasturacharya, Nandashree and Dhall, Jasmine Kaur and Hasan, Gaiti} } @article {122345, title = {Structural heterogeneity of the Rieske iron-sulfur protein in a yeast complex III.}, journal = {IUCrJ}, volume = {10}, year = {2023}, month = {2023 Jan 01}, pages = {1-3}, abstract = {

Cryo-EM has been used to analyze the positions of the hydrophilic domain of the Rieske iron{\textendash}sulfur protein in a yeast complex III under various redox and substrate/inhibitor conditions.

}, keywords = {Electron Transport Complex III, Iron-Sulfur Proteins, Mitochondrial Membranes, Saccharomyces cerevisiae}, issn = {2052-2525}, doi = {10.1107/S2052252522012003}, author = {Vinothkumar, Kutti R} } @article {126669, title = {Structural modelling and dynamics of full-length of TLR10 sheds light on possible modes of dimerization, ligand binding and mechanism of action.}, journal = {Curr Res Struct Biol}, volume = {5}, year = {2023}, month = {2023}, pages = {100097}, abstract = {

Toll like receptors (TLRs) play a pivotal role in innate and adaptive immunity. There are 10 TLRs in the human genome, of which TLR10 is the least characterized. Genetic polymorphism of TLR10 has been shown to be associated with multiple diseases including tuberculosis and rheumatoid arthritis. TLR10 consists of an extracellular domain (ECD), a single-pass transmembrane (TM) helix and intracellular TIR (Toll/Interleukin-1 receptor) domain. ECD is employed for ligand recognition and the intracellular domain interacts with other TIR domain-containing adapter proteins for signal transduction. Experimental structure of ECD or TM domain is not available for TLR10. In this study, we have modelled multiple forms of TLR10-ECD dimers, such as closed and open forms, starting from available structures of homologues. Subsequently, multiple full-length TLR10 homodimer models were generated by utilizing homology modelling and protein-protein docking. The dynamics of these models in membrane-aqueous environment revealed the global motion of ECD and TIR domain towards membrane bilayer. The TIR domain residues exhibited high root mean square fluctuation compared to ECD. The {\textquoteright}closed form{\textquoteright} model was observed to be energetically more favorable than {\textquoteright}open form{\textquoteright} model. The evaluation of persistent interchain interactions, along with their conservation score, unveiled critical residues for each model. Further, the binding of dsRNA to TLR10 was modelled by defined and blind docking approaches. Differential binding of dsRNA to the protomers of TLR10 was observed upon simulation that could provide clues on ligand disassociation. Dynamic network analysis revealed that the {\textquoteright}open form{\textquoteright} model can be the functional form while {\textquoteright}closed form{\textquoteright} model can be the apo form of TLR10.

}, issn = {2665-928X}, doi = {10.1016/j.crstbi.2023.100097}, author = {Tiwari, Vikas and Sowdhamini, R} } @article {124445, title = {Structural organization of RDGB (retinal degeneration B), a multi-domain lipid transfer protein: a molecular modelling and simulation based approach.}, journal = {J Biomol Struct Dyn}, year = {2023}, month = {2023 Feb 20}, pages = {1-15}, abstract = {

Lipid transfer proteins (LTPs) that shuttle lipids at membrane contact sites (MCS) play an important role in maintaining cellular homeostasis. One such important LTP is the Retinal Degeneration B (RDGB) protein. RDGB is localized at the MCS formed between the endoplasmic reticulum (ER) and the apical plasma membrane (PM) in photoreceptors where it transfers phosphatidylinositol (PI) during G-protein coupled phospholipase C signalling. Previously, the C-terminal domains of RDGB have been shown to be essential for its function and accurate localization. In this study, using integrative modelling we predict the structure of entire RDGB protein in complex with the ER membrane protein VAP. The structure of RDGB has then been used to decipher the structural features of the protein important for its orientation at the contact site. Using this structure, we identify two lysine residues in the C-terminal helix of the LNS2 domain important for interaction with the PM. Using molecular docking, we also identify an unstructured region USR1, immediately c-terminal to the PITP domain that is important for the interaction of RDGB with VAP. Overall the 10.06 nm length of the predicted RDGB-VAP complex spans the distance between the PM and ER and is consistent with the cytoplasmic gap between the ER and PM measured by transmission electron microscopy in photoreceptors. Overall our model explains the topology of the RDGB-VAP complex at this ER-PM contact site and paves the way for analysis of lipid transfer function in this setting.Communicated by Ramaswamy H. Sarma.

}, issn = {1538-0254}, doi = {10.1080/07391102.2023.2179545}, author = {Krishnan, Harini and Basak, Bishal and Nath, Vaisaly R and Mishra, Shirish and Raghu, Padinjat} } @article {128079, title = {Structural rationale to understand the effect of disease-associated mutations on Myotubularin.}, journal = {Curr Res Struct Biol}, volume = {5}, year = {2023}, month = {2023}, pages = {100100}, abstract = {

Myotubularin or MTM1 is a lipid phosphatase that regulates vesicular trafficking in the cell. The gene is mutated in a severe form of muscular disease, X-linked myotubular myopathy or XLMTM, affecting 1 in 50,000 newborn males worldwide. There have been several studies on the disease pathology of XLMTM, but the structural effects of missense mutations of MTM1 are underexplored due to the unavailability of a crystal structure. MTM1 consists of three domains-a lipid-binding N-terminal GRAM domain, the phosphatase domain and a coiled-coil domain which aids dimerisation of Myotubularin homologs. While most mutations reported to date map to the phosphatase domain of MTM1, the other two domains on the sequence are also frequently mutated in XLMTM. To understand the overall structural and functional effects of missense mutations on MTM1, we curated several missense mutations and performed and studies. Apart from significantly impaired binding to substrate, abrogation of phosphatase activity was observed for a few mutants. Possible long-range effects of mutations from non-catalytic domains on phosphatase activity were observed as well. Coiled-coil domain mutants have been characterised here for the first time in XLMTM literature.

}, issn = {2665-928X}, doi = {10.1016/j.crstbi.2023.100100}, author = {Bhattacharyya, Teerna and Ghosh, Avishek and Verma, Shailya and Raghu, Padinjat and Sowdhamini, Ramanathan} } @article {135860, title = {Structural snapshots of Mycobacterium tuberculosis enolase reveal dual mode of 2PG binding and its implication in enzyme catalysis.}, journal = {IUCrJ}, volume = {10}, year = {2023}, month = {2023 Nov 01}, pages = {738-753}, abstract = {

Enolase, a ubiquitous enzyme, catalyzes the reversible conversion of 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP) in the glycolytic pathway of organisms of all three domains of life. The underlying mechanism of the 2PG to PEP conversion has been studied in great detail in previous work, however that of the reverse reaction remains to be explored. Here we present structural snapshots of Mycobacterium tuberculosis (Mtb) enolase in apo, PEP-bound and two 2PG-bound forms as it catalyzes the conversion of PEP to 2PG. The two 2PG-bound complex structures differed in the conformation of the bound product (2PG) viz the widely reported canonical conformation and a novel binding pose, which we refer to here as the alternate conformation. Notably, we observed two major differences compared with the forward reaction: the presence of Mg is non-obligatory for the reaction and 2PG assumes an alternate conformation that is likely to facilitate its dissociation from the active site. Molecular dynamics studies and binding free energy calculations further substantiate that the alternate conformation of 2PG causes distortions in both metal ion coordination and hydrogen-bonding interactions, resulting in an increased flexibility of the active-site loops and aiding product release. Taken together, this study presents a probable mechanism involved in PEP to 2PG catalysis that is likely to be mediated by the conformational change of 2PG at the active site.

}, keywords = {Catalysis, Models, Molecular, Mycobacterium tuberculosis, Phosphopyruvate Hydratase, Protein Conformation}, issn = {2052-2525}, doi = {10.1107/S2052252523008485}, author = {Ahmad, Mohammed and Jha, Bhavya and Bose, Sucharita and Tiwari, Satish and Dwivedy, Abhisek and Kar, Deepshikha and Pal, Ravikant and Mariadasse, Richard and Parish, Tanya and Jeyakanthan, Jeyaraman and Vinothkumar, Kutti R and Biswal, Bichitra Kumar} } @article {126684, title = {Structure modelling of odorant receptor from and identification of potential repellent molecules.}, journal = {Comput Struct Biotechnol J}, volume = {21}, year = {2023}, month = {2023}, pages = {2204-2214}, abstract = {

Odorant receptors (ORs) are important class of proteins involved in olfactory behaviour of insects. These are GPCR-like heptahelical transmembrane proteins with inverted topology compared to GPCR and require a co-receptor (ORco) for their function. OR function can be modulated through small molecules and negative modulation can be beneficial in case of disease vectors like . OR4 of is implicated in host recognition through human odour. is a vector for viruses that spread diseases like dengue, Zika and Chikungunya. In this study, we have attempted to model the full-length structure of OR4 and the ORco of due to lack of experimental structure. Further, we have screened a library of natural compounds (\>0.3 million) along with known repellent molecules against ORco and OR4. Many natural compounds, including those from plants like (Holy Basil) and (Black pepper) were found to have better binding affinity towards ORco compared to known repellents like DEET providing an alternative to existing repellent molecules. For specific inhibitor of OR4, several natural compounds (including those from plant like Mulberry) were identified. Further, we have utilized multiple docking approaches and conservation analysis to understand the interaction between OR4 and ORco. It was observed that the residues from the seventh transmembrane helix of OR4 and pore forming helix of ORco could play an important role along with known intracellular loop 3 residues in mediating the heteromer formation of OR and ORco.

}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.03.005}, author = {Tiwari, Vikas and Sowdhamini, R} } @article {135857, title = {A Survey of Models of Cell Membranes: Toward a New Understanding of Membrane Organization.}, journal = {Cold Spring Harb Perspect Biol}, volume = {15}, year = {2023}, month = {2023 Oct 03}, abstract = {

The cell membrane, the boundary that separates living cells from their environment, has been the subject of study for over a century. The fluid-mosaic model of Singer and Nicolson in 1972 proposed the plasma membrane as a two-dimensional fluid composed of lipids and proteins. Fifty years hence, advances in biophysical and biochemical tools, particularly optical imaging techniques, have allowed for a better understanding of the physical nature, organization, and composition of cell membranes. This has been made possible by visualizing membrane heterogeneities and their dynamics and appreciating the asymmetrical arrangement of lipids in living cell membranes. Despite these advances, mechanisms underlying the local spatiotemporal organization of membrane components remain unclear. This review surveys various models of membrane organization, culminating in a new model that incorporates nonequilibrium processes and forces exerted by interactions with extramembrane elements such as the actin cytoskeleton. The proposed model provides a comprehensive understanding of membrane organization, taking into account the dynamic nature of the cell membrane and its interactions with its immediate environment.

}, keywords = {Actin Cytoskeleton, Cell Membrane, Membrane Lipids, Proteins}, issn = {1943-0264}, doi = {10.1101/cshperspect.a041394}, author = {Mayor, Satyajit and Bhat, Abrar and Kusumi, Akihiro} } @article {125199, title = {Synthetic Data Resource and Benchmarks for Time Cell Analysis and Detection Algorithms.}, journal = {eNeuro}, year = {2023}, month = {2023 Feb 21}, abstract = {

Hippocampal CA1 cells take part in reliable, time-locked activity sequences in tasks that involve an association between temporally separated stimuli, in a manner that tiles the interval between the stimuli. Such cells have been termed time cells. Here we adopt a first-principles approach to comparing diverse analysis and detection algorithms for identifying time cells. We generated synthetic activity datasets using calcium signals recorded from the mouse hippocampus using 2-Photon imaging, as template response waveforms. We assigned known, ground truth values to perturbations applied to perfect activity signals, including noise, calcium event width, timing imprecision, hit-trial ratio and background (untuned) activity. We tested a range of published and new algorithms and their variants on this dataset. We find that most algorithms correctly classify over 80\% of cells, but have different balances between true and false positives, and different sensitivity to the five categories of perturbation. Reassuringly, most methods are reasonably robust to perturbations, including background activity, and show good concordance in classification of time cells. The same algorithms were also used to analyse and identify time cells in experimental physiology datasets recorded and most show good concordance.Numerous approaches have been developed to analyze time cells and neuronal activity sequences, but it is not clear if their classifications match, nor how sensitive they are to various sources of data variability. We provide two main contributions to address this: 1) A resource to generate ground truth labelled synthetic 2-P Calcium activity data with defined distributions for confounds such as noise and background activity, and 2) a survey of several methods for analyzing time-cell data using our synthetic data as ground truth.As a further resource, we provide a library of efficient C++ implementations of several algorithms with a Python interface. The synthetic dataset and its generation code are useful for profiling future methods, testing analysis toolchains, and as input to computational and experimental models of sequence detection.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0007-22.2023}, author = {Ananthamurthy, Kambadur G and Bhalla, Upinder S} } @article {131294, title = {Tanshinone IIA targeting cell signaling pathways: a plausible paradigm for cancer therapy.}, journal = {Pharmacol Rep}, year = {2023}, month = {2023 Jul 13}, abstract = {

Natural compounds originating from plants offer a wide range of pharmacological potential and have traditionally been used to treat a wide range of diseases including cancer. Tanshinone IIA (Tan IIA), a bioactive molecule found in the roots of the Traditional Chinese Medicine (TCM) herb Salvia miltiorrhiza, has been shown to have remarkable anticancer properties through several mechanisms, such as inhibition of tumor cell growth and proliferation, metastasis, invasion, and angiogenesis, as well as induction of apoptosis and autophagy. It has demonstrated excellent anticancer efficacy against cell lines from breast, cervical, colorectal, gastric, lung, and prostate cancer by modulating multiple signaling pathways including PI3K/Akt, JAK/STAT, IGF-1R, and Bcl-2-Caspase pathways. This review focuses on the role of Tan IIA in the treatment of various cancers, as well as the underlying molecular mechanisms.

}, issn = {2299-5684}, doi = {10.1007/s43440-023-00507-y}, author = {Alam, Syed Sahajada Mahafujul and Samanta, Arijit and Uddin, Faizan and Ali, Safdar and Hoque, Mehboob} } @article {121923, title = {The tempo and mode of character evolution in the assembly of mimetic communities.}, journal = {Proc Natl Acad Sci U S A}, volume = {120}, year = {2023}, month = {2023 Jan 03}, pages = {e2203724120}, abstract = {

Multitrait adaptive evolution is shaped by factors such as phylogenetic and functional constraints as well as the intensity and direction of selection. The tempo and mode of such multitrait evolution can differentially impact the assembly of biological communities. Batesian mimicry, in which undefended prey gain a fitness advantage by evolving a resemblance to aposematic models, involves adaptive evolution of multiple traits such as color patterns and flight morphology. To elucidate the evolutionary mechanisms of such multitrait adaptations, we evaluated the tempo and mode of adaptive convergence in flight morphology and color patterns in mimetic butterfly communities. We found that compared with Batesian mimics or nonmimetic sister species, models showed significantly faster rates of aposematic trait evolution, creating adaptive peaks for mimicry. At the community level, the degree of mimetic resemblance between mimics and models was positively correlated with the rate of character evolution, but independent of phylogenetic relatedness. Monomorphic mimics and female-limited mimics converged on the color patterns of models to a similar degree, showing that there were no constraints on mimetic trait evolution with respect to sex-specific selections. Convergence was driven by the greater lability of color patterns, which evolved at significantly faster rates than the phylogenetically conserved flight morphological traits, indicating that the two traits evolve under differential selection pressures and/or functional and genetic constraints. These community-wide patterns show that during the assembly of a community, the tempo of adaptive evolution is nonlinear, and specific to the underlying functional relationships and key traits that define the community.

}, keywords = {Animals, Biological Evolution, Biological Mimicry, Biota, Butterflies, Excipients, Female, Male, Phylogeny, Predatory Behavior}, issn = {1091-6490}, doi = {10.1073/pnas.2203724120}, author = {Basu, Dipendra Nath and Bhaumik, Vaishali and Kunte, Krushnamegh} } @article {133183, title = {Temporal effects of sugar intake on fly local search and honey bee dance behaviour.}, journal = {J Comp Physiol A Neuroethol Sens Neural Behav Physiol}, year = {2023}, month = {2023 Aug 25}, abstract = {

Honey bees communicate flight navigational information of profitable food to nestmates via their dance, a small-scale walking pattern, inside the nest. Hungry flies and honey bee foragers exhibit a sugar-elicited search involving path integration that bears a resemblance to dance behaviour. This study aimed to investigate the temporal dynamics of the initiation of sugar-elicited search and dance behaviour, using a comparative approach. Passive displacement experiments showed that feeding and the initiation of search could be spatially and temporally dissociated. Sugar intake increased the probability of initiating a search but the actual onset of walking triggers the path integration system to guide the search. When prevented from walking after feeding, flies and bees maintained their motivation for a path integration-based search for a duration of 3\ min. In flies, turning and associated characters were significantly reduced during this period but remained higher than in flies without sugar stimulus. These results suggest that sugar elicits two independent behavioural responses: path integration and increased turning, with the initiation and duration of path integration system being temporally restricted. Honey bee dance experiments demonstrated that the motivation of foragers to initiate dance persisted for 15\ min, while the number of circuits declined after 3\ min following sugar ingestion. Based on these findings, we propose that food intake during foraging increases the probability to initiate locomotor behaviours involving the path integration system in both flies and honey bees, and this ancestral connection might have been co-opted and elaborated during the evolution of dance communication by honey bees.

}, issn = {1432-1351}, doi = {10.1007/s00359-023-01670-6}, author = {Shakeel, Manal and Brockmann, Axel} } @article {130536, title = {Temporal variability of a soundscape near a mid-oceanic atoll in the northern Indian ocean}, journal = {PROGRESS IN OCEANOGRAPHY }, volume = {214}, year = {2023}, month = {06/2023}, pages = {103033}, abstract = {

Soundscape ecology in the context of physical oceanographic features is an emerging area of research revealing interactions between physically, biologically and anthropogenically driven sounds and their sources. Sound-scapes can shape and reveal distributions of a range of species, from fish larvae to whales, within marine eco-systems. The northern Indian Ocean is a region of high environmental variability driven by seasonally reversing monsoonal winds. The mid-oceanic islands within these waters consist of steep slopes forming a crucial interface between shallow reef and deep oceanic habitats. Studies on soundscape are limited in these waters. The aim of this study was to characterize major sound sources off the southern and northern side of the Kavaratti atoll in Lakshadweep islands, India, located at the northern part of the Laccadive-Maldives-Chagos Ridge. A first look at shallow water soundscapes are provided here using passive acoustic monitoring, and how they correlate with satellite-derived oceanographic variables. Geophonic and biophonic sources across different frequency bands are identified with three major choruses - a dusk fish chorus, a midnight chorus that is speculated to be produced by myctophids, and a snapping shrimp night chorus. Low frequency biophonic choruses peaked in inter-monsoon months (January to March), while low frequency geophonic sound levels peaked during monsoon months (June to October) and increased with wind speed. The dusk fish chorus and the midnight chorus (at the south site) decreased with increasing sea surface salinity, while the snapping shrimp chorus (at the south site) increased with increasing sea surface salinity. Snapping shrimp chorus levels increased with decreasing wind speed. The dusk fish chorus peaked during full and waning moon, and the midnight and snapping shrimp choruses peaked during new moon periods. The sources and patterns described in this study will help compare with future soundscape and sound pressure level measurements within this region. This will be useful in the context of a changing climate and for planning future developmental projects on the islands. Reef choruses link with peak larval recruitment, spawning, or feeding activities, and further investigation into the peak calling times reported here will help uncover the function of choruses. Expanding the collection of passive acoustic monitoring data and oceanographic measurements over longer timescales will significantly advance {\textquoteright}soundscape oceanography{\textquoteright}.

}, doi = {DOI10.1016/j.pocean.2023.103033}, author = {Panicker, Divya and Stafford, Kathleen M.} } @article {137346, title = {A theoretical perspective on Waddington{\textquoteright}s genetic assimilation experiments.}, journal = {Proc Natl Acad Sci U S A}, volume = {120}, year = {2023}, month = {2023 Dec 19}, pages = {e2309760120}, abstract = {

Genetic assimilation is the process by which a phenotype that is initially induced by an environmental stimulus becomes stably inherited in the absence of the stimulus after a few generations of selection. While the concept has attracted much debate after being introduced by C. H. Waddington 70 y ago, there have been few experiments to quantitatively characterize the phenomenon. Here, we revisit and organize the results of Waddington{\textquoteright}s original experiments and follow-up studies that attempted to replicate his results. We then present a theoretical model to illustrate the process of genetic assimilation and highlight several aspects that we think require further quantitative studies, including the gradual increase of penetrance, the statistics of delay in assimilation, and the frequency of unviability during selection. Our model captures Waddington{\textquoteright}s picture of developmental paths in a canalized landscape using a stochastic dynamical system with alternative trajectories that can be controlled by either external signals or internal variables. It also reconciles two descriptions of the phenomenon-Waddington{\textquoteright}s, expressed in terms of an individual organism{\textquoteright}s developmental paths, and that of Bateman in terms of the population distribution crossing a hypothetical threshold. Our results provide theoretical insight into the concepts of canalization, phenotypic plasticity, and genetic assimilation.

}, keywords = {Adaptation, Physiological, Biological Evolution, Epigenesis, Genetic, Models, Genetic, Penetrance, Phenotype}, issn = {1091-6490}, doi = {10.1073/pnas.2309760120}, author = {Raju, Archishman and Xue, BingKan and Leibler, Stanislas} } @article {137344, title = {Through the looking glass: attempting to predict future opportunities and challenges in experimental biology.}, journal = {J Exp Biol}, volume = {226}, year = {2023}, month = {2023 Dec 15}, abstract = {

To celebrate its centenary year, Journal of Experimental Biology (JEB) commissioned a collection of articles examining the past, present and future of experimental biology. This Commentary closes the collection by considering the important research opportunities and challenges that await us in the future. We expect that researchers will harness the power of technological advances, such as {\textquoteright}-omics{\textquoteright} and gene editing, to probe resistance and resilience to environmental change as well as other organismal responses. The capacity to handle large data sets will allow high-resolution data to be collected for individual animals and to understand population, species and community responses. The availability of large data sets will also place greater emphasis on approaches such as modeling and simulations. Finally, the increasing sophistication of biologgers will allow more comprehensive data to be collected for individual animals in the wild. Collectively, these approaches will provide an unprecedented understanding of {\textquoteright}how animals work{\textquoteright} as well as keys to safeguarding animals at a time when anthropogenic activities are degrading the natural environment.

}, keywords = {Animals, Environment, Genomics}, issn = {1477-9145}, doi = {10.1242/jeb.246921}, author = {Gilmour, Kathleen M and Daley, Monica A and Egginton, Stuart and Kelber, Almut and McHenry, Matthew J and Patek, Sheila N and Sane, Sanjay P and Schulte, Patricia M and Terblanche, John S and Wright, Patricia A and Franklin, Craig E} } @article {133185, title = {Tolerance to aerial exposure influences distributional patterns in multi-species intertidal seagrass meadows.}, journal = {Mar Environ Res}, volume = {191}, year = {2023}, month = {2023 Aug 19}, pages = {106146}, abstract = {

Multi-specific seagrass meadow assemblages dominate most tropical intertidal regions but the relative role of environmental stress in determining distribution patterns is still uncertain. Here we combine observational and experimental approaches to examine aerial exposure as a factor driving species occurrence patterns in intertidal meadows of the Andaman archipelago, where up to 6 seagrass species co-occur. In the studied meadow, patterns of exposure did not map onto distance from the coast, instead creating a patchy matrix of exposure, based on fine-scale bathymetric differences. Distributional surveys showed that seagrass species were similarly patchy, often tracking the degree of aerial exposure during low tide. While some species (Halophila ovalis, Halophila minor, and Thalassia hemprichii) frequently occurred in submerged or subtidal areas and were rarely found in completely exposed areas, other species (Cymodocea rotundata, Halophila beccarii, and Halodule uninervis) also occupied areas that were subject to partial or complete aerial exposure during low tide. To confirm this pattern, we used field-based transplant experiments, employing a natural gradient of tidal exposure to subject six seagrass species to different desiccation exposure times. After a month, H. beccarii and H. uninervis transplants survived in areas that sustained more than 3\ h of aerial tidal exposure without significant mortality, compared with other species (H. ovalis, H. minor, T. hemprichii, C. rotundata) that showed dramatic shoot mortality at the same exposure regimes. For all species, 4\ h represented the upper limit of exposure, in both experimental and distributional studies. However, despite their wider tolerance of exposure to air, H. beccarii and H. uninervis did not dominate the entire meadow. This could be a result either of their poor tolerance to other environmental factors or their lower competitive abilities among other mechanisms. This suggests that in tropical multi-specific meadows, strong environmental filters could override clear intertidal zonation to create patchy matrices based on species tolerances.

}, issn = {1879-0291}, doi = {10.1016/j.marenvres.2023.106146}, author = {Rao, Rachana and Alcoverro, Teresa and Kongari, Phoolmani and Yoayela, Saw and Arthur, Rohan and D{\textquoteright}Souza, Elrika} } @article {131295, title = {Topcats and underdogs: intraguild interactions among three apex carnivores across Asia{\textquoteright}s forestscapes.}, journal = {Biol Rev Camb Philos Soc}, year = {2023}, month = {2023 Jul 14}, abstract = {

Intraguild interactions among carnivores have long held the fascination of ecologists. Ranging from competition to facilitation and coexistence, these interactions and their complex interplay influence everything from species persistence to ecosystem functioning. Yet, the patterns and pathways of such interactions are far from understood in tropical forest systems, particularly across countries in the Global South. Here, we examined the determinants and consequences of competitive interactions between dholes Cuon alpinus and the two large felids (leopards Panthera pardus and tigers Panthera tigris) with which they most commonly co-occur across Asia. Using a combination of traditional and novel data sources (N = 118), we integrate information from spatial, temporal, and dietary niche dimensions. These three species have faced catastrophic declines in their extent of co-occurrence over the past century; most of their source populations are now confined to Protected Areas. Analysis of dyadic interactions between species pairs showed a clear social hierarchy. Tigers were dominant over dholes, although pack strength in dholes helped ameliorate some of these effects; leopards were subordinate to dholes. Population-level spatio-temporal interactions assessed at 25 locations across Asia did not show a clear pattern of overlap or avoidance between species pairs. Diet-profile assessments indicated that wild ungulate biomass consumption by tigers was highest, while leopards consumed more primate and livestock prey as compared to their co-predators. In terms of prey offtake (ratio of wild prey biomass consumed to biomass available), the three species together harvested 0.4-30.2\% of available prey, with the highest offtake recorded from the location where the carnivores reach very high densities. When re-examined in the context of prey availability and offtake, locations with low wild prey availability showed spatial avoidance and temporal overlap among the carnivore pairs, and locations with high wild prey availability showed spatial overlap and temporal segregation. Based on these observations, we make predictions for 40 Protected Areas in India where temporally synchronous estimates of predator and prey densities are available. We expect that low prey availability will lead to higher competition, and in extreme cases, to the complete exclusion of one or more species. In Protected Areas with high prey availability, we expect intraguild coexistence and conspecific competition among carnivores, with spill-over to forest-edge habitats and subsequent prey-switching to livestock. We stress that dhole-leopard-tiger co-occurrence across their range is facilitated through an intricate yet fragile balance between prey availability, and intraguild and conspecific competition. Data gaps and limitations notwithstanding, our study shows how insights from fundamental ecology can be of immense utility for applied aspects like large predator conservation and management of human-carnivore interactions. Our findings also highlight potential avenues for future research on tropical carnivores that can broaden current understanding of intraguild competition in forest systems of Asia and beyond.

}, issn = {1469-185X}, doi = {10.1111/brv.12998}, author = {Srivathsa, Arjun and Ramachandran, Vivek and Saravanan, Pooja and Sureshbabu, Abhijith and Ganguly, Divyajyoti and Ramakrishnan, Uma} } @article {123068, title = {Towards evolutionary predictions: Current promises and challenges.}, journal = {Evol Appl}, volume = {16}, year = {2023}, month = {2023 Jan}, pages = {3-21}, abstract = {

Evolution has traditionally been a historical and descriptive science, and predicting future evolutionary processes has long been considered impossible. However, evolutionary predictions are increasingly being developed and used in medicine, agriculture, biotechnology and conservation biology. Evolutionary predictions may be used for different purposes, such as to prepare for the future, to try and change the course of evolution or to determine how well we understand evolutionary processes. Similarly, the exact aspect of the evolved population that we want to predict may also differ. For example, we could try to predict which genotype will dominate, the fitness of the population or the extinction probability of a population. In addition, there are many uses of evolutionary predictions that may not always be recognized as such. The main goal of this review is to increase awareness of methods and data in different research fields by showing the breadth of situations in which evolutionary predictions are made. We describe how diverse evolutionary predictions share a common structure described by the predictive scope, time scale and precision. Then, by using examples ranging from SARS-CoV2 and influenza to CRISPR-based gene drives and sustainable product formation in biotechnology, we discuss the methods for predicting evolution, the factors that affect predictability and how predictions can be used to prevent evolution in undesirable directions or to promote beneficial evolution (i.e. evolutionary control). We hope that this review will stimulate collaboration between fields by establishing a common language for evolutionary predictions.

}, issn = {1752-4571}, doi = {10.1111/eva.13513}, author = {Wortel, Meike T and Agashe, Deepa and Bailey, Susan F and Bank, Claudia and Bisschop, Karen and Blankers, Thomas and Cairns, Johannes and Colizzi, Enrico Sandro and Cusseddu, Davide and Desai, Michael M and van Dijk, Bram and Egas, Martijn and Ellers, Jacintha and Groot, Astrid T and Heckel, David G and Johnson, Marcelle L and Kraaijeveld, Ken and Krug, Joachim and Laan, Liedewij and L{\"a}ssig, Michael and Lind, Peter A and Meijer, Jeroen and Noble, Luke M and Okasha, Samir and Rainey, Paul B and Rozen, Daniel E and Shitut, Shraddha and Tans, Sander J and Tenaillon, Olivier and Teot{\'o}nio, Henrique and de Visser, J Arjan G M and Visser, Marcel E and Vroomans, Renske M A and Werner, Gijsbert D A and Wertheim, Bregje and Pennings, Pleuni S} } @article {137339, title = {Tracking Sugar-Elicited Local Searching Behavior in Drosophila.}, journal = {J Vis Exp}, year = {2023}, month = {2023 Nov 17}, abstract = {

Foraging behavior is essential for the survival of organisms as it enables them to locate and acquire essential food resources. In Drosophila, hunger triggers a distinct search behavior following the consumption of small quantities of a sugar solution. This report presents a simple experimental setup to study sugar-elicited search behavior with the aim of uncovering the underlying mechanisms. Minute quantities of concentrated sugar solution elicit sustained searching behavior in flies. The involvement of path integration in this behavior has been established, as flies utilize their trajectory to return to the sugar location. The most recent findings provide evidence of temporal modulation in the initiation and intensity of the search behavior after sugar intake. We have also used this setup for artificial activation of specific taste-receptor neurons in the pharynx, which elicits the search behavior. The Drosophila neurogenetic toolkit offers a diverse array of tools and techniques that can be combined with the sugar-elicited search behavior paradigm to study the neural and genetic mechanisms underlying foraging. Understanding the neural basis of hunger-driven searching behavior in flies contributes to the field of neurobiology as a whole, offering insights into the regulatory mechanisms that govern feeding behaviors not only in other organisms but also in humans.

}, keywords = {Animals, Appetitive Behavior, Carbohydrates, Drosophila, Drosophila melanogaster, Drosophila Proteins, Feeding Behavior, Humans, Sugars}, issn = {1940-087X}, doi = {10.3791/65955}, author = {Shakeel, Manal and Kaushik, Shivam and Tanimura, Teiichi and Brockmann, Axel and Kain, Pinky} } @article {128080, title = {Transcription factor condensates and signaling driven transcription.}, journal = {Nucleus}, volume = {14}, year = {2023}, month = {2023 Dec}, pages = {2205758}, abstract = {

Transcription Factor (TF) condensates are a heterogenous mix of RNA, DNA, and multiple co-factor proteins capable of modulating the transcriptional response of the cell. The dynamic nature and the spatial location of TF-condensates in the 3D nuclear space is believed to provide a fast response, which is on the same pace as the signaling cascade and yet ever-so-specific in the crowded environment of the nucleus. However, the current understanding of how TF-condensates can achieve these feet so quickly and efficiently is still unclear. In this review, we draw parallels with other protein condensates and share our speculations on how the nucleus uses these TF-condensates to achieve high transcriptional specificity and fidelity. We discuss the various constituents of TF-condensates, their properties, and the known and unknown functions of TF-condensates with a particular focus on steroid signaling-induced transcriptional programs.

}, keywords = {Cell Nucleus, Chromatin, DNA, Signal Transduction, Transcription Factors}, issn = {1949-1042}, doi = {10.1080/19491034.2023.2205758}, author = {Mann, Rajat and Notani, Dimple} } @article {129503, title = {Transcriptome data analysis of primary cardiomyopathies reveals perturbations in arachidonic acid metabolism.}, journal = {Front Cardiovasc Med}, volume = {10}, year = {2023}, month = {2023}, pages = {1110119}, abstract = {

INTRODUCTION: Cardiomyopathies are complex heart diseases with significant prevalence around the world. Among these, primary forms are the major contributors to heart failure and sudden cardiac death. As a high-energy demanding engine, the heart utilizes fatty acids, glucose, amino acid, lactate and ketone bodies for energy to meet its requirement. However, continuous myocardial stress and cardiomyopathies drive towards metabolic impairment that advances heart failure (HF) pathogenesis. So far, metabolic profile correlation across different cardiomyopathies remains poorly understood.

METHODS: In this study, we systematically explore metabolic differences amongst primary cardiomyopathies. By assessing the metabolic gene expression of all primary cardiomyopathies, we highlight the significantly shared and distinct metabolic pathways that may represent specialized adaptations to unique cellular demands. We utilized publicly available RNA-seq datasets to profile global changes in the above diseases (|| >= 0.28 and BH\  0.1) and performed gene set analysis (GSA) using the PAGE statistics on KEGG pathways.

RESULTS: Our analysis demonstrates that genes in arachidonic acid metabolism (AA) are significantly perturbed across cardiomyopathies. In particular, the arachidonic acid metabolism gene interacts with fibroblast marker genes and can potentially influence fibrosis during cardiomyopathy.

CONCLUSION: The profound significance of AA metabolism within the cardiovascular system renders it a key player in modulating the phenotypes of cardiomyopathies.

}, issn = {2297-055X}, doi = {10.3389/fcvm.2023.1110119}, author = {Chauhan, Pankaj Kumar and Sowdhamini, Ramanathan} } @article {126632, title = {Tropical agricultural wooded land uses support high site use of forest birds}, journal = {Biological Conservation}, volume = {281}, year = {2023}, month = {05/2023}, pages = {109986}, abstract = {

Agricultural expansion has been responsible for the large-scale modification of forest ecosystems globally. In many regions, this has resulted in the creation of heterogenous landscapes comprised of cleared agricultural lands, and semi-natural and natural wooded land uses such as agroforests and secondary forests. These wooded land uses can play an important role in supporting forest biodiversity. In a tropical agricultural landscape of Northeast India, we investigate how wooded land uses affect site use by forest specialist, forest generalist and open-country bird species, in comparison to a protected area. We also investigate the effects of site vegetation characteristics, surrounding forest cover and distance to the protected area. Using multi-species occupancy models, we found that wooded land uses support high site use of the three forest specialization groups. We attribute the high site use of forest species in wooded land uses to the similarity in site vegetation characteristics between these land uses and the protected area. In addition, high forest cover at, and neighbouring, our sampling sites, and habitat connectivity also contributed towards supporting high site use of forest species. However, for some species across the three groups, a few site vegetation characteristics and surrounding forest cover had a subtle influence. Our study showcases the supplementary role of low-intensity agricultural landscapes as habitat for forest birds, provided that wooded land uses outside protected areas are well maintained. In so doing, it contributes valuable insights into land management practices that support biodiversity in heterogeneous agri-cultural landscapes.

}, doi = {10.1016/j.biocon.2023.109986}, author = {Syiem, BL and Driscoll, Don A. and Vasudev, Divya and Goswami, Varun R.} } @article {135852, title = {Trunks and treetops: integrating terrestrial and arboreal camera-trap surveys to document elusive mammal communities in India}, journal = {MAMMAL RESEARCH}, year = {2023}, month = {09/2023}, abstract = {

Tropical rainforest canopies harbor nearly half of the world{\textquoteright}s biodiversity. Previous research on rainforest ecosystems has primarily focused on the terrestrial stratum, leading to a limited understanding of forest canopies. Camera traps have seen a wide application in the studies of terrestrial mammals, but their utility for documenting arboreal mammal communities has been far more limited. Financial resources, field training, and access to equipment and logistical constraints may have precluded researchers from undertaking systematic arboreal camera surveys, especially in the Global South countries. We deployed arboreal and terrestrial cameras to document the mammal assemblage in Kadumane estate, Western Ghats, India. During April-May 2022, we documented 3 exclusively arboreal, 11 semi-arboreal and 14 terrestrial species, using 16 cameras in the canopies and 13 cameras on the ground. Using rarefaction curves, we find that 648 trap-nights were sufficient to document all the arboreal species, while \> 1350 trap-nights of additional effort would have been required to document all the terrestrial species in our study site. For each species, we generated an arboreality index (calculated from proportional capture rates) to gauge its propensity for arboreal habits. We also compared the efficacy of using different baits; species responses to shrimp-dry fish baits indicated a reduction in rodent captures when carnivore captures were higher. Our study deliberates on the resources, logistical considerations, and advantages of arboreal camera surveys to study mammal assemblages in forest canopies. Importantly, we highlight the utility of such surveys for understanding the ecology of rare, elusive, and hitherto under-studied species that may be threatened with extinction.

}, doi = {10.1007/s13364-023-00714-1}, author = {Nazareth, Orvill and Srivathsa, Arjun and Ramachandran, Vivek} } @article {130535, title = {Two-component molecular motor driven by a GTPase cycle}, journal = {NATURE PHYSICS}, year = {2023}, month = {05/2023}, abstract = {

ATPases can cyclically convert free energy into mechanical work. Now, it is shown that the GTPase Rab5 can also perform mechanical work as part of a two-component molecular motor with the tethering protein EEA1.

ATPases are a group of enzymes that can cyclically convert the free energy of ATP hydrolysis into mechanical work. GTPases are another class of enzymes that are predominantly associated with signal transduction processes, but their role in mechanotransduction is less established. It was previously shown that the binding of the GTPase Rab5 to the tethering protein EEA1 induces a large conformational change in EEA1 from a rigid, extended to a flexible, collapsed state. This entropic collapse of EEA1 gives rise to an effective force that can pull tethered membranes closer. It currently remains unclear if EEA1 can return from the collapsed to the extended conformation without the aid of chaperone proteins. Here we show that EEA1 in a bulk solution can undergo multiple flexibility transition cycles driven by the energetics of Rab5 binding and unbinding as well as GTP hydrolysis. Each cycle can perform up to 20k(B)T of mechanical work. Hence, Rab5 and EEA1 constitute a two-component molecular motor driven by the chemical energy derived from the Rab5 GTPase cycle. We conclude that tethering proteins and their small GTPase partners can have active mechanical roles in membrane trafficking.

}, doi = {10.1038/s41567-023-02009-3}, author = {Singh, Anupam and Soler, Joan Antoni and Lauer, Janelle and Grill, Stephan W. and Jahnel, Marcus and Zerial, Marino and Thutupalli, Shashi} } @article {136527, title = {Understanding molecular signaling cascades in neural disease using multi-resolution models.}, journal = {Curr Opin Neurobiol}, volume = {83}, year = {2023}, month = {2023 Nov 14}, pages = {102808}, abstract = {

If the genome defines the program for the operations of a cell, signaling networks execute it. These cascades of chemical, cell-biological, structural, and trafficking events span milliseconds (e.g., synaptic release) to potentially a lifetime (e.g., stabilization of dendritic spines). In principle almost every aspect of neuronal function, particularly at the synapse, depends on signaling. Thus dysfunction of these cascades, whether through mutations, local dysregulation, or infection, leads to disease. The sheer complexity of these pathways is matched by the range of diseases and the diversity of their phenotypes. In this review, we discuss how to build computational models, how these models are essential to tackle this complexity, and the benefits of using families of models at different levels of detail to understand signaling in health and disease.

}, issn = {1873-6882}, doi = {10.1016/j.conb.2023.102808}, author = {Viswan, Nisha Ann and Bhalla, Upinder Singh} } @article {128069, title = {Unusual Relationship between Iron Deprivation and Organophosphate Hydrolase Expression.}, journal = {Appl Environ Microbiol}, year = {2023}, month = {2023 Apr 19}, pages = {e0190322}, abstract = {

Organophosphate hydrolases (OPH), hitherto known to hydrolyze the third ester bond of organophosphate (OP) insecticides and nerve agents, have recently been shown to interact with outer membrane transport components, namely, TonB and ExbB/ExbD. In an OPH negative background, Sphingopyxis wildii cells failed to transport ferric enterobactin and showed retarded growth under iron-limiting conditions. We now show the OPH-encoding organophosphate degradation () gene from Sphingobium fuliginis ATCC 27551 to be part of the iron regulon. A -box motif found to be overlapping with the transcription start site (TSS) of the gene coordinates with an iron responsive element (IRE) RNA motif identified in the 5{\textquoteright} coding region of the mRNA to tightly regulate gene expression. The -box motif serves as a target for the Fur repressor in the presence of iron. A decrease in iron concentration leads to the derepression of . IRE RNA inhibits the translation of mRNA and serves as a target for apo-aconitase (IRP). The IRP recruited by the IRE RNA abrogates IRE-mediated translational inhibition. Our findings establish a novel, multilayered, iron-responsive regulation that is crucial for OPH function in the transport of siderophore-mediated iron uptake. Sphingobium fuliginis, a soil-dwelling microbe isolated from agricultural soils, was shown to degrade a variety of insecticides and pesticides. These synthetic chemicals function as potent neurotoxins, and they belong to a class of chemicals termed organophosphates. codes for OPH, an enzyme that has been shown to be involved in the metabolism of several organophosphates and their derivatives. Interestingly, OPH has also been shown to facilitate siderophore-mediated iron uptake in and in another Sphingomonad, namely, , implying that this organophosphate-metabolizing protein has a role in iron homeostasis, as well. Our research dissects the underlying molecular mechanisms linking iron to the expression of OPH, prompting a reconsideration of the role of OPH in Sphingomonads and a reevaluation of the evolutionary origins of the OPH proteins from soil bacteria.

}, issn = {1098-5336}, doi = {10.1128/aem.01903-22}, author = {Nandavaram, Aparna and Nandakumar, Anirudh and Kashif, G M and Sagar, Annapoorni Lakshman and Shailaja, G and Ramesh, Arati and Siddavattam, Dayananda} } @article {126686, title = {Using sensitivity analyses to understand bistable system behavior.}, journal = {BMC Bioinformatics}, volume = {24}, year = {2023}, month = {2023 Apr 06}, pages = {136}, abstract = {

BACKGROUND: Bistable systems, i.e., systems that exhibit two stable steady states, are of particular interest in biology. They can implement binary cellular decision making, e.g., in pathways for cellular differentiation and cell cycle regulation. The onset of cancer, prion diseases, and neurodegenerative diseases are known to be associated with malfunctioning bistable systems. Exploring and characterizing parameter spaces in bistable systems, so that they retain or lose bistability, is part of a lot of therapeutic research such as cancer pharmacology.

RESULTS: We use eigenvalue sensitivity analysis and stable state separation sensitivity analysis to understand bistable system behaviors, and to characterize the most sensitive parameters of a bistable system. While eigenvalue sensitivity analysis is an established technique in engineering disciplines, it has not been frequently used to study biological systems. We demonstrate the utility of these approaches on a published bistable system. We also illustrate scalability and generalizability of these methods to larger bistable systems.

CONCLUSIONS: Eigenvalue sensitivity analysis and separation sensitivity analysis prove to be promising tools to define parameter design rules to make switching decisions between either stable steady state of a bistable system and a corresponding monostable state after bifurcation. These rules were applied to the smallest two-component bistable system and results were validated analytically. We showed that with multiple parameter settings of the same bistable system, we can design switching to a desirable state to retain or lose bistability when the most sensitive parameter is varied according to our parameter perturbation recommendations. We propose eigenvalue and stable state separation sensitivity analyses as a framework to evaluate large and complex bistable systems.

}, keywords = {Computational Biology, Models, Biological}, issn = {1471-2105}, doi = {10.1186/s12859-023-05206-2}, author = {Sreedharan, Vandana and Bhalla, Upinder S and Ramakrishnan, Naren} } @article {131285, title = {Validating saliva as a biological sample for cost-effective, rapid and routine screening for SARS-CoV-2}, journal = {INDIAN JOURNAL OF MEDICAL MICROBIOLOGY}, volume = {45}, year = {2023}, month = {09/2023}, abstract = {

Purpose: Compared to nasopharyngeal/oropharyngeal swabs (N/OPS-VTM), non-invasive saliva samples have enormous potential for scalability and routine population screening of SARS-CoV-2. In this study, we investigate the efficacy of saliva samples relative to N/OPS-VTM for use as a direct source for RT-PCR based SARS-CoV-2 detection. Methods: We collected paired nasopharyngeal/oropharyngeal swabs and saliva samples from suspected positive SARS-CoV-2 patients and tested using RT-PCR. We used generalized linear models to investigate factors that explain result agreement. Further, we used simulations to evaluate the effectiveness of saliva-based screening in restricting the spread of infection in a large campus such as an educational institution. Results: We observed a 75.4\% agreement between saliva and N/OPS-VTM, that increased drastically to 83\% in samples stored for less than three days. Such samples processed within two days of collection showed 74.5\% test sensitivity. Our simulations suggest that a test with 75\% sensitivity, but high daily capacity can be very effective in limiting the size of infection clusters in a workspace. Guided by these results, we successfully implemented a saliva-based screening in the Bangalore Life Sciences Cluster (BLiSC) campus. Conclusion: These results suggest that saliva may be a viable alternate source for SARS-CoV-2 surveillance if samples are processed immediately. Although saliva shows slightly lower sensitivity levels when compared to N/ OPS-VTM, saliva collection is logistically advantageous. We strongly recommend the implementation of salivabased screening strategies for large workplaces and in schools, as well as for population-level screening and routine surveillance as we learn to live with the SARS-CoV-2 virus.

}, doi = {10.1016/j.ijmmb.2023.100384}, author = {Ansil, B R and George, Carolin Elizabeth and Chandrasingh, Sindhulina and Viswanathan, Ashwin and Thattai, Mukund and Raghu, Padinjat and Devadiga, Santhosha and Harikumar, Arun Geetha and Harsha, Pulleri Kandi and Nair, Indu and Ramakrishnan, Uma and Mayor, Satyajit} } @article {129165, title = {Vestibular feedback for flight control in hawkmoths.}, journal = {Trends Neurosci}, year = {2023}, month = {2023 May 26}, abstract = {

Flying insects require mechanosensory feedback to rapidly generate compensatory responses to unexpected perturbations. Such feedback is critical in insects such as moths, which fly under low light levels, compromising their ability to visually compensate for aerial perturbations. Here, we describe how diverse mechanosensory organs have adapted to provide vestibular feedback in various insects, with particular focus on hawkmoths.

}, issn = {1878-108X}, doi = {10.1016/j.tins.2023.05.004}, author = {Sane, Sanjay P and Manjunath, Maitri and Mukunda, Chinmayee L} } @article {130545, title = {A view from the President of the Indian Biophysical Society.}, journal = {Biophys Rev}, volume = {15}, year = {2023}, month = {2023 Jun}, pages = {305-306}, abstract = {

This Commentary introduces the readers of Biophysical Reviews to the current president of the Indian Biophysical Society and details a few recent activities of the society in its domestic and international promotion of the biophysics as a scientific discipline.

}, issn = {1867-2450}, doi = {10.1007/s12551-023-01072-7}, author = {Rao, Madan} } @article {133177, title = {Winter foraging ecology of stump-tailed macaques in the Hollongapar Gibbon Sanctuary, Assam, India.}, journal = {J Biosci}, volume = {48}, year = {2023}, month = {2023}, abstract = {

Frugivorous primates in temperate and subtropical regions often experience a shortage or complete absence of fruits for several months of the year. We studied the foraging ecology of a group of stump-tailed macaques in a subtropical forest during winter, when fruit abundance was low. We conducted this study in the Hollongapar Gibbon Sanctuary, Assam, India, from December 2015 to April 2016. We estimated the time-activity budgets, diet, and habitat use of the study troop and also conducted vegetation sampling and phenological monitoring of the study area. The stump-tailed macaque troop spent about 73.2\% of its time foraging and feeding, with seasonal differences in food species intake and in habitat use. Open degraded forests were primarily used in December, January, and February, when the macaques largely fed on shoots of the bamboo and roots of the herb , while they mostly utilised in canopy-covered, degraded forests in March and April. There was a major shift from a primary diet of fruits in the wet season, reported from earlier studies, to possibly relatively poorquality, but abundant, shoots and roots in winter. This suggests that the consumption of these poor-quality fallback food species is a key dietary adaptation of the macaques to periods of fruit scarcity. Although our preliminary study suggests that the feeding behaviour of the stump-tailed macaque in its subtropical semievergreen forest habitat appears to be similar to that of its congeneric species in temperate forests, further investigations are needed to firmly establish the observed foraging patterns of this vulnerable cercopithecine species in its last lowland rainforest refuge in northeastern India.

}, keywords = {Animals, Hylobates, India, Macaca, Macaca arctoides, Seasons}, issn = {0973-7138}, author = {Stotrabhashyam, Swetha and Sharma, Narayan and Kumar, Ajith and Sinha, Anindya} } @article {111547, title = {Active APPL1 sequestration by Plasmodium favors liver-stage development.}, journal = {Cell Rep}, volume = {39}, year = {2022}, month = {2022 May 31}, pages = {110886}, abstract = {

Intracellular pathogens manipulate host cells to survive and thrive. Cellular sensing and signaling pathways are among the key host machineries deregulated to favor infection. In this study, we show that liver-stage Plasmodium parasites compete with the host to sequester a host endosomal-adaptor protein (APPL1) known to regulate signaling in response to endocytosis. The enrichment of APPL1 at the parasitophorous vacuole membrane (PVM) involves an atypical Plasmodium Rab5 isoform (Rab5b). Depletion of host APPL1 alters neither the infection nor parasite development; however, upon overexpression of a GTPase-deficient host Rab5 mutant (hRab5_Q79L), the parasites are smaller and their PVM is stripped of APPL1. Infection with the GTPase-deficient Plasmodium berghei Rab5b mutant (PbRab5b_Q91L) in this case rescues the PVM APPL1 signal and parasite size. In summary, we observe a robust correlation between the level of APPL1 retention at the PVM and parasite size during exoerythrocytic development.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2022.110886}, author = {Lahree, Aparajita and Baptista, Sara de Jesus Santos and Marques, Sofia and Perschin, Veronika and Zuzarte-Lu{\'\i}s, Vanessa and Goel, Manisha and Choudhary, Hadi Hasan and Mishra, Satish and Stigloher, Christian and Zerial, Marino and Sundaramurthy, Varadharajan and Mota, Maria M} } @article {115040, title = {Active emulsions in living cell membranes driven by contractile stresses and transbilayer coupling}, journal = {Proc Natl Acad Sci U S A.}, volume = {119}, year = {2022}, month = {07/2022}, pages = {e2123056119}, abstract = {

The spatiotemporal organization of proteins and lipids on the cell surface has direct functional consequences for signaling, sorting, and endocytosis. Earlier studies have shown that multiple types of membrane proteins, including transmembrane proteins that have cytoplasmic actin binding capacity and lipid-tethered glycosylphosphatidylinositol-anchored proteins (GPI-APs), form nanoscale clusters driven by active contractile flows generated by the actin cortex. To gain insight into the role of lipids in organizing membrane domains in living cells, we study the molecular interactions that promote the actively generated nanoclusters of GPI-APs and transmembrane proteins. This motivates a theoretical description, wherein a combination of active contractile stresses and transbilayer coupling drives the creation of active emulsions, mesoscale liquid order (lo) domains of the GPI-APs and lipids, at temperatures greater than equilibrium lipid phase segregation. To test these ideas, we use spatial imaging of molecular clustering combined with local membrane order, and we demonstrate that mesoscopic domains enriched in nanoclusters of GPI-APs are maintained by cortical actin activity and transbilayer interactions and exhibit significant lipid order, consistent with predictions of the active composite model.

}, doi = {10.1073/pnas.2123056119}, author = {Saha, Suvrajit and Das, A and Patra, C and Anilkumar, AA and Sil, Parijat and Mayor, Satyajit and Rao, Madan} } @article {104421, title = {Active Remodeling of Chromatin and Implications for Folding.}, journal = {J Phys Chem B}, year = {2022}, month = {2021 Dec 24}, abstract = {

Building on the observation that chromatin compaction can be locally modulated by activity, we propose a model of chromatin as an active polymer and study its large scale conformations. In particular, we study an active mechanochemical model of chromosomal folding based on the interplay among polymer elasticity, confinement, topological constraints, and fluctuating active stresses arising from the ATP-dependent action of a variety of chromatin-associated protein machines and chromatin-remodeling proteins and their stochastic turnover. We find that activity drives the chromatin to a nonequilibrium steady state; the statistics of conformations in this nonequilibrium steady state are consistent with recent measurements on intrachromosomal contact probabilities and chromosomal compaction. The contact exponents at steady state show a systematic variation with changes in the nature of activity and the rates of turnover. The steady state configuration of the active chromatin in two dimensions resembles a space-filling Peano curve, which might have implications for the optimization of genome information storage.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.1c08655}, author = {Natesan, Ramakrishnan and Gowrishankar, Kripa and Kuttippurathu, Lakshmi and Kumar, P B Sunil and Rao, Madan} } @article {110442, title = {Active segregation dynamics in the living cell}, journal = {INDIAN JOURNAL OF PHYSICS}, year = {2022}, month = {05/2022}, abstract = {

In this paper, we bring together our efforts in identifying and understanding nonequilibrium phase segregation driven by active processes in the living cell, with special focus on the segregation of cell membrane components driven by active contractile stresses arising from cortical actomyosin. This also has implications for active segregation dynamics in membraneless regions within the cytoplasm and nucleus (3d). We formulate an active version of the Flory-Huggins theory that incorporates a contribution from fluctuating active stresses. Apart from knitting together some of our past theoretical works in a comprehensive narrative, we highlight some new results, and establish a correspondence with recent studies on Active Model B/B+. We point to the many unusual aspects of the dynamics of active phase segregation, such as (i) Anomalous growth dynamics, (ii) Coarsening accompanied by propulsion and coalescence of domains that exhibit non-reciprocal effects, (iii) Segregation into mesoscale domains, (iv) Emergence of a nonequilibrium phase segregated steady state characterised by strong macroscopic fluctuations (fluctuation dominated phase ordering (FDPO)), and (v) Mesoscale segregation even above the equilibrium T-c. Apart from its implications for actively driven segregation of binary fluids, these ideas are at the heart of an Active Emulsion description of the lateral organisation of molecules on the plasma membrane of living cells, whose full molecular elaboration appears elsewhere.

}, doi = {10.1007/s12648-022-02298-z}, author = {Bansal, Ajay and Das, Amit and Rao, Madan} } @article {113527, title = {Acyl chain selection couples the consumption and synthesis of phosphoinositides.}, journal = {EMBO J}, year = {2022}, month = {2022 Jun 30}, pages = {e110038}, abstract = {

Phosphoinositides (PIPn) in mammalian tissues are enriched in the stearoyl/arachidonoyl acyl chain species ("C38:4"), but its functional significance is unclear. We have used metabolic tracers (isotopologues of inositol, glucose and water) to study PIPn synthesis in cell lines in which this enrichment is preserved to differing relative extents. We show that PIs synthesised from glucose are initially enriched in shorter/more saturated acyl chains, but then rapidly remodelled towards the C38:4 species. PIs are also synthesised by a distinct {\textquoteright}re-cycling pathway{\textquoteright}, which utilises existing precursors and exhibits substantial selectivity for the synthesis of C38:4-PA and -PI. This re-cycling pathway is rapidly stimulated during receptor activation of phospholipase-C, both allowing the retention of the C38:4 backbone and the close coupling of PIPn consumption to its resynthesis, thus maintaining pool sizes. These results suggest that one property of the specific acyl chain composition of PIPn is that of a molecular code, to facilitate {\textquoteright}metabolic channelling{\textquoteright} from PIP2 to PI via pools of intermediates (DG, PA and CDP-DG) common to other lipid metabolic pathways.

}, issn = {1460-2075}, doi = {10.15252/embj.2021110038}, author = {Barneda, David and Janardan, Vishnu and Niewczas, Izabella and Collins, Daniel M and Cosulich, Sabina and Clark, Jonathan and Stephens, Len R and Hawkins, Phillip T} } @article {108059, title = {Analysis of Lipid Signaling in Drosophila Photoreceptors using Mass Spectrometry.}, journal = {J Vis Exp}, year = {2022}, month = {2022 Mar 07}, abstract = {

The activation of phospholipase Cβ (PLCβ) is an essential step during sensory transduction in Drosophila photoreceptors. PLCβ activity results in the hydrolysis of the membrane lipid phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] leading ultimately to the activation of transient receptor potential (TRP) and TRP like (TRPL) channels. The activity of PLCβ also leads subsequently to the generation of many lipid species several of which have been proposed to play a role in TRP and TRPL activation. In addition, several classes of lipids have been proposed to play key roles in organizing the cell biology of photoreceptors to optimize signaling reactions for optimal sensory transduction. Historically, these discoveries have been driven by the ability to isolate Drosophila mutants for enzymes that control the levels of specific lipids and perform analysis of photoreceptor physiology in these mutants. More recently, powerful mass spectrometry methods for isolation and quantitative analysis of lipids with high sensitivity and specificity have been developed. These are particularly suited for use in Drosophila where lipid analysis is now possible from photoreceptors without the need for radionuclide labeling. In this article, the conceptual and practical considerations in the use of lipid mass spectrometry for the robust, sensitive, and accurate quantitative assessment of various signaling lipids in Drosophila photoreceptors are covered. Along with existing methods in molecular genetics and physiological analysis such lipid is likely to enhance the power of photoreceptors as a model system for discoveries in biology.

}, issn = {1940-087X}, doi = {10.3791/63516}, author = {Panda, Aniruddha and Thakur, Rajan and Kumari, Aastha and Raghu, Padinjat} } @article {117971, title = {Antelope space-use and behavior indicate multilevel responses to varying anthropogenic influences in a highly human-dominated landscape.}, journal = {Ecol Evol}, volume = {12}, year = {2022}, month = {2022 Oct}, pages = {e9372}, abstract = {

A primary means of conserving a species or a habitat in a human-dominated landscape is through promoting coexistence with humans while minimizing conflict. For this, we should understand how wildlife is impacted by direct and indirect human activities. Such information is rare in areas with high human densities. To investigate how animals respond to altered ecological conditions in human-dominated landscapes, we focused on a wild herbivore of conservation concern in the Krishnasaar Conservation Area (KrCA) in Nepal. Here, blackbuck , a generalist grazer, lives in refugia located with a growing human population. We studied the impacts of humans on habitat use and behavior of blackbuck. We laid 250 {\texttimes} 250 m grid cells in the entire KrCA and carried out indirect sign surveys with three replications for habitat use assessment. We observed herds of blackbuck for 89 h in different habitat types using scan sampling methods. Our habitat-use survey showed that habitats under intensive human use were hardly used by blackbuck, even when high-quality forage was available. Habitat openness was the major predictor of habitat use inside the core area, where levels of human activities were low. We also found a positive correlation between habitat use by blackbuck and livestock. Blackbuck were substantially more vigilant when they were in forest than in grassland, again indicating an influence of risk. Overall, blackbuck appear to be sensitive to the risk associated with both natural and anthropogenic factors. Our findings have direct implications for managing human-wildlife interactions in this landscape, specifically regarding strategies for livestock grazing in habitats highly used by blackbuck and concerning predictions of how changing land use will impact the long-term persistence of blackbuck. Our work suggests that wild herbivores may be able to persist in landscapes with high human densities so long as there are refuges where human activities are relatively low.

}, issn = {2045-7758}, doi = {10.1002/ece3.9372}, author = {Jha, Rohit Raj and Isvaran, Kavita} } @article {117969, title = {AP2 regulates Thickveins trafficking to attenuate NMJ growth signaling in .}, journal = {eNeuro}, year = {2022}, month = {2022 Sep 30}, abstract = {

Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remain poorly understood. Here, we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with Mad, Medea and Dad (components of BMP signaling) to control neuromuscular junction (NMJ) growth in Ultrastructural analysis of mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse. We found that mutations in lead to an accumulation of Tkv receptors at the presynaptic membrane. Interestingly, the level of small GTPase Rab11 was significantly reduced in the mutant synapses. However, expression of Rab11 does not restore the synaptic defects of mutations. We propose a model in which AP2 regulates Tkv internalization and endosomal recycling to control synaptic growth.Understanding the regulation of synaptic development and refinement could provide mechanistic insights into the neural basis of fundamental processes such as learning, memory and adaptation. In this study, we describe the role of σ-adaptin in attenuating NMJ growth signaling and show its involvement in the trafficking of Thickveins receptor at the NMJ. σ-adaptin interacts genetically with the BMP pathway components and NMJ synapses lacking σ-adaptin show reduced levels of the endosomal recycling marker, Rab11. Our study contributes to a broader understanding of AP2 complex-dependent regulation of synaptic growth signaling, which might have implications in neurodevelopment under conditions where endocytosis and trafficking of the BMP receptors are perturbed.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0044-22.2022}, author = {Choudhury, Saumitra Dey and Dwivedi, Manish Kumar and Pippadpally, Srikanth and Patnaik, Abhinandan and Mishra, Shirish and Padinjat, Raghu and Kumar, Vimlesh} } @article {115811, title = {Apis laboriosa confirmed by morphometric and genetic analyses of giant honey bees (Hymenoptera, Apidae) from sites of sympatry in Arunachal Pradesh, North East India}, journal = {APIDOLOGIE}, volume = {53}, year = {2022}, month = {08/2022}, pages = {47}, abstract = {

Two potentially different species of giant honey bees (subgenus Megapis) are endemic to India: Apis dorsata, the widespread low elevation form, and Apis laboriosa of the Pan-Himalayan region. Although they differ morphologically, behaviorally, and genetically, the species status of A. laboriosa remains unresolved. We sampled bees in three widely separated regions of Arunachal Pradesh, North East India, where these two taxa occurred sympatrically. We measured morphological characters of worker bees and conducted principal component analyses of two data sets (size-independent traits and the full set of characters excluding ratios). We also sequenced approximately 500 bp of the mtDNA cytochrome c oxidase subunit I (COI) and generated a phylogenetic tree. In all analyses, A. dorsata and A. laboriosa separated into well-defined groups, and with no bees showing traits suggestive of hybridization, regardless of where the species were collected. The a priori identifications of all specimens based on thoracic hair and abdominal color were verified by the analyses. Our results confirm that A. laboriosa is a valid species.

}, doi = {10.1007/s13592-022-00956-z}, author = {Kitnya, Nyaton and Otis, Gard W. and Chakravorty, Jharna and Smith, Deborah R. and Brockmann, Axel} } @article {105899, title = {Assembling anisotropic colloids using curvature-mediated lipid sorting.}, journal = {Soft Matter}, year = {2022}, month = {2022 Jan 24}, abstract = {

The use of colloid supported lipid bilayers (CSLBs) for assembling colloidal structures has been of recent interest. Here, we use multi-component lipid bilayer membranes formed around anisotropic colloids and show that the curvature anisotropy of the colloids drives a sorting of the lipids in the membrane along the colloids. We then exploit this curvature-sensitive lipid sorting to create "shape-anisotropic patchy colloids" - specifically, we use colloids with six rods sticking out of a central cubic core, "hexapods", for this purpose and demonstrate that membrane patches self-assemble at the tip of each of the six colloidal rods. The membrane patches are rendered sticky using biotinylated lipids in complement with a biotin-binding streptavidin protein. Finally, using these "shape-anisotropic patchy colloids", we demonstrate the directed assembly of colloidal links, paving the way for the creation of heterogeneous and flexible colloidal structures.

}, issn = {1744-6848}, doi = {10.1039/d1sm01517f}, author = {Kumar, Manoj and Singh, Anupam and Del Secco, Benedetta and Baranov, Maksim V and van den Bogaart, Geert and Sacanna, Stefano and Thutupalli, Shashi} } @article {121145, title = {Beyond the passive-active dichotomy: aligning research with the intervention continuum framework of ecological restoration}, journal = {RESTORATION ECOLOGY }, year = {2022}, month = {11/2022}, abstract = {

Experts recommend moving beyond the passive-versus-active dichotomy toward an intervention continuum framework of ecological restoration. Restoration science should guide this transition by elucidating the performance of restoration strategies and underlying mechanisms along gradients of intervention intensity, but is constrained by a paucity of relevant comparisons, conflation of restoration goals, and incomplete documentation of interventions in the present literature. Moving beyond the passive-active dichotomy in restoration science requires emphasis on (1) designing studies that compare multiple restoration treatments to identify whether and how benefits accrue with increasing intervention intensity; (2) distinguishing ecological from other ecosystem restoration goals, as goals could modify outcomes at any given intervention intensity level; and (3) documenting restoration goals, methods, and costs consistently and in sufficient detail in publications, for reproducibility in science and practice, and relevance to comparative and synthetic research, in restoration frameworks based on the intervention continuum.

}, doi = {10.1111/rec.13828}, author = {Krishnan, Aparna and Osuri, Anand M} } @article {116720, title = {Building Indian Biomedical Leadership to Bridge the Gap Between Science, Primary Health Care and Public Health.}, journal = {J Indian Inst Sci}, year = {2022}, month = {2022 Sep 07}, pages = {1-7}, abstract = {

The Indian biomedical landscape has been characterized by the existence of somewhat polarized institutional structures and professional growth. While some scientific and public health challenges have been met with existing structures, there is still a large unmet scientific and public health need. Broadly, the physical separation of science, engineering, medical campuses and industry has led to silos of excellence and accomplishment with huge gaps in innovation and implementation. The lack of inter-disciplinary educational options has further reinforced the cultural underpinning of "guilds" that have found it difficult to collaborate. Strikingly, with almost a comparable number of institutions that train doctors in the allopathic or traditional disciplines such as Ayurveda, Unani etc., an "integrative medicine" framework has not emerged, apart from an over reliance on specialization at the expense of primary care. This paper is written by two physician-scientists, the first is located in a basic life science research center. The second, a practicing family physician, from the institutional anchor of a life sciences research institution. In this, we trace our experiences, primarily from a principal investigator{\textquoteright}s perspective, describing the scientific projects and try to explore the lessons learnt along the way. We will first describe the research in the lab{\textquoteright}s core area of human cervical cancer progression and our more recent effort with Dengue genomics and vaccine design. We then describe the lab{\textquoteright}s engagement with medical campuses and other agencies as well as review our various meetings and interactions so far with our colleagues from Africa to grasp what might be the "generalizable lessons" for the future. The Indian council of medical research initiated a program with Africa in health sciences. Building upon those interactions, we have taken some incremental steps in that direction and described our efforts.

}, issn = {0970-4140}, doi = {10.1007/s41745-022-00320-1}, author = {Krishna, Sudhir and Prasad, Ramakrishna} } @article {111545, title = {Burmagomphus chaukulensis, a new species of dragonfly (Odonata: Anisoptera: Gomphidae) from the Western Ghats, Maharashtra, India}, journal = {ZOOTAXA }, volume = {5133}, year = {2022}, month = {05/2022}, pages = {413-430}, abstract = {

We describe a new species of dragonfly, Burmagomphus chaukulensis sp. nov., based on four males and two females from Chaukul, Sindhudurg, Maharashtra located in the Western Ghats biodiversity hotspot of India. The newly described species is diagnosed from its congeners by a combination of following characters: the shape of male caudal appendages (prominent lateral spines on cerci) and the lateral thoracic markings (stripe on mesepisternum reduced and pointed anteriorly). Additionally, B. chaukulensis is unique in terms of the shape of hamuli, strongly angulated with spines at both sides. An updated identification key to Indian Burmagomphus spp. is also provided.

}, doi = {10.11646/zootaxa.5133.3.6}, author = {Joshi, Shantanu and Sawant, Dattaprasad and Ogale, Hemant and Kunte, Krushnamegh} } @article {115043, title = {Ca2+ imaging of self and other in medial prefrontal cortex during social dominance interactions in a tube test.}, journal = {Proc Natl Acad Sci U S A}, volume = {119}, year = {2022}, month = {08/2022}, pages = {e2107942119}, abstract = {

The study of social dominance interactions between animals offers a window onto the decision-making involved in establishing dominance hierarchies and an opportunity to examine changes in social behavior observed in certain neurogenetic disorders. Competitive social interactions, such as in the widely used tube test, reflect this decision-making. Previous studies have focused on the different patterns of behavior seen in the dominant and submissive animal, neural correlates of effortful behavior believed to mediate the outcome of such encounters, and interbrain correlations of neural activity. Using a rigorous mutual information criterion, we now report that neural responses recorded with endoscopic calcium imaging in the prelimbic zone of the medial prefrontal cortex show unique correlations to specific dominance-related behaviors. Interanimal analyses revealed cell/behavior correlations that are primarily with an animal{\textquoteright}s own behavior or with the other animal{\textquoteright}s behavior, or the coincident behavior of both animals (such as pushing by one and resisting by the other). The comparison of unique and coincident cells helps to disentangle cell firing that reflects an animal{\textquoteright}s own or the other{\textquoteright}s specific behavior from situations reflecting conjoint action. These correlates point to a more cognitive rather than a solely behavioral dimension of social interactions that needs to be considered in the design of neurobiological studies of social behavior. These could prove useful in studies of disorders affecting social recognition and social engagement, and the treatment of disorders of social interaction.

}, doi = {10.1073/pnas.2107942119 }, author = {Garcia-Font, N and Mitchell-Heggs, R and Saxena, K and Gabbert, C and Taylor, G and Mastroberadino, G and Spooner, PA and Gobbo, F and Dabrowska, JK and Chattarji, S and Kind, PC and Schultz, S.R. and Morris, RGM} } @article {103917, title = {Carcass Scavenging Relaxes Chemical-Driven Female Interference Competition in Flour Beetles}, journal = {AMERICAN NATURALIST}, year = {2022}, month = {01/2022}, abstract = {

Female-female nonsexual interference competition is a major fitness determinant of biased sex ratio groups with high female density. What strategies can females use to overcome the negative impact of this competition? To answer this question we used flour beetles (Tribolium castaneum) where competing females from female-biased groups were already known to suppress each other{\textquoteright}s fecundity by secreting toxic quinones from their stink glands, indicating a unique chemical-driven interference competition. Surprisingly, increasing resources did not alleviate these fitness costs. Females also did not disperse more from the site of interference competition. Hence, the competition was influenced by neither the total resource availability nor the lack of opportunity to avoid chemical interference. Instead, protein sequestered via scavenging of nutrient-rich carcasses relaxed female competition by increasing fecundity and reducing the quinone content. Finally, stink gland components themselves triggered carcass scavenging and increased fecundity, indicating the possibility of a novel chemical-driven feedback loop to reduce the competition. In the present work we provide the rare analyses where multiple competing hypotheses were jointly tested to establish carcass scavenging as an important potential strategy to overcome the fitness costs of intrasexual female interference competition.

}, doi = {10.1086/717250}, author = {Bagchi, Basabi and Seal, Srijan and Raina, Manasven and Basu, Dipendra Nath and Khan, Imroze} } @article {106149, title = {Career challenges for young independent researchers in India}, journal = {CURRENT SCIENCE}, volume = {122}, year = {2022}, month = {01/2022}, pages = {135-143}, abstract = {

The scientific enterprise in India has grown dramatically in the past few decades, with research emerging as a viable and important career option for students of science. The country thus has a large population of young scientists in the early stages of establishing their independent research careers. While this demographic is arguably the most important group that will determine the future of scientific research in India, their status and concerns are poorly understood. The Indian National Young Academy of Sciences conducted a national survey to better understand and present the challenges faced by them. Through a structured questionnaire, we sought the views of researchers below 45 years of age. Here, we summarize the responses from 854 participants across multiple early career stages. We highlight key challenges faced by these scientists in establishing an independent research career, and suggest steps to address them.

}, doi = {10.18520/cs/v122/i2/135-143}, author = {Agashe, Deepa and Maheshwary, Sugandha and Pattanaik, Jitendra Kumar and Prakash, Jai and Bhatt, Pragya and Arya, S. S. and Chatterjee, Sriparna and Kumar, Pankaj and Singh, Paramdeep and Abbas, Nazia and Sharma, Chandra Shekhar and Chaudhuri, Chirasree Roy and Devi, Pooja} } @article {118431, title = {Chasms in charismatic species research: Seventy years of carnivore science and its implications for conservation and policy in India}, journal = {BIOLOGICAL CONSERVATION }, volume = {273}, year = {2022}, month = {09/2022}, abstract = {

Substantial research and conservation resources are invested towards studying, protecting, and managing carnivore populations, globally. But scholarly investigations that link the outcomes of ecological research and their applications are not commonplace. Such syntheses can have implications for large predator management and human well-being. India holds strategic importance for carnivore conservation and management, supporting 60 species (including two sub-species), at relatively high densities. Reviewing all carnivore studies published in post-independence India (1947-2020), we investigate the academic impacts of published journal articles, and the role of institutions and collaborative research. We then present an analysis of the thematic patterns, trends, and biases in carnivore research. Using multiple case studies, we discuss the pertinence of ecological research in shaping litigation, policy, and conservation, while also deliberating on the facilitative role of funding and bureaucracy. Despite their purported charisma, not all carnivores benefited from extensive ecological studies, nor did conservation policy adequately draw from available scientific information; research studies were skewed towards large felids, and litigation/policies were overwhelmingly shaped by one species, the Bengal tiger Panthera tigris. We argue for reorienting current research efforts through increased focus on lesser-known species, adopting best practices in socio-ecological studies, widening the ambit of interdisciplinary work, democratizing carnivore science through partnerships, and enhancing synergy between carnivore researchers and research groups. Considered together, we believe this paper can serve as a guide for planning future research, for amplifying the overall profile of carnivore conservation science, and may be adapted across tropical countries of the Global South.

}, doi = {10.1016/j.biocon.2022.109694}, author = {Srivathsa, Arjun and Banerjee, Aditya and Banerjee, Soumya and Chawla, Malaika Mathew and Das, Anshita and Ganguly, Divyajyoti and Rodrigues, Ryan G. and Adhya, Tiasa and Bhatia, Saloni and Kshettry, Aritra and Majgaonkar, Iravatee and Punjabi, Girish A. and Puri, Mahi and Singh, Priya and Surve, Nikit} } @article {116708, title = {Chronic browsing by an introduced mammalian herbivore in a tropical island alters species composition and functional traits of forest understory plant communities}, journal = {BIOTROPICA }, year = {2022}, month = {08/2022}, abstract = {

Mammalian herbivores have large-scale impacts on vegetation, altering structure, and species composition, especially in tropical grasslands and savannas. However, there is limited understanding of the potential impacts of mammalian herbivores in tropical wet forests, where they are typically less abundant. We investigated the effects of an introduced mammalian herbivore chital (Axis axis) on vegetation structure, composition and leaf functional traits of tropical evergreen forests of the Andaman Islands, India. Across seven islands, representing a gradient of herbivore densities, increasing chital presence was associated with decreased understory richness, understory density and adult tree richness, but was not related to adult tree density or size class distributions. We also found a significant decrease in community level leaf palatability traits (specific leaf area decreased and leaf thickness increased) with increasing chital habitat use. This community level shift in leaf trait values was better explained by intraspecific variation in leaf traits across islands rather than changes in species composition. In summary, we show persistent long-term impacts of an introduced mammalian herbivore on understory tropical tree communities although there is little impact on adult tree communities. Our results also show that functional traits of species can be altered in response to novel herbivory, even at herbivore densities where there are no detectable impacts on adult forest structure or composition. Such altered functional traits may potentially alter ecosystem functioning in these forests even without changes in vegetation structure. Abstract in Hindi is available with online material.

}, doi = {10.1111/btp.13149}, author = {Anujan, Krishna and Ratnam, Jayashree and Sankaran, Mahesh} } @article {115011, title = {Combining hypothesis- and data-driven neuroscience modeling in FAIR workflows.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 07 06}, abstract = {

Modeling in neuroscience occurs at the intersection of different points of view and approaches. Typically, hypothesis-driven modeling brings a question into focus so that a model is constructed to investigate a specific hypothesis about how the system works or why certain phenomena are observed. Data-driven modeling, on the other hand, follows a more unbiased approach, with model construction informed by the computationally intensive use of data. At the same time, researchers employ models at different biological scales and at different levels of abstraction. Combining these models while validating them against experimental data increases understanding of the multiscale brain. However, a lack of interoperability, transparency, and reusability of both models and the workflows used to construct them creates barriers for the integration of models representing different biological scales and built using different modeling philosophies. We argue that the same imperatives that drive resources and policy for data - such as the FAIR (Findable, Accessible, Interoperable, Reusable) principles - also support the integration of different modeling approaches. The FAIR principles require that data be shared in formats that are Findable, Accessible, Interoperable, and Reusable. Applying these principles to models and modeling workflows, as well as the data used to constrain and validate them, would allow researchers to find, reuse, question, validate, and extend published models, regardless of whether they are implemented phenomenologically or mechanistically, as a few equations or as a multiscale, hierarchical system. To illustrate these ideas, we use a classical synaptic plasticity model, the Bienenstock-Cooper-Munro rule, as an example due to its long history, different levels of abstraction, and implementation at many scales.

}, keywords = {Neurosciences, Workflow}, issn = {2050-084X}, doi = {10.7554/eLife.69013}, author = {Eriksson, Olivia and Bhalla, Upinder Singh and Blackwell, Kim T and Crook, Sharon M and Keller, Daniel and Kramer, Andrei and Linne, Marja-Leena and Saudargiene, Ausra and Wade, Rebecca C and Hellgren Kotaleski, Jeanette} } @article {110789, title = {Comparison of methods for estimating density and population trends for low-density Asian bears}, journal = {GLOBAL ECOLOGY AND CONSERVATION}, volume = {35}, year = {2022}, month = {06/2022}, abstract = {

Populations of bears in Asia are vulnerable to extinction and effective monitoring is critical to measure and direct conservation efforts. Population abundance (local density) or growth (lambda) are the most sensitive metrics to change. We discuss the value in implementing spatially explicit capture-recapture (SCR), the current gold standard for density estimation, and open population SCR (OPSCR) to monitor changes in density over time. We provide guidance for designing studies to provide estimates with sufficient power to detect changes. Because of the wide availability of camera traps and interest in their use, we consider six density estimation methods and their extensions developed for use with camera traps, with specific consideration of assumptions and applications for monitoring Asian bears. We conducted a power analysis to calculate the precision in estimates needed to detect changes in populations with reference to IUCN Red List criteria. We performed a systematic review of empirical studies implementing camera trap abundance estimation methods and considered sample sizes, effort, and model assumptions required to achieve adequate precision for population monitoring. We found SCR and OPSCR, reliant on "marked" individuals, are currently the only methods with enough power to reliably detect even moderate to major (20-80\%) declines. Camera trap methods with unmarked individuals rarely achieved precision sufficient to detect even large declines (80-90\%), although with some exceptions (e.g., situations with moderate population densities, large number of sampling sites, or inclusion of ancillary local telemetry data. We describe additional estimation options including line transects, direct observations, monitoring age-specific survival and reproductive rates, and hybrid/integrated methodologies that may have potential to work for some Asian bear populations. We conclude monitoring changes in abundance or density is possible for most Asian bear populations but will require collaboration among researchers over broad spatial extents and extensive financial investment to overcome biological and logistical constraints. We strongly encourage practitioners to consider study design and sampling effort required to meet objectives by conducting simulations, power analyses, and assumption checks prior to implementing monitoring efforts, and reporting standardized dispersion measures such as coefficients of variation to allow for assessment of precision. Our guidance is relevant to other low-density and wide-ranging species.

}, doi = {10.1016/j.gecco.2022.e02058}, author = {Morin, Dana J. and Boulanger, John and Bischof, Richard and Lee, David C. and Ngoprasert, Dusit and Fuller, Angela K. and McLellan, Bruce and Steinmetz, Robert and Sharma, Sandeep and Garshelis, Dave and Gopalaswamy, Arjun and Nawaz, Muhammad Ali and Karanth, Ullas} } @article {115027, title = {Computational analysis of potential candidate genes involved in the cold stress response of ten Rosaceae members.}, journal = {BMC Genomics}, volume = {23}, year = {2022}, month = {2022 Jul 16}, pages = {516}, abstract = {

BACKGROUND: Plant species from Rosaceae family are economically important. One of the major environmental factors impacting those species is cold stress. Although several Rosaceae plant genomes have recently been sequenced, there have been very few research conducted on cold upregulated genes and their promoter binding sites. In this study, we used computational approaches to identify and analyse potential cold stress response genes across ten Rosaceae family members.

RESULTS: Cold stress upregulated gene data from apple and strawberry were used to identify syntelogs in other Rosaceae species. Gene duplication analysis was carried out to better understand the distribution of these syntelog genes in different Rosaceae members. A total of 11,145 popular abiotic stress transcription factor-binding sites were identified in the upstream region of these potential cold-responsive genes, which were subsequently categorised into distinct transcription factor (TF) classes. MYB classes of transcription factor binding site (TFBS) were abundant, followed by bHLH, WRKY, and AP2/ERF. TFBS patterns in the promoter regions were compared among these species and gene families, found to be quite different even amongst functionally related syntelogs. A case study on important cold stress responsive transcription factor family, AP2/ERF showed less conservation in TFBS patterns in the promoter regions. This indicates that syntelogs from the same group may be comparable at the gene level but not at the level of cis-regulatory elements. Therefore, for such genes from the same family, different repertoire of TFs could be recruited for regulation and expression. Duplication events must have played a significant role in the similarity of TFBS patterns amongst few syntelogs of closely related species.

CONCLUSIONS: Our study overall suggests that, despite being from the same gene family, different combinations of TFs may play a role in their regulation and expression. The findings of this study will provide information about potential genes involved in the cold stress response, which will aid future functional research of these gene families involved in many important biological processes.

}, keywords = {Cold-Shock Response, Gene Expression Regulation, Plant, Multigene Family, Phylogeny, Plant Proteins, Rosaceae, Stress, Physiological, Transcription Factors}, issn = {1471-2164}, doi = {10.1186/s12864-022-08751-x}, author = {Shafi, K Mohamed and Sowdhamini, Ramanathan} } @article {118723, title = {Computational tools to study RNA-protein complexes.}, journal = {Front Mol Biosci}, volume = {9}, year = {2022}, month = {2022}, pages = {954926}, abstract = {

RNA is the key player in many cellular processes such as signal transduction, replication, transport, cell division, transcription, and translation. These diverse functions are accomplished through interactions of RNA with proteins. However, protein-RNA interactions are still poorly derstood in contrast to protein-protein and protein-DNA interactions. This knowledge gap can be attributed to the limited availability of protein-RNA structures along with the experimental difficulties in studying these complexes. Recent progress in computational resources has expanded the number of tools available for studying protein-RNA interactions at various molecular levels. These include tools for predicting interacting residues from primary sequences, modelling of protein-RNA complexes, predicting hotspots in these complexes and insights into derstanding in the dynamics of their interactions. Each of these tools has its strengths and limitations, which makes it significant to select an optimal approach for the question of interest. Here we present a mini review of computational tools to study different aspects of protein-RNA interactions, with focus on overall application, development of the field and the future perspectives.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.954926}, author = {Bheemireddy, Sneha and Sandhya, Sankaran and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan} } @article {108394, title = {Contrasting Effects of Grazing vs Browsing Herbivores Determine Changes in Soil Fertility in an East African Savanna}, journal = {ECOSYSTEMS }, year = {2022}, month = {03/2022}, abstract = {

We used a long-term herbivore removal experiment where paired exclosure-open treatments were established at the Mpala Research Centre, Laikipia, Kenya, in 1999 to examine changes in soil nitrogen (N) at nutrient-rich glades and adjacent nutrient-poor bushland sites after almost two decades of herbivore removal. Glades in this landscape are created by large inputs of dung and urine from previous long-term corralling of cattle in an otherwise nutrient-poor matrix of woodland (bushland). We predicted (1) a net gain of soil nutrients at bushland sites (that is, inputs of nutrients \> losses) and (2) a net loss of soil nutrients at glade sites (that is, inputs of nutrients \< losses) following herbivore exclusion. As expected, soil N increased (by 28\% after 17 years) with herbivore removal, but remained largely unchanged in the presence of herbivores at low-nutrient bushland sites. However, contrary to our expectations, soil total N in nutrient-rich glades also increased (+ 18\%) when herbivores were removed, but declined when grazed (- 11\%). Although the underlying mechanisms are unclear, we suggest that increased N fixation by Acacia spp., combined with increased canopy cover and associated tree leaf litter, resulted in elevated soil N following browser removal in low-nutrient bushland sites, while grazer-induced increases in the rate of N transformations between organic and mineral forms resulted in a more "open" N cycle (as evidenced by higher N mineralization rates and foliar N), with increased potential for N loss in gaseous forms, in grazed nutrient-rich glade sites. Grazers and browsers thus appear to affect the N cycle and create and reinforce heterogeneity in unique ways.

}, doi = {10.1007/s10021-022-00748-7}, author = {Coetsee, C. and Wigley, B. J. and Sankaran, M. and Ratnam, J. and Augustine, D. J.} } @article {99928, title = {The costs and benefits of basal infection resistance vs immune priming responses in an insect.}, journal = {Dev Comp Immunol}, volume = {126}, year = {2022}, month = {2021 Sep 16}, pages = {104261}, abstract = {

In insects, basal pathogen resistance and immune priming can evolve as mutually exclusive strategies, with distinct infection outcomes. However, the evolutionary drivers of such diverse immune functions remain poorly understood. Here, we addressed this key issue by systematically analyzing the differential fitness costs and benefits of priming vs resistance evolution in Tribolium beetle populations infected with Bacillus thuringiensis. Surprisingly, resistant beetles had increased post-infection reproduction and a longer lifespan under both starving as well as fed conditions, with no other measurable costs. In contrast, priming reduced offspring early survival, development rate and reproduction. Priming did improve post-infection survival of offspring, but this added trans-generational benefit of immune priming might not compensate for its pervasive costs. Resistance was thus consistently more beneficial. Overall, our work demonstrates the evolutionary change in trans-generational priming response, and provides a detailed comparison of the complex fitness consequences of evolved priming vs resistance.

}, issn = {1879-0089}, doi = {10.1016/j.dci.2021.104261}, author = {Prakash, Arun and Agashe, Deepa and Khan, Imroze} } @article {112955, title = {Cultivar-specific miRNA-mediated RNA silencing in grapes.}, journal = {Planta}, volume = {256}, year = {2022}, month = {2022 Jun 23}, pages = {17}, abstract = {

MAIN CONCLUSION: In-depth comparative degradome analysis of two domesticated grape cultivars with diverse secondary metabolite accumulation reveals differential miRNA-mediated targeting. Small (s)RNAs such as micro(mi)RNAs and secondary small interfering (si) often work as negative switches of gene expression. In plants, it is well known that miRNAs target and cleave mRNAs that have high sequence complementarity. However, it is not known if there are variations in miRNA-mediated targeting between subspecies and cultivars that have been subjected to vast genetic modifications through breeding and other selections. Here, we have used PAREsnip2 tool for analysis of degradome datasets derived from two contrasting domesticated grape cultivars having varied fruit color, habit and leaf shape. We identified several interesting variations in sRNA targeting using degradome and 5{\textquoteright}RACE analysis between two contrasting grape cultivars that was further correlated using RNA-seq analysis. Several of the differences we identified are associated with secondary metabolic pathways. We propose possible means by which sRNAs might contribute to diversity in secondary metabolites and other development pathways between two domesticated cultivars of grapes.

}, keywords = {Gene Expression Regulation, Plant, MicroRNAs, Plant Breeding, RNA Interference, RNA, Plant, Sequence Analysis, RNA, Vitis}, issn = {1432-2048}, doi = {10.1007/s00425-022-03934-y}, author = {Tirumalai, Varsha and Narjala, Anushree and Swetha, Chenna and G Vivek Hari Sundar and Sujith, T N and Shivaprasad, P V} } @article {105897, title = {Cx3Cr1-Cre induction leads to microglial activation and IFN-1 signaling caused by DNA damage in early postnatal brain.}, journal = {Cell Rep}, volume = {38}, year = {2022}, month = {2022 Jan 18}, pages = {110252}, abstract = {

Cx3cr1-driven Cre recombinase (Cre) is a widely used genetic tool for enabling gene manipulation in microglia and macrophages. However, an in-depth analysis of the possible detrimental effects of Cre activity in microglia, surprisingly, remains missing. Here, we demonstrate an age-dependent sensitivity of microglia to Cx3cr1-Cre toxicity, wherein Cre induction, specifically in early postnatal microglia, is detrimental to microglial development, proliferation, and function. Tamoxifen (TAM)-induced Cre activity leads to microglial activation, type 1 interferon (IFN-1) signaling, and increased phagocytosis, causing aberrant synaptic pruning during the early postnatal period and anxious behavior at later age. The detrimental effects of Cre induction are caused by DNA-damage-induced toxicity in microglia and are limited to the early postnatal period, showing no detrimental effects in adult microglia. Thus, our study reveals an age-dependent vulnerability of microglia to Cre activity, thereby highlighting age dependency of Cre action, which could be especially applicable in the broader context of environment-responsive cell types.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2021.110252}, author = {Sahasrabuddhe, Vinaya and Ghosh, HS} } @article {109307, title = {DarkCideS 1.0, a global database for bats in karsts and caves.}, journal = {Sci Data}, volume = {9}, year = {2022}, month = {2022 Apr 05}, pages = {155}, abstract = {

Understanding biodiversity patterns as well as drivers of population declines, and range losses provides crucial baselines for monitoring and conservation. However, the information needed to evaluate such trends remains unstandardised and sparsely available for many taxonomic groups and habitats, including the cave-dwelling bats and cave ecosystems. We developed the DarkCideS 1.0 ( https://darkcides.org/ ), a global database of bat caves and species synthesised from publicly available information and datasets. The DarkCideS 1.0 is by far the largest database for cave-dwelling bats, which contains information for geographical location, ecological status, species traits, and parasites and hyperparasites for 679 bat species are known to occur in caves or use caves in part of their life histories. The database currently contains 6746 georeferenced occurrences for 402 cave-dwelling bat species from 2002 cave sites in 46 countries and 12 terrestrial biomes. The database has been developed to be collaborative and open-access, allowing continuous data-sharing among the community of bat researchers and conservation biologists to advance bat research and comparative monitoring and prioritisation for conservation.

}, keywords = {Animals, Biodiversity, Chiroptera, Ecosystem}, issn = {2052-4463}, doi = {10.1038/s41597-022-01234-4}, author = {Tanalgo, Krizler C and Tabora, John Aries G and de Oliveira, Hernani Fernandes Magalh{\~a}es and Haelewaters, Danny and Beranek, Chad T and Ot{\'a}lora-Ardila, A{\'\i}da and Bernard, Enrico and Gon{\c c}alves, Fernando and Eriksson, Alan and Donnelly, Melissa and Gonz{\'a}lez, Joel Monz{\'o}n and Ramos, Humberto Fern{\'a}ndez and Rivas, Alberto Clark and Webala, Paul W and Deleva, Stanimira and Dalhoumi, Ridha and Maula, Jaycelle and Lizarro, Dennis and Aguirre, Luis F and Bouillard, Nils and Quibod, Ma Ni{\~n}a Regina M and Barros, Jennifer and Turcios-Casco, Manfredo Alejandro and Mart{\'\i}nez, Marcio and Ordo{\~n}ez-Mazier, Diego Iv{\'a}n and Orellana, Jos{\'e} Alejandro Soler and Ordo{\~n}ez-Trejo, Eduardo J and Ordo{\~n}ez, Danny and Chornelia, Ada and Lu, Jian Mei and Xing, Chen and Baniya, Sanjeev and Muylaert, Renata L and Dias-Silva, Leonardo Henrique and Ruadreo, Nittaya and Hughes, Alice Catherine} } @article {116719, title = {DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria.}, journal = {J Cell Biol}, volume = {221}, year = {2022}, month = {2022 Oct 03}, abstract = {

Mitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for the distribution, segregation, and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organization for mtDNA maintenance, the impact of mtDNA perturbations on mitochondrial dynamics remains less understood. Here, we develop a tool to induce mitochondria-specific DNA damage using a mitochondrial-targeted base modifying bacterial toxin, DarT. Following damage, we observe dynamic reorganization of mitochondrial networks, likely driven by mitochondrial dysfunction. Changes in the organization are associated with the loss of mtDNA, independent of mitophagy. Unexpectedly, perturbation to exonuclease function of mtDNA replicative polymerase, Mip1, results in rapid loss of mtDNA. Our data suggest that, under damage, partitioning of defective mtDNA and organelle are de-coupled, with emphasis on mitochondrial segregation independent of its DNA. Together, our work underscores the importance of genome maintenance on mitochondrial function, which can act as a modulator of organelle organization and segregation.

}, issn = {1540-8140}, doi = {10.1083/jcb.202205104}, author = {Dua, Nitish and Seshadri, Akshaya and Badrinarayanan, Anjana} } @article {110447, title = {DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration.}, journal = {Dev Biol}, year = {2022}, month = {2022 May 03}, abstract = {

Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputation-induced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.

}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2022.04.011}, author = {Sarkar, Souradeep R and Dubey, Vinay Kumar and Jahagirdar, Anusha and Lakshmanan, Vairavan and Haroon, Mohamed Mohamed and Sowndarya, Sai and Sowdhamini, Ramanathan and Palakodeti, Dasaradhi} } @article {116727, title = {Dealing with Environmental Fluctuations: Diversity of Potassium Uptake Systems Across the Three Domains of Life}, journal = {JOURNAL OF PLANT GROWTH REGULATION }, year = {2022}, month = {09/2022}, abstract = {

Potassium ion (K+) constitutes one of the six macronutrients and is implicated in several processes that aid cell survival and growth. Optimal intracellular K+ level is achieved through the combination of low and high-affinity transport systems allowing uptake over a wide range (millimolar (mM) to micromolar (mu M)) of external K+ concentration and is impacted by both biotic and abiotic stress conditions. Plants growing in K+-deficient soil are more susceptible to disease and damage caused due to abiotic stress factors like frost, drought, and salinity. The severity decreases with an increase in exogenous K+. Exposure to high saline conditions results in an increase in intracellular sodium (Na+) and a concurrent decrease in K+ levels. Thus, intracellular K+ levels are crucially linked to specific uptake and efflux mechanisms operational during a particular stress regime. While molecular pathway(s) operative in K+-mediated endurance to multiple stress conditions are not fully understood, studies suggest a positive correlation between capacity for incremented K+ levels and survival advantages. In this article we review: K+ uptake systems and mechanisms available across life domains with special reference to plant systems. Recent emerging evidence on the involvement of K+ in stress management, and the role of K+ uptake systems during pathogenicity and symbiotic associations. Approaches aimed at optimizing intracellular K+ levels through modulation of (influx and efflux mechanisms) and (vacuole pools) as a viable strategy to support plant growth under stress conditions.

}, doi = {10.1007/s00344-022-10782-3}, author = {Rajagopal, Divya and Sopory, Sudhir K. and Mathew, M. K.} } @article {108402, title = {Decoding the Mechanism of Specific RNA Targeting by Ribosomal Methyltransferases.}, journal = {ACS Chem Biol}, year = {2022}, month = {2022 Mar 22}, abstract = {

Methylation of specific nucleotides is integral for ribosomal biogenesis and also serves as a common mechanism to confer antibiotic resistance by pathogenic bacteria. Here, by determining the high-resolution structure of the 30S-KsgA complex by cryo-electron microscopy, a state was captured, where KsgA juxtaposes between helices h44 and h45 of the 30S ribosome, separating them, thereby enabling remodeling of the surrounded rRNA and allowing the cognate site to enter the methylation pocket. With the structure as a guide, several mutant versions of the ribosomes, where interacting bases in the catalytic helix h45 and surrounding helices h44, h24, and h27, were mutated and evaluated for their methylation efficiency revealing factors that direct the enzyme to its cognate site with high fidelity. The biochemical studies show that the three-dimensional environment of the ribosome enables the interaction of select loop regions in KsgA with the ribosome helices paramount to maintain selectivity.

}, issn = {1554-8937}, doi = {10.1021/acschembio.1c00732}, author = {Singh, Juhi and Raina, Rahul and Vinothkumar, Kutti R and Anand, Ruchi} } @article {112948, title = {Defects and metric anomalies in Foppl-von Karman surfaces}, journal = {PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES}, volume = {478}, year = {2022}, month = {06/2022}, pages = {20210829}, abstract = {

A general framework is developed to study the deformation and stress response in Foppl-von Karman shallow shells for a given distribution of defects, such as dislocations, disclinations and interstitials, and metric anomalies, such as thermal and growth strains. The theory includes dislocations and disclinations whose defect lines can both pierce the two-dimensional surface and lie within the surface. An essential aspect of the theory is the derivation of strain incompatibility relations for stretching and bending strains with incompatibility sources in terms of the various defect and metric anomaly densities. The incompatibility relations are combined with balance laws and constitutive assumptions to obtain the inhomogeneous Foppl-von Karman equations for shallow shells. Several boundary value problems are posed, and solved numerically, by first considering only dislocations and then disclinations coupled with growth strains.

}, doi = {10.1098/rspa.2021.0829}, author = {Singh, Manish and Roychowdhury, Ayan and Gupta, Anurag} } @article {105482, title = {Degradome comparison between wild and cultivated rice identifies differential targeting by miRNAs.}, journal = {BMC Genomics}, volume = {23}, year = {2022}, month = {2022 Jan 14}, pages = {53}, abstract = {

BACKGROUND: Small non-coding (s)RNAs are involved in the negative regulation of gene expression, playing critical roles in genome integrity, development and metabolic pathways. Targeting of RNAs by ribonucleoprotein complexes of sRNAs bound to Argonaute (AGO) proteins results in cleaved RNAs having precise and predictable\ 5{\textquoteleft} ends. While tools to study sliced bits of RNAs to confirm the efficiency of sRNA-mediated regulation are available, they are sub-optimal. In this study, we provide an improvised version of a tool with better efficiency to accurately validate sRNA targets.

RESULTS: Here, we improvised the CleaveLand tool to identify additional micro (mi)RNA targets that belong to the same family and also other targets within a specified free energy cut-off. These additional targets were otherwise excluded during the default run. We employed these tools to understand the sRNA targeting efficiency in wild and cultivated rice, sequenced degradome from two rice lines, O. nivara and O. sativa indica Pusa Basmati-1 and analyzed variations in sRNA targeting. Our results indicate the existence of multiple miRNA-mediated targeting differences between domesticated and wild species. For example, Os5NG4 was targeted only in wild rice that might be responsible for the poor secondary wall formation when compared to cultivated rice. We also identified differential mRNA targets of secondary sRNAs that were generated after miRNA-mediated cleavage of primary targets.

CONCLUSIONS: We identified many differentially targeted mRNAs between wild and domesticated rice lines. In addition to providing a step-wise guide to generate and analyze degradome datasets, we showed how domestication altered sRNA-mediated cascade silencing during the evolution of indica rice.

}, keywords = {Argonaute Proteins, Base Sequence, MicroRNAs, Oryza, RNA, Messenger}, issn = {1471-2164}, doi = {10.1186/s12864-021-08288-5}, author = {Swetha, Chenna and Narjala, Anushree and Pandit, Awadhesh and Tirumalai, Varsha and Shivaprasad, P V} } @article {104895, title = {The delusion of stripes: A century-old mystery of five-lined sun skinks (Reptilia: Scincidae: Eutropis) of Peninsular India elucidated}, journal = {Zoologischer Anzeiger}, volume = {296}, year = {2022}, month = {01/2022}, pages = {71-90}, abstract = {

We re-evaluate the taxonomic identities of five-lined skinks of the genus Eutropis (E.\ trivittata, E. beddomei, E. nagarjunensis, and E.\ bibronii) inhabiting the Indian subcontinent. Previously it has been considered that E.\ trivittata is distributed in the western India and E. dissimilis in the northern India (from north-eastern India up to Pakistan). Based on our analysis, we revealed that the illustration (iconotype) of the untraceable type specimen of E. trivittata depicted by Hardwicke in Gray (1834) from {\textquotedblleft}Dumdum{\textquotedblright} near Kolkata, West Bengal matches the typical E. dissimilis, also described from {\textquotedblleft}Bengal{\textquotedblright}. The senior synonym, E. trivittata is a morphologically unique species, which is also supported by divergence in the mitochondrial 12S and 16S regions. E. trivittata is clearly separated with divergences of 5{\textendash}7\% from E. beddomei, E. vertebralis and E. nagarjunensis for 16S rRNA. After placing E.\ dissimilis with the synonymy of E.\ trivittata, the taxonomic status of the western Indian {\textquoteleft}E.\ trivittata{\textquoteright} required to be clarified. Therefore, we resurrect Mabuia vertebralis Boulenger, 1887, a junior synonym of western Indian E. trivittata, and redescribe its holotype collected from {\textquotedblleft}Belgaum{\textquotedblright}, Karnataka. Although, morphologically closest to E. beddomei, Eutropis vertebralis comb. nov. is a sister taxon to E. nagarjunensis with divergence of 4\% in the same mitochondrial regions. Based on our update of the currently confirmed localities for E. vertebralis comb. nov. and E. trivittata, we conducted a Species Distribution Modelling (SDM) using the Maximum Entropy algorithm to predict their distribution range, and we discuss their conservation status.

}, doi = {10.1016/j.jcz.2021.11.004}, author = {Amarasinghe, AA Thasun and Ganesh, S.R. and Mirza, Zeeshan A and Campbell, Patrick D. and Pauwels, Olivier S.G. and Schweiger, Silke and Kupfer, Alexander and Patel, Harshil and Karunarathna, Suranjan and Deuti, Kaushik and Ineich, Ivan and Hallermann, Jakob and Abinawanto, A. and Supriatna, Jatna} } @article {112947, title = {Detecting and removing sample contamination in phylogenomic data: an example and its implications for Cicadidae phylogeny (Insecta: Hemiptera).}, journal = {Syst Biol}, year = {2022}, month = {2022 Jun 16}, abstract = {

Contamination of a genetic sample with DNA from one or more non-target species is a continuing concern of molecular phylogenetic studies, both Sanger sequencing studies and Next-Generation Sequencing (NGS) studies. We developed an automated pipeline for identifying and excluding likely cross-contaminated loci based on detection of bimodal distributions of patristic distances across gene trees. When the contamination occurs between samples within a dataset, comparisons between a contaminated sample and its contaminant taxon will yield bimodal distributions with one peak close to zero patristic distance. This new method does not rely on a priori knowledge of taxon relatedness nor does it determine the causes(s) of the contamination. Exclusion of putatively contaminated loci from a dataset generated for the insect family Cicadidae showed that these sequences were affecting some topological patterns and branch supports, although the effects were sometimes subtle, with some contamination-influenced relationships exhibiting strong bootstrap support. Long tip branches and outlier values for one anchored phylogenomic pipeline statistic (AvgNHomologs) were correlated with the presence of contamination. While the AHE markers used here, which target hemipteroid taxa, proved effective in resolving deep and shallow level Cicadidae relationships in aggregate, individual markers contained inadequate phylogenetic signal, in part probably due to short length. The cleaned dataset, consisting of 429 loci, from 90 genera representing 44 of 56 current Cicadidae tribes, supported three of the four sampled Cicadidae subfamilies in concatenated-matrix maximum likelihood (ML) and multispecies coalescent-based species tree analyses, with the fourth subfamily weakly supported in the ML trees. No well-supported patterns from previous family-level Sanger sequencing studies of Cicadidae phylogeny were contradicted. One taxon (Aragualna plenalinea) did not fall with its current subfamily in the genetic tree, and this genus and its tribe Aragualnini is reclassified to Tibicininae following morphological re-examination. Only subtle differences were observed in trees after removal of loci for which divergent base frequencies were detected. Greater success may be achieved by increased taxon sampling and developing a probe set targeting a more recent common ancestor and longer loci. Searches for contamination are an essential step in phylogenomic analyses of all kinds and our pipeline is an effective solution.

}, issn = {1076-836X}, doi = {10.1093/sysbio/syac043}, author = {Owen, Christopher L and Marshall, David C and Wade, Elizabeth J and Meister, Russ and Goemans, Geert and Kunte, Krushnamegh and Moulds, Max and Hill, Kathy and Villet, M and Pham, Thai-Hong and Kortyna, Michelle and Lemmon, Emily Moriarty and Lemmon, Alan R and Simon, Chris} } @article {118405, title = {Development of a Systematic Strategy toward Promotion of α-Synuclein Aggregation Using 2-Hydroxyisophthalamide-Based Systems. }, journal = {Biochemistry}, year = {2022}, month = {10/2022}, abstract = {

Establishing a potent scheme against α-synuclein aggregation involved in Parkinson{\textquoteright}s disease has been evaluated as a promising route to identify compounds that either inhibit or promote the aggregation process of α-synuclein. In the last two decades, this perspective has guided a dramatic increase in the efforts, focused on developing potent drugs either for retardation or promotion of the self-assembly process of α-synuclein. To address this issue, using a chemical kinetics platform, we developed a strategy that enabled a progressively detailed analysis of the molecular events leading to protein aggregation at the microscopic level in the presence of a recently synthesized 2-hydroxyisophthalamide class of small organic molecules based on their binding affinity. Furthermore, qualitatively, we have developed a strategy of disintegration of α-synuclein fibrils in the presence of these organic molecules. Finally, we have shown that these organic molecules effectively suppress the toxicity of α-synuclein oligomers in neuron cells.

}, doi = {10.1021/acs.biochem.2c00371}, author = {Uddin, A and Malla, J A and Kumar, H and Kumari, M and Sinha, S and Sharma, VK and Kumar, Y and Talukdar, P and Lahiri, M and Maiti, TK and Hazra, P} } @article {109309, title = {Development of candidate gene-based markers and map-based cloning of a dominant rust resistance gene in cultivated groundnut (Arachis hypogaea L.).}, journal = {Gene}, volume = {827}, year = {2022}, month = {2022 Apr 04}, pages = {146474}, abstract = {

A dominant rust resistance gene, VG 9514-Rgene was isolated through map-based cloning. Sequence analysis revealed non-synonymous mutations in the TIR, NBS and LRR region of the R-protein. Candidate gene-based markers from these SNPs revealed complete co-segregation of the isolated VG 9514-Rgene with rust resistance in a RIL population and confirmed their map position in between FRS 72 and SSR_GO340445 markers in arahy03 chromosome. Blastp search of VG 9514-Rprotein detected Arahy.T6DCA5 with \>80.0\% identity that localized at 142,544,745.0.142,549,184 in arahy03 chromosome. K/K calculation revealed that VG 9514-Rgene had undergone positive selection compared to four homologous genes in the groundnut genome. Homology based structure modelling of this R-protein revealed a typical consensus three-dimensional folding of TIR-NBS-LRR protein. Non-synonymous mutations in susceptible version of R-protein were mapped and found E268Q mutation in hhGRExE motif, Y309F in RNBS-A motif and I579T in MHD motif of NB-ARC domain are probable candidates for loss of function.

}, issn = {1879-0038}, doi = {10.1016/j.gene.2022.146474}, author = {Mondal, Suvendu and Mohamed Shafi, K and Raizada, Avi and Song, Hui and Badigannavar, Anand M and Sowdhamini, Ramanathan} } @article {104419, title = {Differential tolerance capacity of intertidal organisms (sponge and zoanthid) to the environmental stresses: Preliminary Bndings from a rockpool transplantation experiment}, journal = {JOURNAL OF EARTH SYSTEM SCIENCE}, volume = {131}, year = {2022}, month = {03/2022}, abstract = {

Marine intertidal organisms face extreme environmental fluctuations due to tidal cycles. To investigate the impact of environmental changes (high salinity, sea surface temperature, and anthropogenic pollution) on the health of the coastal area, we selected the dominant intertidal organisms: sponge (Cinachyrella cf. cavernosa) and zoanthid (Zoanthus sansibaricus) as our model system from a rocky beach Anjuna, Goa, India. Sponges and zoanthids were transplanted from their natural habitat (mid-tide pools) to new habitat (upper-tide pools). The study was carried out for 15 days when these pools experienced flushing during the first and last 5 days (high tide was \>1.8 m) and no flushing during the middle 5 days (high tide was \<1.8 m). The indices of physiological response (such as in budding activity and oscular openings) in the sponge and (chlorophyll estimation and symbiotic zooxanthellae count) in zoanthid were estimated at natural and transplanted habitats. Upper intertidal pools experienced intense temperature (29.9-36.15 degrees C), salinity (35.03-46.7 ppt) and variability in dissolved oxygen (3.2-9.5 mg/l). The transplanted sponge did show the closure of oscula (90.62\%) and reduction in buds (40-94.9\%), but they could survive beyond 15 days. While transplanted zoanthid showed bleaching and did not survive beyond 72 h due to reduced chlorophyll content (up to 44.21\%) and zooxanthellae count (34.54\%). Our results depicted the differential tolerance capacity of sessile organisms like sponge and zoanthid to environmental changes, which govern the vertical zonation in the rocky intertidal region. It highlights the role of these sessile invertebrates as early indicators of environmental changes.

}, doi = {10.1007/s12040-021-01739-3}, author = {Singh, Anshika and Thakur, Narsinh L. and Sheikh, Farhan} } @article {120166, title = {Differentiating between the sequence of structural events on alternative pathways of folding of a heterodimeric protein.}, journal = {Protein Sci}, year = {2022}, month = {2022 Nov 16}, pages = {e4513}, abstract = {

Distinguishing between competing pathways of folding of a protein, on the basis of how they differ in their progress of structure acquisition, remains an important challenge in protein folding studies. A previous study had shown that the heterodimeric protein, double chain monellin (dcMN) switches between alternative folding pathways upon a change in guanidine hydrochloride (GdnHCl) concentration. In the current study, the folding of dcMN has been characterized by the pulsed hydrogen exchange (HX) labelling methodology used in conjunction with mass spectrometry. Quantification of the extent to which folding intermediates accumulate and then disappear with time of folding at both low and high GdnHCl concentrations, where the folding pathways are known to be different, shows that the folding mechanism is describable by a triangular three-state mechanism. Structural characterization of the productive folding intermediates populated on the alternative pathways has enabled the pathways to be differentiated on the basis of the progress of structure acquisition that occurs on them. The intermediates on the two pathways differ in the extent to which the α-helix and the rest of the β-sheet have acquired structure that is protective against HX. The major difference is, however, that β2 has not acquired any protective structure in the intermediate formed on one pathway, but it has acquired significant protective structure in the intermediate formed on the alternative pathway. Hence the sequence of structural events is different on the two alternative pathways. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.4513}, author = {Bhattacharjee, Rupam and Udgaonkar, Jayant B} } @article {119607, title = {The diversity of protein-protein interaction interfaces within T=3 icosahedral viral capsids}, journal = {Front Mol Biosci. }, volume = {9:967877}, year = {2022}, month = {10/2022}, abstract = {

Some non-enveloped virus capsids assemble from multiple copies of a single type of coat-protein (CP). The comparative energetics of the diverse CP-CP interfaces present in such capsids likely govern virus assembly-disassembly mechanisms. The T = 3 icosahedral capsids comprise 180 CP copies arranged about two-, three-, five- and six-fold axes of (quasi-)rotation symmetry. Structurally diverse CPs can assemble into T = 3 capsids. Specifically, the Leviviridae CPs are structurally distinct from the Bromoviridae, Tombusviridae and Tymoviridae CPs which fold into the classic "jelly-roll" fold. However, capsids from across the four families are known to disassemble into dimers. To understand whether the overall symmetry of the capsid or the structural details of the CP determine virus assembly-disassembly mechanisms, we analyze the different CP-CP interfaces that occur in the four virus families. Previous work studied protein homodimer interfaces using interface size (relative to the monomer) and hydrophobicity. Here, we analyze all CP-CP interfaces using these two parameters and find that the dimerization interface (present between two CPs congruent through a two-fold axis of rotation) has a larger relative size in the Leviviridae than in the other viruses. The relative sizes of the other Leviviridae interfaces and all the jelly-roll interfaces are similar. However, the dimerization interfaces across families have slightly higher hydrophobicity, potentially making them stronger than other interfaces. Finally, although the CP-monomers of the jelly-roll viruses are structurally similar, differences in their dimerization interfaces leads to varied dimer flexibility. Overall, differences in CP-structures may induce different modes of swelling and assembly-disassembly in the T = 3 viruses.

}, doi = {10.3389/fmolb.2022.967877}, author = {Prakash, DL and Gosavi, Shachi} } @article {105475, title = {Diversity of Sodium Transporter HKT1;5 in Genus Oryza}, journal = {RICE SCIENCE}, volume = {29}, year = {2022}, month = {01/2022}, pages = {31-46}, abstract = {

Asian cultivated rice shows allelic variation in sodium transporter, OsHKT1;5, correlating with shoot sodium exclusion (salinity tolerance). These changes map to intra/extracellularly-oriented loops that occur between four transmembrane-P loop-transmembrane (MPM) motifs in OsHKT1;5. HKT1;5 sequences from more recently evolved Oryza species (O. sativa/O. officinalis complex species) contain two expansions that involve two intracellularly oriented loops/helical regions between MPM domains, potentially governing transport characteristics, while more ancestral HKT1;5 sequences have shorter intracellular loops. We compared homology models for homoeologous OcHKT1;5-K and OcHKT1;5-L from halophytic O. coarctata to identify complementary amino acid residues in OcHKT1;5-L that potentially enhance affinity for Na+. Using haplotyping, we showed that Asian cultivated rice accessions only have a fraction of HKT1;5 diversity available in progenitor wild rice species (O. nivara and O. rufipogon). Progenitor HKT1;5 haplotypes can thus be used as novel potential donors for enhancing cultivated rice salinity tolerance. Within Asian rice accessions, 10 non-synonymous HKT1;5 haplotypic groups occur. More HKT1;5 haplotypic diversities occur in cultivated indica gene pool compared to japonica. Predominant Haplotypes 2 and 10 occur in mutually exclusive japonica and indica groups, corresponding to haplotypes in O. sativa salt-sensitive and salt-tolerant landraces, respectively. This distinct haplotype partitioning may have originated in separate ancestral gene pools of indica and japonica, or from different haplotypes selected during domestication. Predominance of specific HKT1;5 haplotypes within the 3 000 rice dataset may relate to eco-physiological fitness in specific geo-climatic and/or edaphic contexts.

}, doi = {10.1016/j.rsci.2021.12.003}, author = {Pulipati, Shalini and Somasundaram, Suji and Rana, Nitika and Kumaresan, Kavitha and Shafi, Mohamed and Civan, Peter and Sellamuthu, Gothandapani and Jaganathan, Deepa and Ramaravi, Prasanna Venkatesan and Punitha, S. and Raju, Kalaimani and Mantri, Shrikant S. and Sowdhamini, R. and Parida, Ajay and Venkataraman, Gayatri} } @article {115813, title = {Double DJ-1 domain containing Arabidopsis DJ-1D is a robust macromolecule deglycase.}, journal = {New Phytol}, year = {2022}, month = {2022 Jul 31}, abstract = {

Plants, being sessile, are prone to genotoxin-induced macromolecule damage. Among the inevitable damaging agents are reactive carbonyls that induce glycation of DNA, RNA and proteins to result in the build-up of advanced glycated end-products. However, it is unclear how plants repair glycated macromolecules. DJ-1/PARK7 members are a highly conserved family of moonlighting proteins having double domains in higher plants and single domains in other phyla. Here we show that Arabidopsis DJ-1D offers robust tolerance to endogenous and exogenous stresses through its ability to repair glycated DNA, RNA and proteins. DJ-1D also reduced the formation of reactive carbonyls through its efficient methylglyoxalase activity. Strikingly, full-length double domain-containing DJ-1D suppressed the formation of advanced glycated end-products in yeast and plants. DJ-1D also efficiently repaired glycated nucleic acids and nucleotides in vitro and mitochondrial DNA in vivo under stress, indicating the existence of a new DNA repair pathway in plants. We propose that multi-stress responding plant DJ-1 members, often present in multiple copies among plants, probably contributed to the adaptation to a variety of endogenous and exogenous stresses.

}, issn = {1469-8137}, doi = {10.1111/nph.18414}, author = {Prasad, Melvin and Kataria, Priyanka and Ningaraju, Sunayana and Buddidathi, Radhika and Bankapalli, Kondalarao and Swetha, Chenna and Susarla, Gautam and Venkatesan, Radhika and D{\textquoteright}Silva, Patrick and Shivaprasad, Padubidri V} } @article {131287, title = {Draft genome sequence of an invasive plant .}, journal = {Bioinformation}, volume = {18}, year = {2022}, month = {2022}, pages = {739-741}, abstract = {

L. is an invasive species of global concern. An ornamental plant originating from central America, it has now spread across natural and human-dominated habitats across tropical and subtropical regions globally. Understanding the population and evolutionary genetics of this species could help gain deeper insights into invasion biology, and provide tools for more effective management. Such investigation would require a relatively good quality genome assembly. While there have been reports of a transcriptome, it has been challenging to construct the genome assembly because of the large genome size. We present here the first draft genome assembly of L. which has an N50 value of 62 Kb, genome completeness of 99.3\% and genome coverage of 74.3\%. We hope that such an assembly will help researchers study colonization history, the genetic basis of adaptation and invasiveness, and help design strategies to contain the invasiveness of this plant, allowing biodiversity recovery in several parts of the globe.

}, issn = {0973-2063}, doi = {10.6026/97320630018739}, author = {Joshi, Adwait G and Praveen, P and Ramakrishnan, Uma and Sowdhamini, Ramanathan} } @article {108048, title = {A DROSOPHILA CIRCUIT FOR HABITUATION OVERRIDE.}, journal = {J Neurosci}, year = {2022}, month = {2022 Feb 25}, abstract = {

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Here we analyze how exposure to a novel stimulus causes override of gustatory (proboscis-extension reflex or "PER") habituation. While brief sucrose contact with tarsal hairs causes na{\"\i}ve to extend their proboscis, persistent exposure reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief thermogenetic activation of a population of TH (Tyrosine-Hydroxylase) positive neurons, a subset of which send projections to the subesophagial zone (SEZ). Significantly, sensory-neuron induced habituation override requires transmitter release from these TH-positive cells. Treatments that cause override specifically influence the habituated state, with no effect on the na{\"\i}ve sucrose response across a range of concentrations. Taken together with other findings, these observations in female flies are consistent with a model in which novel taste stimuli trigger activity in dopaminergic neurons which, directly or indirectly, inhibit GABAergic cells that drive PER habituation. The implications of these findings for general mechanisms of attentional and sensory override of habituation are discussed.Habituation can be overcome when a new context requires an enhanced response to a familiar stimulus. However, the underlying mechanisms remain incompletely understood. Previous studies have provided evidence that habituation of the sucrose-induced proboscis extension reflex (PER) in Drosophila occurs through potentiation of inhibition onto the PER pathway. This work defines controlled protocols for override of PER habituation and uses them to outline the underlying circuit mechanisms. The results presented support a model in which novel taste stimuli cause dishabituation by activating a subset of tyrosine-hydroxylase-expressing neurons that inhibit GABAergic neurons whose potentiation underlies PER habituation. At a general level, these findings further highlight a central role for inhibition and disinhibition in the control of behavioral flexibility.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.1842-21.2022}, author = {Trisal, Swati and Aranha, Marcia and Chodankar, Ankita and VijayRaghavan, K and Ramaswami, Mani} } @article {108045, title = {DSDBASE 2.0: updated version of DiSulphide dataBASE, a database on disulphide bonds in proteins.}, journal = {Database (Oxford)}, volume = {2022}, year = {2022}, month = {2022 Mar 01}, abstract = {

Disulphide bonds are stabilizing crosslinks in proteins and serve to enhance their thermal stability. In proteins that are small and rich in disulphide bonds, they could be the major determining factor for the choice of conformational state since their constraints on appropriate backbone conformation can be substantial. Such crosslinks and their positional conservation could itself enable protein family and functional association. Despite the importance of the field, there is no comprehensive database on disulphide crosslinks that is available to the public. Herein we provide information on disulphides in DSDBASE2.0, an updated and significantly expanded database that is freely available, fully annotated and manually curated database on native and modelled disulphides. The web interface also provides several useful computational tools that have been specifically developed for proteins containing disulphide crosslinks. The modelling of disulphide crosslinks is performed using stereochemical criteria, coded within our Modelling of Disulphides in Proteins (MODIP) algorithm. The inclusion of modelled disulphides potentially enhances the loop database substantially, thereby permitting the recognition of compatible polypeptide segments that could serve as templates for immediate modelling. The DSDBASE2.0 database has been updated to include 153,944 PDB entries, 216,096 native and 20,153,850 modelled disulphide bond segments from PDB January 2021 release. The current database also provides a resource to user-friendly search for multiple disulphide bond containing loops, along with annotation of their function using GO and subcellular localization of the query. Furthermore, it is possible to obtain the three-dimensional models of disulphide-rich small proteins using an independent algorithm, RANMOD, that generates and examines random, but allowed backbone conformations of the polypeptide. DSDBASE2.0 still remains the largest open-access repository that organizes all disulphide bonds of proteins on a single platform. The database can be accessed from http://caps.ncbs.res.in/dsdbase2.

}, issn = {1758-0463}, doi = {10.1093/database/baac005}, author = {Kalmankar, Neha V and Pavalam, Murugavel and Indrakumar, Sowmya and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan} } @article {105474, title = {Ecological monitoring and indicator taxa: butterfly communities in heterogeneous landscapes of the Western Ghats and Malabar coast, India}, journal = {JOURNAL OF INSECT CONSERVATION}, year = {2022}, month = {01/2022}, abstract = {

As the pace of socioeconomic developments continues to accelerate, the environmental degradation and biodiversity loss become the norm. While it is crucial to constantly monitor and assess ecological impacts, baseline data are scanty for ecologically sensitive regions and biodiversity hotspots such as the Western Ghats. With their great public appeal and ease to work with, butterflies are excellent communities to monitor the ecological health. To characterize the baseline patterns of butterfly communities, using time-constrained counts, we surveyed eight heterogeneous landscapes of the coastal plains of the Western Ghats. We recorded 43,118 individuals and 175 species, with large differences in their diversity and species-specific abundances among habitats. The coastal and semi-evergreen-forest habitats were at the two extremes with intermediate patterns in agricultural and other habitats that suffered diverse anthropogenic pressures. Using indicator value analysis, 22 habitat-specific and several shared indicator species were identified. Even some of the most abundant species showed distinct niches, and therefore can be used as indicator species to monitor community dynamics. Patterns of numerous habitat-specific host-plant butterfly species pairs that were identified were discussed in relation to butterfly abundance and conservation. Implications for insect conservation This study has implications for insect conservation by providing important baseline data on butterfly taxa for future monitoring and assessment of this ecologically sensitive region.

}, doi = {10.1007/s10841-022-00368-5}, author = {Naik, Deepak and Rao, R. Shyama Prasad and Kunte, Krushnamegh and Mustak, Mohammed S.} } @article {106549, title = {Editorial: Advances in Molecular Docking and Structure-Based Modelling.}, journal = {Front Mol Biosci}, volume = {9}, year = {2022}, month = {2022}, pages = {839826}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.839826}, author = {Rebehmed, Joseph and de Brevern, Alexandre G and Sowdhamini, Ramanathan and Joseph, Agnel Praveen} } @article {111899, title = {Effect of Altitude on Volatile Organic and Phenolic Compounds of Artemisia brevifolia Wall ex Dc. From the Western Himalayas}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, volume = {10}, year = {2022}, month = {06/2022}, abstract = {

Adaptation to changing environmental conditions is a driver of plant diversification. Elevational gradients offer a unique opportunity for investigating adaptation to a range of climatic conditions. The use of specialized metabolites as volatile and phenolic compounds is a major adaptation in plants, affecting their reproductive success and survival by attracting pollinators and protecting themselves from herbivores and other stressors. The wormseed Artemisia brevifolia can be found across multiple elevations in the Western Himalayas, a region that is considered a biodiversity hotspot and is highly impacted by climate change. This study aims at understanding the volatile and phenolic compounds produced by A. brevifolia in the high elevation cold deserts of the Western Himalayas with the view to understanding the survival strategies employed by plants under harsh conditions. Across four sampling sites with different elevations, polydimethylsiloxane (PDMS) sampling and subsequent GCMS analyses showed that the total number of volatile compounds in the plant headspace increased with elevation and that this trend was largely driven by an increase in compounds with low volatility, which might improve the plant{\textquoteright}s resilience to abiotic stress. HPLC analyses showed no effect of elevation on the total number of phenolic compounds detected in both young and mature leaves. However, the concentration of the majority of phenolic compounds decreased with elevation. As the production of phenolic defense compounds is a costly trait, plants at higher elevations might face a trade-off between energy expenditure and protecting themselves from herbivores. This study can therefore help us understand how plants adjust secondary metabolite production to cope with harsh environments and reveal the climate adaptability of such species in highly threatened regions of our planet such as the Himalayas.

}, doi = {10.3389/fevo.2022.864728}, author = {Nataraj, Nandita and Hussain, Manzoor and Ibrahim, Mohd and Hausmann, Alexander E. and Rao, Srinivas and Kaur, Satwinderjeet and Khazir, Jabeena and Mir, Bilal Ahmad and Olsson, Shannon B.} } @article {118434, title = {Effects of a plant cyclotide on conformational dynamics and destabilization of β-amyloid fibrils through molecular dynamics simulations.}, journal = {Front Mol Biosci}, volume = {9}, year = {2022}, month = {2022}, pages = {986704}, abstract = {

Aggregation of β-amyloid (Aβ) peptide is one of the hallmarks of Alzheimer{\textquoteright}s disease (AD) which results in chronic and progressive neurodegeneration of the brain. A recent study by our group have shown the ability of cyclic disulfide-rich peptides ("cyclotides") isolated from a medicinal plant, , to inhibit the aggregation of Aβ peptides and reduce oxidative stress caused by reactive oxygen species using models of transgenic . In the present study, through extensive computational docking and multi-ns molecular dynamics (MD) simulation, we evaluated if cyclotides can stably bind to Aβ molecules and/or destabilize the Aβ fibril by preventing conformational changes from α-helical to β-sheet rich structures. We demonstrate that cyclotides bind effectively and stably to different forms of Aβ structures hydrogen bonding and hydrophobic interactions. One of the conserved hydrophobic interface residues, Tyr10 was mutated to Ala and the impact of this virtual mutation was estimated by additional MD simulations for the wild-type (WT) and mutant protein-peptide complexes. A detailed MD simulation analyses revealed that cyclotides form hydrogen bonds with the toxic amyloid assemblies thereby weakening the inter-strand hydrogen bonds between the Aβ peptide. The φ-ѱ distribution map of residues in the cyclotide binding pocket that ideally adopt β-sheet conformation show deviation towards right-handed ɑ-helical (ɑ) conformation. This effect was similar to that observed for the Tyr10Ala mutant and doubly so, for the cyclotide bound form. It is therefore possible to hypothesise that the opening up of amyloid β-sheet is due to an unfolding process occurring in the Aβ caused by cyclotide binding and inhibition. Our current findings provide novel structural insights on the mode of interaction between cyclotides and Aβ fibrils and describe their anti-amyloid aggregation potential. This sheds light on the future of cyclotide-based drug design against protein aggregation, a hallmark event in many neurodegenerative diseases.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.986704}, author = {Kalmankar, Neha V and Gehi, Bhuvaneshwari Rajendrakumar and Sowdhamini, Ramanathan} } @article {128573, title = {eLife{\textquoteright}s new model and its impact on science communication.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 Dec 08}, abstract = {

The eLife Early-Career Advisory Group discusses eLife{\textquoteright}s new peer review and publishing model, and how the whole process of scientific communication could be improved for the benefit of early-career researchers and the entire scientific community.

}, keywords = {Communication, Peer Review}, issn = {2050-084X}, doi = {10.7554/eLife.84816}, author = {Urban, Lara and De Niz, Mariana and Fern{\'a}ndez-Chiappe, Florencia and Ebrahimi, Hedyeh and Han, Laura K M and Mehta, Devang and Mencia, Regina and Mittal, Divyansh and Ochola, Elizabeth and Paz Quezada, Carolina and Romani, Facundo and Sinapayen, Lana and Tay, Andy and Varma, Aalok and Yahia Mohamed Elkheir, Lamis} } @article {110446, title = {Elongation of Fibrils Formed by a Tau Fragment is Inhibited by a Transient Dimeric Intermediate.}, journal = {J Phys Chem B}, year = {2022}, month = {2022 May 03}, abstract = {

The formation and propagation of aggregates of the tau protein in the brain are associated with the tauopathy group of neurodegenerative diseases. Different tauopathies have been shown to be associated with structurally distinct aggregates of tau. However, the mechanism by which different structural folds arise remains poorly understood. In this study of fibril formation by the fragment tau-K18 of tau, it is shown that the Lys 280 {\textrightarrow} Glu mutation in the variant tau-K18 K280E forms fibrils that are morphologically distinct from those formed by wild-type (wt) tau-K18. The mutant fibrils appear to have two protofilaments twisted around each other, whereas the wt fibrils are straight and appear to have a single protofilament. Modeling the kinetics of seeded aggregation, using a simple Michaelis-Menten-like mechanism, reveals that the two morphologically distinct fibrils are elongated with different catalytic efficiencies. Surprisingly, when the elongation of monomeric tau-K18 is seeded with tau-K18 K280E fibrils, it is seen to be inhibited at high monomer concentrations. Such inhibition is not seen when elongation is seeded with tau-K18 fibrils. The mechanism of inhibition is shown to be describable as uncompetitive inhibition, in which a transient dimeric form of tau-K18 acts as an uncompetitive inhibitor. Importantly, a dimeric form of tau-K18 is seen to be populated to a detectable extent early during aggregation. A covalently linked tau dimer, with an inter-molecular disulphide linkage, is shown to be capable of acting as an inhibitor. In summary, a quantitative kinetic approach has provided an understanding of how the formation of distinct structural folds of tau fibrils can be modulated by mutation and how the elongation of one fibril type, but not the other, is inhibited by a transiently formed dimer.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.1c10752}, author = {Kumar, Harish and Udgaonkar, Jayant B} } @article {116184, title = {Environment-dependent benefits of interindividual variation in honey bee recruitment}, journal = {ANIMAL BEHAVIOUR}, volume = {192}, year = {2022}, month = {10/2022}, pages = {9-26}, abstract = {

Interindividual differences in behaviour within the members of a social group can affect the group{\textquoteright}s productivity. In eusocial insects, individual differences between workers in a colony play a central role in division of labour and task allocation. Extensive empirical and theoretical work has highlighted variation in response thresholds as a proximate mechanism underlying individual behavioural differences and hence division of labour. However, other response parameters, like response probability and intensity, can also affect these differences. In this study, we first extended a previously published agent-based model on honey bee, Apis mellifera, foraging to understand the relative importance of response (dance) probability and response (dance) intensity in the task of recruitment. Comparing variation obtained from the simulations with previously published empirical data, we found that response intensity played a more important role than probability in producing consistent interindividual differences in recruitment behaviour. We then explored the benefits provided by this individual variation in recruitment behaviour to the colony{\textquoteright}s collective foraging effort under different environmental conditions. We found that individual variation led to a greater energy yield per forager, but only when food was abundant. Our study highlights the need to consider all response parameters while studying division of labour and adds to the growing body of evidence linking individual variation in behavioural responses to the success of social groups. (C) 2022 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

}, doi = {10.1016/j.anbehav.2022.07.011}, author = {Rajagopal, Supraja and Brockmann, Axel and George, Ebi Antony} } @article {118432, title = {Evolutionarily conserved proline residues impede the misfolding of the mouse prion protein by destabilizing an aggregation-competent partially unfolded form }, journal = {J Mol Biol.}, year = {2022}, month = {10/2022}, abstract = {

The misfolding of the prion protein has been linked to several neurodegenerative diseases. Despite extensive studies, the mechanism of the misfolding process remains poorly understood. The present study structurally delineates the role of the conserved proline residues present in the structured C-terminal domain of the mouse prion protein (moPrP) in the misfolding process. It is shown that mutation of these Pro residues to Ala leads to destabilization of the native (N) state, and also to rapid misfolding. Using hydrogen-deuterium exchange (HDX) studies coupled with mass spectrometry (MS), it has been shown that the N state of moPrP is in rapid equilibrium with a partially unfolded form (PUF2*) at pH 4. It has been shown that the Pro to Ala mutations make PUF2* energetically more accessible from the N state by stabilizing it relative to the unfolded (U) state. The apparent rate constant of misfolding is found to be linearly proportional to the extent to which PUF2* is populated in equilibrium with the N state, strongly indicating that misfolding commences from PUF2*. It has also been shown that the Pro residues restrict the boundary of the structural core of the misfolded oligomers. Overall, this study highlights how the conserved proline residues control misfolding of the prion protein by modulating the stability of the partially unfolded form from which misfolding commences.

}, doi = {10.1016/j.jmb.2022.167854 }, author = {Pal, S. and Udgaonkar, Jayant B} } @article {105477, title = {The evolutionary history of an accidental model organism, the leopard gecko Eublepharis macularius (Squamata: Eublepharidae).}, journal = {Mol Phylogenet Evol}, year = {2022}, month = {2022 Jan 12}, pages = {107414}, abstract = {

The leopard gecko, Eublepharis macularius, is a widely used model organism in laboratory and experimental studies. The high phenotypic diversity in the pet trade, the fact that the provenance of different breeding lines is unknown, and that distinct Eublepharis species are known to hybridize, implies that the continued use of E. macularius as a model requires clarity on the origin of the lineages in the pet trade. We combine multi-locus sequence data and the first range-wide sampling of the genus Eublepharis to reconstruct the evolutionary history of the Eublepharidae and Eublepharis, with an updated time-tree for the Eublepharidae. Our sampling includes five of the six recognized species and additional nominal taxa of uncertain status comprising 43 samples from 34 localities plus 48 pet-trade samples. The Eublepharidae began diversifying in the Cretaceous. Eublepharis split from its sister genera in Africa in the Palaeocene-Eocene, and began diversifying in the Oligocene-Miocene, with late Miocene-Pliocene cladogenesis giving rise to extant species. The current species diversity within this group is moderately underestimated. Our species delimitation suggests 10 species with four potentially unnamed divergent lineages in Iran, India and Pakistan. All 30 individuals of E. macularius that we sampled from the pet trade, which include diverse morphotypes, come from a few shallow E. macularius clades, confirming that lab and pet trade strains are part of a single taxon. One of the wild-caught haplotypes of E. macularius, from near Karachi, Pakistan, is identical to (10) pet-trade samples and all other captive populations are closely related to wild-caught animals from central/southern Pakistan (0.1-0.5 \% minimum pairwise uncorrected ND2 sequence divergence).

}, issn = {1095-9513}, doi = {10.1016/j.ympev.2022.107414}, author = {Agarwal, Ishan and Bauer, Aaron M and Gamble, Tony and Giri, Varad B and Jablonski, Daniel and Khandekar, Akshay and Mohapatra, Pratyush P and Masroor, Rafaqat and Mishra, Anurag and Ramakrishnan, Uma} } @article {110791, title = {Evolutionary jumps in bacterial GC content.}, journal = {G3 (Bethesda)}, year = {2022}, month = {2022 May 17}, abstract = {

Genomic GC content is a fundamental molecular trait linked with many key genomic features such as codon and amino acid use. Across bacteria, GC content is surprisingly diverse and has been studied for many decades; yet its evolution remains incompletely understood. Since it is difficult to observe GC content evolve on laboratory time-scales, phylogenetic comparative approaches are instrumental; but this dimension is rarely studied systematically in the case of bacterial GC content. We applied phylogenetic comparative models to analyse GC content evolution in multiple bacterial groups across two major bacterial phyla. We find that GC content diversifies via a combination of gradual evolution and evolutionary "jumps". Surprisingly, unlike prior reports that solely focused on reductions in GC, we found a comparable number of jumps with both increased and decreased GC content. Overall, many of the identified jumps occur in lineages beyond the well-studied peculiar examples of endosymbiotic and AT-rich marine bacteria, and do not support the predicted role of oxygen dependence. Our analysis of rapid and large shifts in GC content thus identifies new clades and novel contexts to further understand the ecological and evolutionary drivers of this important genomic trait.

}, issn = {2160-1836}, doi = {10.1093/g3journal/jkac108}, author = {Mahajan, Saurabh and Agashe, Deepa} } @article {115259, title = {Exploring the medicinally important secondary metabolites landscape through the lens of transcriptome data in fenugreek (Trigonella foenum graecum L.).}, journal = {Sci Rep}, volume = {12}, year = {2022}, month = {2022 Aug 08}, pages = {13534}, abstract = {

Fenugreek (Trigonella foenum-graecum L.) is a self-pollinated leguminous crop belonging to the Fabaceae family. It is a multipurpose crop used as herb, spice, vegetable and forage. It is a traditional medicinal plant in India attributed with several nutritional and medicinal properties including antidiabetic and anticancer. We have performed a combined transcriptome assembly from RNA sequencing data derived from leaf, stem and root tissues. Around 209,831 transcripts were deciphered from the assembly of 92\% completeness and an N50 of 1382 bases. Whilst secondary metabolites of medicinal value, such as trigonelline, diosgenin, 4-hydroxyisoleucine and quercetin, are distributed in several tissues, we report transcripts that bear sequence signatures of enzymes involved in the biosynthesis of such metabolites and are highly expressed in leaves, stem and roots. One of the antidiabetic alkaloid, trigonelline and its biosynthesising enzyme, is highly abundant in leaves. These findings are of value to nutritional and the pharmaceutical industry.

}, keywords = {Diosgenin, Hypoglycemic Agents, Plant Extracts, Plants, Medicinal, Transcriptome, Trigonella}, issn = {2045-2322}, doi = {10.1038/s41598-022-17779-8}, author = {Naika, Mahantesha B N and Sathyanarayanan, Nitish and Sajeevan, Radha Sivarajan and Bhattacharyya, Teerna and Ghosh, Pritha and Iyer, Meenakshi S and Jarjapu, Mahita and Joshi, Adwait G and Harini, K and Shafi, K Mohamed and Kalmankar, Neha and Karpe, Snehal D and Mam, Bhavika and Pasha, Shaik Naseer and Sowdhamini, Ramanathan} } @article {118433, title = {Face neurons and super-normal stimuli:A window into visual processing.}, journal = {J Biosci}, volume = {47}, year = {2022}, month = {2022}, keywords = {Neurons, Pattern Recognition, Visual, Photic Stimulation, Visual Perception}, issn = {0973-7138}, author = {Bhalla, U S} } @article {106555, title = {Feeling like a {\textquoteright}real{\textquoteright} scientist.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 02 17}, abstract = {

Peer reviewing helped a graduate student to finally gain a sense of belonging within the research community.

}, issn = {2050-084X}, doi = {10.7554/eLife.77719}, author = {Varma, Aalok} } @article {108042, title = {Fine-scale spatial and temporal acoustic occurrence of island-associated odontocetes near a mid-oceanic atoll in the northern Indian Ocean}, journal = {MARINE ECOLOGY PROGRESS SERIES}, volume = {683}, year = {2022}, month = {02/2022}, pages = {195-208}, abstract = {

Temporal patterns of oceanic predators can provide valuable information on both lunar and diel influences not just on the distributions of these predators, but also on prey patches that are often difficult to study. Mid-oceanic island chains in the northern Indian Ocean have high odontocete occurrence, but the ecology of these animals is not well characterized. We investigated fine-scale spatial and temporal patterns of island-associated odontocetes using passive acoustic monitoring from January 2019 to January 2020 around Kavaratti Island, Lakshadweep, India. Based on opportunistic recordings in the presence of odontocetes, the majority of the detected whistles were likely made by spinner dolphins Stenella longirostris. We identified a resident population whose whistle occurrence was significantly influenced by month, site, and diel and lunar cycles. More acoustic detections were made in the northeast monsoon month of November and fewer during pre-monsoon and southwest monsoon periods. Distinct day-night differences along with fine-scale temporal variability were also observed, suggesting that delphinids use nearshore waters as a daytime resting habitat. Odontocete detections were highest during the new moon period and lowest during the first quarter phase. Detection rates were higher on the south side of the island. Our study shows that solar and lunar cycles modulate odontocete vocal occurrence, presumably through influences on their prey. Similarities of odontocete occurrence around Lakshadweep to other mid-oceanic island chains suggests that an island-associated micronekton community may exist around Lakshadweep that may also be important to other pelagic species targeted by local fisheries.

}, doi = {10.3354/meps13947}, author = {Panicker, Divya and Baumgartner, Mark F. and Stafford, Kathleen M.} } @article {107010, title = {Fine-tuned spatiotemporal dynamics of sporophylls in movement-assisted dichogamy: A study on Clerodendrum infortunatum}, journal = {PLANT SPECIES BIOLOGY }, year = {2022}, month = {02/2022}, abstract = {

Hermaphroditism is cost-effective because a common investment in reward and attractive structures yields benefits through both male and female reproductive success. However, the advantage is accompanied by an increased risk of self-pollen deposition, which is generally disadvantageous. Hermaphroditic plants reduce self-pollen deposition by separating sporophylls (a term applied to the stamens and carpels) either spatially (herkogamy) or temporally (dichogamy). In movement-assisted dichogamy, both sporophylls show coordinated motion in opposite directions. However, the effectiveness of this movement in reducing self-pollen deposition may be compromised at the point when the sporophylls cross each other and are close enough to interfere, resulting in a transition phase problem. The solution to this problem lies in the details of the spatiotemporal dynamics of the sporophylls in relation to their reproductive maturity. We studied these details across the floral lifetime of a protandrous shrub, Clerodendrum infortunatum (Lamiaceae), in rainforest fragments of the Western Ghats, India. We took photos of flowers at regular time intervals and measured sporophyll angles from the images. We also carried out a field experiment to determine stigma receptivity. We found that the stigma lobes remained narrowly opened at transition, and the stigma surfaces remained non-receptive. Our findings suggest that the effectiveness of dichogamy is maximized through two properties of the transition phase: physical resistance to self-pollen deposition by narrow stigma lobe opening and chemical non-receptivity of the stigma during this phase. This study emphasizes the importance of accessory adaptations in movement-assisted dichogamy to tackle the transition phase problem.

}, doi = {10.1111/1442-1984.12367}, author = {Mukhopadhyay, Amritendu and Quader, Suhel} } @article {109940, title = {First glimpse of enhancers in gene regulation.}, journal = {Nat Rev Genet}, year = {2022}, month = {2022 Apr 27}, issn = {1471-0064}, doi = {10.1038/s41576-022-00492-7}, author = {Notani, Dimple} } @inbook {111546, title = {Fluorescence Recovery After Photobleaching (FRAP) to Study Dynamics of the Structural Maintenance of Chromosome (SMC) Complex in Live Escherichia coli Bacteria.}, booktitle = {Methods Mol Biol}, volume = {2476}, year = {2022}, month = {2022}, pages = {31-41}, abstract = {

MukBEF, a structural maintenance of chromosome (SMC) complex, is an important molecular machine for chromosome organization and segregation in Escherichia coli. Fluorescently tagged MukBEF forms distinct spots (or "foci") composed of molecular assemblies in the cell, where it is thought to carry out most of its chromosome-associated activities. Here, we outline the technique of fluorescence recovery after photobleaching (FRAP) as a method to study the properties of YFP-tagged MukB in fluorescent foci. This method can provide important insight into the dynamics of MukB on DNA and be used to study its biochemical properties in vivo.

}, issn = {1940-6029}, doi = {10.1007/978-1-0716-2221-6_4}, author = {Badrinarayanan, Anjana and Leake, Mark C} } @article {108403, title = {FMRP protects the lung from xenobiotic stress by facilitating the Integrated Stress Response.}, journal = {J Cell Sci}, year = {2022}, month = {2022 Mar 23}, abstract = {

Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the Fragile X Mental Retardation Protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly. Analysis of airway stress responses in mice and in a murine cell line ex vivo, using the well-established Naphthalene (Nap) injury model, reveals that FMRP-deficient cells exhibit increased expression of markers of oxidative and genotoxic stress and increased cell death. Further inquiry shows that FMRP-deficient cells fail to actuate the Integrated Stress Response Pathway (ISR) and upregulate the transcription factor ATF4. Knockdown of ATF4 expression phenocopies the loss of FMRP. We extend our analysis of the role of FMRP to human bronchial BEAS-2B cells, using a 9, 10-Phenanthrenequinone air pollutant model, to find FMRP-deficient BEAS-2B also fail to actuate the ISR and exhibit greater susceptibility. Taken together, our data suggest that FMRP has a conserved role in protecting the airways by facilitating the ISR.

}, issn = {1477-9137}, doi = {10.1242/jcs.258652}, author = {Basu, Deblina Sain and Bhavsar, Rital and Gulami, Imtiyaz and Chavda, Saraswati and Lingamallu, Sai Manoz and Muddashetty, Ravi and Veeranna, Chandrakanth and Chattarji, Sumantra and Thimmulappa, Rajesh and Bhattacharya, Aditi and Guha, Arjun} } @article {113552, title = {Genome doubling enabled the expansion of yeast vesicle traffic pathways.}, journal = {Sci Rep}, volume = {12}, year = {2022}, month = {2022 Jul 02}, pages = {11213}, abstract = {

Vesicle budding and fusion in eukaryotes depend on a suite of protein types, such as Arfs, Rabs, coats and SNAREs. Distinct paralogs of these proteins act at distinct intracellular locations, suggesting a link between gene duplication and the expansion of vesicle traffic pathways. Genome doubling, a common source of paralogous genes in fungi, provides an ideal setting in which to explore this link. Here we trace the fates of paralog doublets derived from the 100-Ma-old hybridization event that gave rise to the whole genome duplication clade of budding yeast. We find that paralog doublets involved in specific vesicle traffic functions and pathways are convergently retained across the entire clade. Vesicle coats and adaptors involved in secretory and early-endocytic pathways are retained as doublets, at rates several-fold higher than expected by chance. Proteins involved in later endocytic steps and intra-Golgi traffic, including the entire set of multi-subunit and coiled-coil tethers, have reverted to singletons. These patterns demonstrate that selection has acted to expand and diversify the yeast vesicle traffic apparatus, across species and time.

}, keywords = {Blister, Gene Duplication, Golgi Apparatus, Saccharomyces cerevisiae, Saccharomycetales}, issn = {2045-2322}, doi = {10.1038/s41598-022-15419-9}, author = {Purkanti, Ramya and Thattai, Mukund} } @article {116716, title = {A genome-wide search of Toll/Interleukin-1 receptor (TIR) domain-containing adapter molecule (TICAM) and their evolutionary divergence from other TIR domain containing proteins.}, journal = {Biol Direct}, volume = {17}, year = {2022}, month = {2022 Sep 02}, pages = {24}, abstract = {

Toll/Interleukin-1 receptor (TIR) domains are cytoplasmic domain that mediates receptor signalling. These domains are present in proteins like Toll-like receptors (TLR), its signaling adaptors and Interleukins, that form a major part of the immune system. These TIR domain containing signaling adaptors binds to the TLRs and interacts with their TIR domains for downstream signaling. We have examined the evolutionary divergence across the tree of life of two of these TIR domain containing adaptor molecules (TICAM) i.e., TIR domain-containing adapter-inducing interferon-β (TRIF/TICAM1) and TIR domain containing adaptor molecule2 (TRAM/TICAM2), by using computational approaches. We studied their orthologs, domain architecture, conserved motifs, and amino acid variations. Our study also adds a timeframe to infer the duplication of TICAM protein from Leptocardii and later divergence into TICAM1/TRIF and TICAM2/TRAM. More evidence of TRIF proteins was seen, but the absence of conserved co-existing domains such as TRIF-NTD, TIR, and RHIM domains in distant relatives hints on diversification and adaptation to different biological functions. TRAM was lost in Actinopteri and has conserved domain architecture of TIR across species except in Aves. An additional isoform of TRAM, TAG (TRAM adaptor with the GOLD domain), could be identified in species in the Mesozoic era. Finally, the Hypothesis based Likelihood ratio test was applied to look for selection pressure amongst orthologues of TRIF and TRAM to search for positively selected sites. These residues were mostly seen in the non-structural region of the proteins. Overall, this study unravels evolutionary information on the adaptors TRAM and TRIF and how well they had duplicated to perform diverse functions by changes in their domain architecture across lineages.

}, keywords = {Adaptor Proteins, Vesicular Transport, Receptors, Interleukin-1, Signal Transduction, Toll-Like Receptors}, issn = {1745-6150}, doi = {10.1186/s13062-022-00335-9}, author = {Verma, Shailya and Sowdhamini, Ramanathan} } @article {108821, title = {Genome-wide SNP markers from fecal samples reveal anthropogenic impacts on connectivity: case of a small carnivore in the central Indian landscape}, journal = {ANIMAL CONSERVATION }, year = {2022}, month = {03/2022}, abstract = {

Maintaining gene flow among fragmented habitat patches is critical for the long-term persistence of wild species. Landscape genetics tools are often used to understand the impact of landscape features on gene flow among fragmented populations. The ability to detect the relationship between gene flow and landscape depends on the power of the genetic tools used, which increases with the number of genotyped loci. Next-generation sequencing (NGS) based methods allow genotyping of a high number of loci but are challenging to implement for non-invasive samples, which are commonly used in conservation genetics research. Here we assess the impact of landscape heterogeneity on jungle cat (Felis chaus) movement using genome-wide single nucleotide polymorphism (SNP) markers obtained from fecal samples, using a methylation-based DNA (MBD) enrichment method. We successfully genotyped 20 jungle cat individuals at 2246 SNP loci and compared our results to a previous study that used microsatellite markers and 93 individuals. Our results demonstrate the efficiency and robustness of the MBD enrichment approach with fecal samples in generating genome-wide data for endangered and cryptic species of conservation concern. Our landscape analyses revealed that roads and human-dominated land-use negatively impact jungle cat movement in central India. We explicitly quantified the uncertainty in our analyses and concluded that several thousand SNPs from fewer individuals provide more power than tens of microsatellites from more individuals, in quantifying the effects of landscape on gene flow. Our results provide insight into the impacts of anthropogenic habitat modification on an often-ignored small carnivore species. Insights on connectivity for such species can help policymakers and wildlife managers move beyond connectivity contingent on charismatic species to devise holistic landscape-level management plans for multiple carnivores.

}, doi = {10.1111/acv.12770}, author = {Tyagi, A. and Khan, A. and Thatte, P. and Ramakrishnan, U.} } @article {112960, title = {Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity.}, journal = {Int J Mol Sci}, volume = {23}, year = {2022}, month = {2022 Jun 20}, abstract = {

The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested-PD-1, PD-L1, PD-L2 and CTLA-4-remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

}, keywords = {Adenocarcinoma of Lung, Autophagy, B7-H1 Antigen, Genomics, Humans, Lung Neoplasms, Tumor Microenvironment, Water Pipe Smoking}, issn = {1422-0067}, doi = {10.3390/ijms23126848}, author = {Zaarour, Rania Faouzi and Sharda, Mohak and Azakir, Bilal and Hassan Venkatesh, Goutham and Abou Khouzam, Raefa and Rifath, Ayesha and Nizami, Zohra Nausheen and Abdullah, Fatima and Mohammad, Fatin and Karaali, Hajar and Nawafleh, Husam and Elsayed, Yehya and Chouaib, Salem} } @article {106553, title = {Global pleiotropic effects in adaptively evolved lacking CRP reveal molecular mechanisms that define the growth physiology.}, journal = {Open Biol}, volume = {12}, year = {2022}, month = {2022 Feb}, pages = {210206}, abstract = {

Evolution facilitates emergence of fitter phenotypes by efficient allocation of cellular resources in conjunction with beneficial mutations. However, system-wide pleiotropic effects that redress the perturbations to the apex node of the transcriptional regulatory networks remain unclear. Here, we elucidate that absence of global transcriptional regulator CRP in results in alterations in key metabolic pathways under glucose respiratory conditions, favouring stress- or hedging-related functions over growth-enhancing functions. Further, we disentangle the growth-mediated effects from the CRP regulation-specific effects on these metabolic pathways. We quantitatively illustrate that the loss of CRP perturbs proteome efficiency, as evident from metabolic as well as ribosomal proteome fractions, that corroborated with intracellular metabolite profiles. To address how copes with such systemic defect, we evolved mutant in the presence of glucose. Besides acquiring mutations in the promoter of glucose transporter , the evolved populations recovered the metabolic pathways to their pre-perturbed state coupled with metabolite re-adjustments, which altogether enabled increased growth. By contrast to mutant, the evolved strains remodelled their proteome efficiency towards biomass synthesis, albeit at the expense of carbon efficiency. Overall, we comprehensively illustrate the genetic and metabolic basis of pleiotropic effects, fundamental for understanding the growth physiology.

}, issn = {2046-2441}, doi = {10.1098/rsob.210206}, author = {Pal, Ankita and Iyer, Mahesh S and Srinivasan, Sumana and Narain Seshasayee, Aswin Sai and Venkatesh, K V} } @article {106556, title = {Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 Feb 17}, abstract = {

Many proteins that undergo sequential enzymatic modification in the Golgi cisternae are displayed at the plasma membrane as cell identity markers. The modified proteins, called glycans, represent a molecular code. The fidelity of this glycan code is measured by how accurately the glycan synthesis machinery realises the desired target glycan distribution for a particular cell type and niche. In this paper, we construct a simplified chemical synthesis model to quantitatively analyse the tradeoffs between the number of cisternae, and the number and specificity of enzymes, required to synthesize a prescribed target glycan distribution of a certain complexity to within a given fidelity. We find that to synthesize complex distributions, such as those observed in real cells, one needs to have multiple cisternae and precise enzyme partitioning in the Golgi. Additionally, for fixed number of enzymes and cisternae, there is an optimal level of specificity (promiscuity) of enzymes that achieves the target distribution with high fidelity. The geometry of the fidelity landscape in the multidimensional space of the number and specificity of enzymes, inter-cisternal transfer rates, and number of cisternae, provides a measure for robustness and identifies stiff and sloppy directions. Our results show how the complexity of the target glycan distribution and number of glycosylation enzymes places functional constraints on the Golgi cisternal number and enzyme specificity.

}, issn = {2050-084X}, doi = {10.7554/eLife.76757}, author = {Yadav, Alkesh and Vagne, Quentin and Sens, Pierre and Iyengar, Garud and Rao, Madan} } @article {116711, title = {Habitat use by mixed-species bird flocks in tropical forests of the Western Ghats, India}, journal = {JOURNAL OF TROPICAL ECOLOGY }, year = {2022}, month = {08/2022}, abstract = {

While mixed-species flocks of birds (hereafter {\textquoteright}flocks{\textquoteright}) have been widely studied, few studies have looked at the effect of habitat structure on flock presence and flocking propensity within a site. Here, we employ a use-availability approach in locations with flocks and random locations to ask whether habitat characteristics influence the presence of flocks, and whether structurally similar microhabitats support compositionally similar flocks. We also examine the effect of habitat on flock size and species richness, and the effect of intraspecifically gregarious flock participants on habitat selection. We find that flocks use a narrow subset of available tree density and canopy cover variation and prefer relatively less-dense areas with large trees and a complex foliage structure. Similar microhabitats do not result in compositionally similar flocks, and while foliage complexity was associated with flock size, no habitat characteristics influenced species richness. Flocks led by the intraspecifically gregarious western crowned warbler (Phylloscopus occipitalis), a potential nuclear species, showed preference for high foliage complexity and tree density. Thus, habitat preferences of intraspecifically gregarious species, which are followed by other species, could play a strong role in habitat selection in flocks. This suggests that degraded forests that cannot provide a suitable range of tree density, canopy cover, and/or complex vegetation structure may not support some core flock species around which flocks form, which may lead to decreased flocking in those patches.

}, doi = {10.1017/S026646742200030X}, author = {Hariharan, Priyanka and Bangal, Priti and Sridhar, Hari and Shanker, Kartik} } @article {108058, title = {Heterogeneity in Protein Folding and Unfolding Reactions.}, journal = {Chem Rev}, year = {2022}, month = {2022 Mar 11}, abstract = {

Proteins have dynamic structures that undergo chain motions on time scales spanning from picoseconds to seconds. Resolving the resultant conformational heterogeneity is essential for gaining accurate insight into fundamental mechanistic aspects of the protein folding reaction. The use of high-resolution structural probes, sensitive to population distributions, has begun to enable the resolution of site-specific conformational heterogeneity at different stages of the folding reaction. Different states populated during protein folding, including the unfolded state, collapsed intermediate states, and even the native state, are found to possess significant conformational heterogeneity. Heterogeneity in protein folding and unfolding reactions originates from the reduced cooperativity of various kinds of physicochemical interactions between various structural elements of a protein, and between a protein and solvent. Heterogeneity may arise because of functional or evolutionary constraints. Conformational substates within the unfolded state and the collapsed intermediates that exchange at rates slower than the subsequent folding steps give rise to heterogeneity on the protein folding pathways. Multiple folding pathways are likely to represent distinct sequences of structure formation. Insight into the nature of the energy barriers separating different conformational states populated during (un)folding can also be obtained by resolving heterogeneity.

}, issn = {1520-6890}, doi = {10.1021/acs.chemrev.1c00704}, author = {Bhatia, Sandhya and Udgaonkar, Jayant B} } @article {109306, title = {The hidden diversity and inland radiation of Sri Lanka{\textquoteright}s ground-dwelling geckos of the genus Cyrtodactylus (Reptilia: Gekkonidae)}, journal = {SYSTEMATICS AND BIODIVERSITY }, volume = {20}, year = {2022}, month = {04/2022}, pages = {1-25}, abstract = {

The genus Cyrtodactylus has recently been classified phylogenetically into several clades, subclades, groups, and some into Sri Lankan Cyrtodactylus. Certain complexes from the Indian subcontinent have been assigned to the "C. triedrus group". This group is comprised of medium-sized species (SVL 50.6-105.7mm) and are composed of five major species complexes: fraenatus, triedrus, deccanensis, jeyporensis, and collegalensis. Among these complexes, the latter four are composed of ground and litter dwelling species, which were previously assigned to the genus Geckoella; and is currently being treated as a subgenus. Cyrtodactylus triedrus, an endemic species of Sri Lanka, has long been considered a widely distributed single species in this part of the world. Based on morphological and phylogenetic evidences, we demonstrate that C. (G.) triedrus is not a single species, but a species complex. We also describe a new species that is restricted to intermediate savanna-mixed dry lowland forested habitats. Furthermore, we resurrect Geckoella pinciata, assign it to the genus Cyrtodactylus and designate a lectotype that we redescribe. The genetic divergence across species of the C. triedrus Glade varies between 11-26\% in the studied fragment of the mitochondrial NADH dehydrogenase subunit 2 gene. The molecular phylogeny of the ground dwelling radiation of the subgenus Geckoella indicates deep splits between the Indian species and Sri Lankan endemic C. (G.) triedrus sensu stricto, and between Indian dry and wet zone clades. Cyrtodactylus (G.). triedrus is restricted to the moist or submontane forests in the Central highlands of Sri Lanka and is redescribed herein based on its holotype.

}, doi = {10.1080/14772000.2022.2039319}, author = {Amarasinghe, AAT and Karunarathna, Suranjan and Campbell, Patrick D. and Gayan, AKA and Ranasinghe, WDB and De Silva, Anslem and Mirza, Zeeshan A.} } @article {109678, title = {How methodological changes have influenced our understanding of population structure in threatened species: insights from tiger populations across India.}, journal = {Philos Trans R Soc Lond B Biol Sci}, volume = {377}, year = {2022}, month = {2022 Jun 06}, pages = {20200418}, abstract = {

Unprecedented advances in sequencing technology in the past decade allow a better understanding of genetic variation and its partitioning in natural populations. Such inference is critical to conservation: to understand species biology and identify isolated populations. We review empirical population genetics studies of Endangered Bengal tigers within India, where 60-70\% of wild tigers live. We assess how changes in marker type and sampling strategy have impacted inferences by reviewing past studies, and presenting three novel analyses including a single-nucleotide polymorphism (SNP) panel, genome-wide SNP markers, and a whole-mitochondrial genome network. At a broad spatial scale, less than 100 SNPs revealed the same patterns of population clustering as whole genomes (with the exception of one additional population sampled only in the SNP panel). Mitochondrial DNA indicates a strong structure between the northeast and other regions. Two studies with more populations sampled revealed further substructure within Central India. Overall, the comparison of studies with varied marker types and sample sets allows more rigorous inference of population structure. Yet sampling of some populations is limited across all studies, and these should be the focus of future sampling efforts. We discuss challenges in our understanding of population structure, and how to further address relevant questions in conservation genetics. This article is part of the theme issue {\textquoteright}Celebrating 50 years since Lewontin{\textquoteright}s apportionment of human diversity{\textquoteright}.

}, keywords = {Animals, Conservation of Natural Resources, Endangered Species, Genetic Variation, Genetics, Population, India, Prospective Studies, Tigers}, issn = {1471-2970}, doi = {10.1098/rstb.2020.0418}, author = {Aylward, Megan and Sagar, Vinay and Natesh, Meghana and Ramakrishnan, Uma} } @article {104897, title = {HT-SELEX-based identification of binding pre-miRNA hairpin-motif for small molecules.}, journal = {Mol Ther Nucleic Acids}, volume = {27}, year = {2022}, month = {2022 Mar 08}, pages = {165-174}, abstract = {

Selective targeting of biologically relevant RNAs with small molecules is a long-standing challenge due to the lack of clear understanding of the binding RNA motifs for small molecules. The standard SELEX procedure allows the identification of specific RNA binders (aptamers) for the target of interest. However, more effort is needed to identify and characterize the sequence-structure motifs in the aptamers important for binding to the target. Herein, we described a strategy integrating high-throughput (HT) sequencing with conventional SELEX followed by bioinformatic analysis to identify aptamers with high binding affinity and target specificity to unravel the sequence-structure motifs of pre-miRNA, which is essential for binding to the recently developed new water-soluble small-molecule CMBL3aL. To confirm the fidelity of this approach, we investigated the binding of CMBL3aL to the identified motifs by surface plasmon resonance (SPR) spectroscopy and its potential regulatory activity on dicer-mediated cleavage of the obtained aptamers and endogenous pre-miRNAs comprising the identified motif in its hairpin loop. This new approach would significantly accelerate the identification process of binding sequence-structure motifs of pre-miRNA for the compound of interest and would contribute to increase the spectrum of biomedical application.

}, issn = {2162-2531}, doi = {10.1016/j.omtn.2021.11.021}, author = {Mukherjee, Sanjukta and Murata, Asako and Ishida, Ryoga and Sugai, Ayako and Dohno, Chikara and Hamada, Michiaki and Krishna, Sudhir and Nakatani, Kazuhiko} } @article {105480, title = {A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome.}, journal = {Biol Open}, year = {2022}, month = {2022 Jan 13}, abstract = {

Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a "disease-in-a-dish" model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.

}, issn = {2046-6390}, doi = {10.1242/bio.059066}, author = {Akhtar, Bilal M and Bhatia, Priyanka and Acharya, Shubhra and Sharma, Sanjeev and Sharma, Yojet and Aswathy, B S and Ganapathy, Kavina and Vasudevan, Anil and Raghu, Padinjat} } @article {131931, title = {Human{\textendash}elephant conflict mitigation as a public good: what determines fence maintenance?}, journal = {Ecology and Society}, volume = {27}, year = {2022}, month = {2022}, abstract = {

Negative interactions between humans and elephants are known to have serious consequences, resulting in loss of life and deterioration in the quality of life for both species. Reducing human{\textendash}elephant conflicts (HEC) is essential for elephant conservation as well as social justice. Non-lethal electric fences placed around villages or communities are a widely used intervention to mitigate HEC. Such barriers act as non-excludable and non-subtractable resources{\textemdash}i.e., public goods{\textemdash}that must be maintained collectively by beneficiaries or the State. Despite being fairly effective when well maintained, most such fences in northeast India are poorly maintained. This leads to our central question: why are some fences well maintained and others poorly maintained? We studied 19 such fences using qualitative comparative analysis, Ostrom{\textquoteright}s social-ecological systems framework, and a grounded theory approach, incorporating qualitative social science tools. We found that, contrary to our hypothesis, the functionality of fences cannot be predicted based on the design of the fence, whether or not the community made cash payments, or ethnic homogeneity or leadership in the village. Instead, we found there are three potential pathways of maintenance: (1) a community maintainer, (2) the community self-organizes, and (3) the Forest Department. Maintenance occurs when there is a congruence between perceived costs and benefits for the entity responsible for fence maintenance. These costs and benefits are diverse, including not just material benefits but intangibles like goodwill, sense of safety, social standing, and a feeling of fairness. We highlight these factors and provide recommendations for practitioners and policy.

}, doi = {10.5751/ES-13271-270324}, author = {Kamdar, Arjun and Baishya, Hiten Kumar and Nagendra, Harini and Ratnam, Jayashree and Smith, David and Sekar, Nitin} } @article {117966, title = {Identification of potential modulators of IFITM3 by in-silico modeling and virtual screening.}, journal = {Sci Rep}, volume = {12}, year = {2022}, month = {2022 Sep 24}, pages = {15952}, abstract = {

IFITM3 is a transmembrane protein that confers innate immunity. It has been established to restrict entry of multiple viruses. Overexpression of IFITM3 has been shown to be associated with multiple cancers, implying IFITM3 to be good therapeutic target. The regulation of IFITM3 activity is mediated by multiple post-translational modifications (PTM). In this study, we have modelled the structure of IFITM3, consistent with experimental predictions on its membrane topology. MD simulation in membrane-aqueous environment revealed the stability of the model. Ligand binding sites on the IFITM3 surface were predicted and it was observed that the best site includes important residues involved in PTM and has good druggable score. Molecular docking was performed using FDA approved ligands and natural ligands from Super Natural II database. The ligands were re-ranked by calculating binding free energy. Select docking complexes were simulated again to substantiate the binding between ligand and IFITM3. We observed that known drugs like Eluxadoline and natural products like SN00224572 and Parishin A have good binding affinity against IFITM3. These ligands form persistent interactions with key lysine residues (Lys83, Lys104) and hence can potentially alter the activity of IFITM3. The results of this computational study can provide a starting point for experimental investigations on IFITM3 modulators.

}, keywords = {Biological Products, Ligands, Lysine, Molecular Docking Simulation, RNA-Binding Proteins}, issn = {2045-2322}, doi = {10.1038/s41598-022-20259-8}, author = {Tiwari, Vikas and Viswanath, Shruthi} } @article {115033, title = {Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3 -/y rat model of autism}, journal = {Mol Autism.}, volume = {13}, year = {2022}, month = {07/2022}, pages = {34}, abstract = {

Background: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3.

Methods: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3-/y rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3-/y rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM).

Results: We observed that, unlike the wildtype, Nlgn3-/y rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3-/y rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3-/y than wildtype rats, indicating the functional impact of the increased cellular excitability.

Limitations: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life.

Conclusions: We describe altered fear responses in Nlgn3-/y rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD.

}, doi = {10.1186/s13229-022-00511-8}, author = {Anstey, NJ and Kapgal, V. and Tiwari, S. and Watson, TC and Toft, AKH and Dando, OR and Inkpen, FH and Baxter, PS and Kozi{\'c}, Z and Jackson, AD and He, X and Nawaz, MS and Kayenaat, A and Bhattacharya, A and Wyllie, DJA and Chattarji, Sumantra and Wood, ER and Hardt, O and Kind, PC} } @article {105164, title = {Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences.}, journal = {Mol Ther}, year = {2022}, month = {2022 Jan 06}, abstract = {

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a DENV-2 NS1 protein coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. Vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying of intracellular IFN-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios and immune gene profiling suggest a strong Th1-dominant immune response. Finally, passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design; offering a novel vaccine candidate with a possible broad spectrum protection and successful clinical translation either as a stand-alone or in a mix and match strategy.

}, issn = {1525-0024}, doi = {10.1016/j.ymthe.2022.01.013}, author = {Sankaradoss, Arun and Jagtap, Suraj and Nazir, Junaid and Moula, Shefta-E and Modak, Ayan and Fialho, Joshuah and Iyer, Meenakshi and Shastri, Jayanthi S and Dias, Mary and Gadepalli, Ravisekhar and Aggarwal, Alisha and Vedpathak, Manoj and Agrawal, Sachee and Pandit, Awadhesh and Nisheetha, Amul and Kumar, Anuj and Bordoloi, Mahasweta and Shafi, Mohamed and Shelar, Bhagyashree and Balachandra, Swathi S and Damodar, Tina and Masika, Moses Muia and Mwaura, Patrick and Anzala, Omu and Muthumani, Kar and Sowdhamini, Ramanathan and Medigeshi, Guruprasad R and Roy, Rahul and Pattabiraman, Chitra and Krishna, Sudhir and Sreekumar, Easwaran} } @article {115019, title = {Impact of Phyllosphere Methylobacterium on Host Rice Landraces}, journal = {MICROBIOLOGY SPECTRUM}, year = {2022}, month = {07/2022}, abstract = {

Plants are associated with diverse microbes in nature. Do the microbes increase host plant health, and can they be used for agricultural applications? This is an important question that must be answered in the field rather than in the laboratory or greenhouse.

The genus Methylobacterium includes widespread plant-associated bacteria that are abundant in the plant phyllosphere (leaf surfaces), consume plant-secreted methanol, and can produce plant growth-promoting metabolites. However, despite the potential to increase agricultural productivity, their impact on host fitness in the natural environment is relatively poorly understood. Here, we conducted field experiments with three traditionally cultivated rice landraces from northeastern India. We inoculated seedlings with native versus nonnative phyllosphere Methylobacterium strains and found significant impacts on plant growth and grain yield. However, these effects were variable. Whereas some Methylobacterium isolates were beneficial for their host, others had no impact or were no more beneficial than the bacterial growth medium on its own. Host plant benefits were not consistently associated with Methylobacterium colonization and did not have altered phyllosphere microbiome composition, changes in the early expression of plant stress response pathways, or bacterial auxin production. We provide the first demonstration of the benefits of phyllosphere Methylobacterium for rice yield under field conditions and highlight the need for further analysis to understand the mechanisms underlying these benefits. Given that the host landrace-Methylobacterium relationship was not generalizable, future agricultural applications will require careful testing to identify coevolved host-bacterium pairs that may enhance the productivity of high-value rice varieties. IMPORTANCE Plants are associated with diverse microbes in nature. Do the microbes increase host plant health, and can they be used for agricultural applications? This is an important question that must be answered in the field rather than in the laboratory or greenhouse. We tested the effects of native, leaf-inhabiting bacteria (genus Methylobacterium) on traditionally cultivated rice varieties in a crop field. We found that inoculation with some bacteria increased rice grain production substantially while a nonnative bacterium reduced plant health. Overall, the effect of bacterial inoculation varied across pairs of rice varieties and their native bacteria. Thus, knowledge of evolved associations between specific bacteria hosted by specific rice varieties is necessary to develop ways to increase the yield of traditional rice landraces and preserve these important sources of cultural and genetic diversity.

}, doi = {10.1128/spectrum.00810-22}, author = {Sanjenbam, Pratibha and Shivaprasad, P. V and Agashe, Deepa} } @article {157118, title = {Impact of Phyllosphere on Host Rice Landraces.}, journal = {Microbiol Spectr}, volume = {10}, year = {2022}, month = {2022 Aug 31}, pages = {e0081022}, abstract = {

The genus includes widespread plant-associated bacteria that are abundant in the plant phyllosphere (leaf surfaces), consume plant-secreted methanol, and can produce plant growth-promoting metabolites. However, despite the potential to increase agricultural productivity, their impact on host fitness in the natural environment is relatively poorly understood. Here, we conducted field experiments with three traditionally cultivated rice landraces from northeastern India. We inoculated seedlings with native versus nonnative phyllosphere strains and found significant impacts on plant growth and grain yield. However, these effects were variable. Whereas some isolates were beneficial for their host, others had no impact or were no more beneficial than the bacterial growth medium on its own. Host plant benefits were not consistently associated with colonization and did not have altered phyllosphere microbiome composition, changes in the early expression of plant stress response pathways, or bacterial auxin production. We provide the first demonstration of the benefits of phyllosphere for rice yield under field conditions and highlight the need for further analysis to understand the mechanisms underlying these benefits. Given that the host landrace- relationship was not generalizable, future agricultural applications will require careful testing to identify coevolved host-bacterium pairs that may enhance the productivity of high-value rice varieties. Plants are associated with diverse microbes in nature. Do the microbes increase host plant health, and can they be used for agricultural applications? This is an important question that must be answered in the field rather than in the laboratory or greenhouse. We tested the effects of native, leaf-inhabiting bacteria (genus ) on traditionally cultivated rice varieties in a crop field. We found that inoculation with some bacteria increased rice grain production substantially while a nonnative bacterium reduced plant health. Overall, the effect of bacterial inoculation varied across pairs of rice varieties and their native bacteria. Thus, knowledge of evolved associations between specific bacteria hosted by specific rice varieties is necessary to develop ways to increase the yield of traditional rice landraces and preserve these important sources of cultural and genetic diversity.

}, keywords = {epiphytes; grain yield; host fitness; host-bacterial interaction; phyllosphere; rice landraces.}, issn = {2165-0497}, doi = {10.1128/spectrum.00810-22}, author = {Sanjenbam, Pratibha and Shivaprasad, P V and Agashe, Deepa} } @article {113534, title = {In Ovo and Ex Ovo Methods to Study Avian Inner Ear Development.}, journal = {J Vis Exp}, year = {2022}, month = {2022 Jun 16}, abstract = {

The inner ear perceives sound and maintains balance using the cochlea and vestibule. It does this by using a dedicated mechanosensory cell type known as the hair cell. Basic research in the inner ear has led to a deep understanding of how the hair cell functions, and how dysregulation can lead to hearing loss and vertigo. For this research, the mouse has been the pre-eminent model system. However, mice, like all mammals, have lost the ability to replace hair cells. Thus, when trying to understand cellular therapies for restoring inner ear function, complementary studies in other vertebrate species could provide further insights. The auditory epithelium of birds, the basilar papilla (BP), is a sheet of epithelium composed of mechanosensory hair cells (HCs) intercalated by supporting cells (SCs). Although the anatomical architecture of the basilar papilla and the mammalian cochlea differ, the molecular mechanisms of inner ear development and hearing are similar. This makes the basilar papilla a useful system for not only comparative studies but also to understand regeneration. Here, we describe dissection and manipulation techniques for the chicken inner ear. The technique shows genetic and small molecule inhibition methods, which offer a potent tool for studying the molecular mechanisms of inner ear development. In this paper, we discuss in ovo electroporation techniques to genetically perturb the basilar papilla using CRIPSR-Cas9 deletions, followed by dissection of the basilar papilla. We also demonstrate the BP organ culture and optimal use of culture matrices, to observe the development of the epithelium and the hair cells.

}, keywords = {Animals, Chickens, Cochlea, Hair Cells, Auditory, Mammals, Mice, Organ of Corti, Vestibule, Labyrinth}, issn = {1940-087X}, doi = {10.3791/64172}, author = {Singh, Nishant and Prakash, Anubhav and Chakravarthy, Suraj Ranganath and Kaushik, Raman and Ladher, Raj K} } @article {115044, title = {Increased complexity of worker CHC profiles in Apis dorsata correlates with nesting ecology.}, journal = {PLoS One}, volume = {17}, year = {2022}, month = {2022}, pages = {e0271745}, abstract = {

Cuticular hydrocarbons (CHC) are known to serve as discrimination cues and will trigger defence behaviour in a plethora of eusocial insects. However, little is known how about nestmate recognition ability selects for CHC diversification. In this study we investigate differences in CHC composition of four major honey bee species with respect to the differences in their nesting behavior. In contrast to A. mellifera, A. cerana and A. florea, the giant honey bee A. dorsata prefers to build their nests in aggregations with very small spatial distances between nests, which increases the probability of intrusions. Thus, A. dorsata exhibits a particularly challenging nesting behavior which we hypothesize should be accompanied with an improved nestmate recognition system. Comparative analyses of the worker CHC profiles indicate that A. dorsata workers exhibit a unique and more complex CHC profile than the other three honey bee species. This increased complexity is likely based on a developmental process that retains the capability to synthesize methyl-branched hydrocarbons as adults. Furthermore, two sets of behavioral experiments provide evidence that A. dorsata shows an improved nestmate discrimination ability compared to the phylogenetically ancestral A. florea, which is also open-nesting but does not form nest aggregations. The results of our study suggest that ecological traits like nesting in aggregation might be able to drive CHC profile diversification even in closely related insect species.

}, keywords = {Animals, Bees, Cues, Hydrocarbons, Nesting Behavior}, issn = {1932-6203}, doi = {10.1371/journal.pone.0271745}, author = {Maihoff, Fabienne and Bohlke, Kyte and Brockmann, Axel and Schmitt, Thomas} } @article {113539, title = {An inducible potato (E,E)-farnesol synthase confers tolerance against bacterial pathogens in potato and tobacco.}, journal = {Plant J}, year = {2022}, month = {2022 Jul 02}, abstract = {

Terpene synthases (TPSs) have diverse biological functions in plants. Though the roles of TPSs in herbivore defense are well established in many plant species, their role in bacterial defense has been scarce and is emerging. Through functional genomics, here we report the in planta role of potato (Solanum tuberosum) terpene synthase (StTPS18) in bacterial defense. Expression of StTPS18 was highest in leaves and was induced in response to Pseudomonas syringae and methyl jasmonate treatments. The recombinant StTPS18 exhibited bona fide (E,E)-farnesol synthase activity forming a sesquiterpenoid, (E,E)-farnesol as the sole product, utilising (E,E)-farnesyl diphosphate (FPP). Subcellular localization of GFP fusion protein revealed that StTPS18 is localized to the cytosol. Silencing and overexpression of StTPS18 in potato resulted in reduced and enhanced tolerance, respectively, to bacterial pathogens P. syringae and Ralstonia solanacearum. Bacterial growth assay using medium containing (E,E)-farnesol significantly inhibited P. syringae growth. Moreover, StTPS18 overexpressing transgenic potato and Nicotiana tabacum leaves, and (E,E)-farnesol and P. syringae infiltrated potato leaves exhibited elevated expression of sterol pathway and members of pathogenesis-related genes with enhanced phytosterol accumulation. Interestingly, enhanced phytosterols in C -(E,E)-farnesol infiltrated potato leaves were devoid of any noticeable C labeling, indicating no direct utilization of (E,E)-farnesol in phytosterols formation. Furthermore, leaves of StTPS18 overexpressing transgenic lines had no detectable (E,E)-farnesol similar to the control plant, and emitted lower levels of sesquiterpenes than the control. These findings point towards an indirect involvement of StTPS18 and its product (E,E)-farnesol in bacterial defense through upregulation of phytosterol biosynthesis and defense genes.

}, issn = {1365-313X}, doi = {10.1111/tpj.15890}, author = {Dwivedi, Varun and Kumar, Sarma Rajeev and Shilpashree, H B and Krishna, Ram and Rao, Srinivas and Shasany, Ajit K and Olsson, Shannon B and Nagegowda, Dinesh A} } @article {117962, title = {Initiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.}, journal = {PLoS Biol}, volume = {20}, year = {2022}, month = {2022 Sep}, pages = {e3001777}, abstract = {

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the down-regulation of caspase-8 as a biomarker of a cell entering the wound healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be down-regulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.

}, keywords = {Biomarkers, Caspase 8, Cues, Epigenesis, Genetic, Wound Healing}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3001777}, author = {Bhatt, Tanay and Dey, Rakesh and Hegde, Akshay and Ketkar, Alhad Ashok and Pulianmackal, Ajai J and Deb, Ashim P and Rampalli, Shravanti and Jamora, Colin} } @article {115258, title = {Insights from the analysis of draft genome sequence of Crocus sativus L}, journal = {Bioinformation}, volume = {18}, year = {2022}, month = {01/2022}, pages = {1-13}, abstract = {

Saffron (Crocus sativus L.) is the low yielding plant of medicinal and economic importance. Therefore, it is of interest to report the draft genome sequence of C. sativus. The draft genome of C. sativus has been assembled using Illumina sequencing and is 3.01 Gb long covering 84.24\% of genome. C. sativus genome annotation identified 53,546 functional genes (including 5726 transcription factors), 862,275 repeats and 964,231 SSR markers. The genes involved in the apocarotenoids biosynthesis pathway (crocin, crocetin, picrocrocin, and safranal) were found in the draft genome analysis.

}, doi = {10.6026/97320630018001}, author = {Ambardar, S. and Vakhlu, Jyoti and Sowdhamini, R.} } @article {112956, title = {Integration of visual and antennal mechanosensory feedback during head stabilization in hawkmoths.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 Jun 27}, abstract = {

During flight maneuvers, insects exhibit compensatory head movements which are essential for stabilizing the visual field on their retina, reducing motion blur, and supporting visual self-motion estimation. In Diptera, such head movements are mediated visual feedback from their compound eyes that detect retinal slip, as well as rapid mechanosensory feedback from their halteres - the modified hindwings that sense the angular rates of body rotations. Because non-Dipteran insects lack halteres, it is not known if mechanosensory feedback about body rotations plays any role in their head stabilization response. Diverse non-Dipteran insects are known to rely on visual and antennal mechanosensory feedback for flight control. In hawkmoths, for instance, reduction of antennal mechanosensory feedback severely compromises their ability to control flight. Similarly, when the head movements of freely-flying moths are restricted, their flight ability is also severely impaired. The role of compensatory head movements as well as multimodal feedback in insect flight raises an interesting question: in insects that lack halteres, what sensory cues are required for head stabilization? Here, we show that in the nocturnal hawkmoth , compensatory head movements are mediated by combined visual and antennal mechanosensory feedback. We subjected tethered moths to open-loop body roll rotations under different lighting conditions, and measured their ability to maintain head angle in the presence or absence of antennal mechanosensory feedback. Our study suggests that head stabilization in moths is mediated primarily by visual feedback during roll movements at lower frequencies, whereas antennal mechanosensory feedback is required when roll occurs at higher frequency. These findings are consistent with the hypothesis that control of head angle results from a multimodal feedback loop that integrates both visual and antennal mechanosensory feedback, at different latencies. At adequate light levels, visual feedback is sufficient for head stabilization primarily at low frequencies of body roll. However, under dark conditions, antennal mechanosensory feedback is essential for the control of head movements at high of body roll.

}, issn = {2050-084X}, doi = {10.7554/eLife.78410}, author = {Chatterjee, Payel and Prusty, Agnish Dev and Mohan, Umesh and Sane, Sanjay P} } @article {120168, title = {Integrative network analysis interweaves the missing links in cardiomyopathy diseasome.}, journal = {Sci Rep}, volume = {12}, year = {2022}, month = {2022 Nov 16}, pages = {19670}, abstract = {

Cardiomyopathies are progressive disease conditions that give rise to an abnormal heart phenotype and are a leading cause of heart failures in the general population. These are complex diseases that show co-morbidity with other diseases. The molecular interaction network in the localised disease neighbourhood is an important step toward deciphering molecular mechanisms underlying these complex conditions. In this pursuit, we employed network medicine techniques to systematically investigate cardiomyopathy{\textquoteright}s genetic interplay with other diseases and uncover the molecular players underlying these associations. We predicted a set of candidate genes in cardiomyopathy by exploring the DIAMOnD algorithm on the human interactome. We next revealed how these candidate genes form association across different diseases and highlighted the predominant association with brain, cancer and metabolic diseases. Through integrative systems analysis of molecular pathways, heart-specific mouse knockout data and disease tissue-specific transcriptomic data, we screened and ascertained prominent candidates that show abnormal heart phenotype, including NOS3, MMP2 and SIRT1. Our computational analysis broadens the understanding of the genetic associations of cardiomyopathies with other diseases and holds great potential in cardiomyopathy research.

}, keywords = {Algorithms, Animals, Cardiomyopathies, Heart, Humans, Mice, Phenotype}, issn = {2045-2322}, doi = {10.1038/s41598-022-24246-x}, author = {Chauhan, Pankaj Kumar and Sowdhamini, Ramanathan} } @article {108057, title = {Interaction of human erythrocyte catalase with air-water interface in cryoEM.}, journal = {Microscopy (Oxf)}, volume = {71}, year = {2022}, month = {02/2022}, pages = {i51-i59}, abstract = {

One of the key goals in single-particle cryo-microscopy is to obtain a uniform distribution of particle orientations, so that the three-dimensional structure has isotropic resolution in Fourier space. A common problem arises from the interaction of protein molecules with the air-water interface that exists on both surfaces of the thin film of liquid that is formed prior to plunge-freezing into liquid ethane. Some proteins and other macromolecular complexes are disrupted by interaction with the air-water interface. Other proteins or macromolecules either become concentrated through their interaction with the interface or are excluded because they bind strongly to some other part of the grid or the filter paper used in blotting. In this paper, the interaction of human erythrocyte catalase with the air-water interface is investigated and minimized by the addition of certain detergents. Detergents can form an amphipathic monolayer at the air-water interface that creates a barrier and leaves the molecules free to adopt a variety of orientations, thus facilitating the 3D structure determination. These results suggest that further characterization and development of detergents for cryo-microscopy plunge-freezing would be useful.

}, doi = {10.1093/jmicro/dfab037 }, author = {Chen, S. and Li, J. and Vinothkumar, Kutti R and Henderson, R.} } @article {113535, title = {Investigation of Transposon DNA Methylation and Copy Number Variation in Plants Using Southern Hybridisation.}, journal = {Bio Protoc}, volume = {12}, year = {2022}, month = {2022 Jun 05}, pages = {e4432}, abstract = {

Plant genomes are pronouncedly enriched in repeat elements such as transposons. These repeats are epigenetically regulated by DNA methylation. Whole genome high-depth sequencing after bisulfite treatment remains an expensive and laborious method to reliably profile the DNA methylome, especially when considering large genomes such as in crops. Here, we present a simple reproducible Southern hybridisation-based assay to obtain incontrovertible methylation patterns from targeted regions in the rice genome. By employing minor but key modifications, we reliably detected transposon copy number variations over multiple generations. This method can be regarded as a gold standard for validation of epigenetic variations at target loci, and the consequent proliferation of transposons, or segregation in several plant replicates and genotypes. .

}, issn = {2331-8325}, doi = {10.21769/BioProtoc.4432}, author = {Vivek Hari Sundar G and Shivaprasad, P V} } @article {120165, title = {Irregular particle morphology and membrane rupture facilitate ion gradients in the lumen of phagosomes.}, journal = {Biophys Rep (N Y)}, volume = {2}, year = {2022}, month = {2022 Sep 14}, pages = {100069}, abstract = {

Localized fluxes, production, and/or degradation coupled to limited diffusion are well known to result in stable spatial concentration gradients of biomolecules in the cell. In this study, we demonstrate that this also holds true for small ions, since we found that the close membrane apposition between the membrane of a phagosome and the surface of the cargo particle it encloses, together with localized membrane rupture, suffice for stable gradients of protons and iron cations within the lumen of the phagosome. Our data show that, in phagosomes containing hexapod-shaped silica colloid particles, the phagosomal membrane is ruptured at the positions of the tips of the rods, but not at other positions. This results in the confined leakage at these positions of protons and iron from the lumen of the phagosome into the cytosol. In contrast, acidification and iron accumulation still occur at the positions of the phagosomes nearer to the cores of the particles. Our study strengthens the concept that coupling metabolic and signaling reaction cascades can be spatially confined by localized limited diffusion.

}, issn = {2667-0747}, doi = {10.1016/j.bpr.2022.100069}, author = {Baranov, Maksim V and Ioannidis, Melina and Balahsioui, Sami and Boersma, Auke and de Boer, Rinse and Kumar, Manoj and Niwa, Masato and Hirayama, Tasuku and Zhou, Qintian and Hopkins, Terrence M and Grijpstra, Pieter and Thutupalli, Shashi and Sacanna, Stefano and van den Bogaart, Geert} } @article {108049, title = {LIM domain-wide comprehensive virtual mutagenesis provides structural rationale for cardiomyopathy mutations in CSRP3.}, journal = {Sci Rep}, volume = {12}, year = {2022}, month = {2022 Mar 03}, pages = {3562}, abstract = {

Cardiomyopathies are a severe and chronic cardiovascular burden worldwide, affecting a large cohort in the general population. Cysteine and glycine-rich protein 3 (CSRP3) is one of key proteins implicated in dominant dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). In this study, we device a rapid in silico screening protocol that creates a mutational landscape map for all possible allowed and disallowed substitutions in the protein of interest. This map provides the structural and functional insights on the stability of LIM domains of CSRP3. Further, the sequence analysis delineates the eukaryotic CSRP3 protein orthologs which complements the mutational map, but provide limited information of amino acid exchanges. Next, we also evaluated the effect of HCM/DCM mutations on these domains. One of highly destabilising mutations-L44P (also disease causing) and a neutral mutation-L44M were further subjected to molecular dynamics (MD) simulations. The results establish that L44P substitution affects the LIM domain structure by altering secondary structure and due to loss of hydrophobic interaction with Phenylananine 35. The present study provides a useful perspective to our understanding of the role of mutations in the CSRP3 LIM domains and their evolution. This study provides a novel computational screening method for quick identification of key mutation sites for specific protein structures that can reduce the burden on experimental research.

}, issn = {2045-2322}, doi = {10.1038/s41598-022-07553-1}, author = {Chauhan, Pankaj Kumar and Sowdhamini, Ramanathan} } @article {110624, title = {Local translation provides the asymmetric distribution of CaMKII required for associative memory formation.}, journal = {Curr Biol}, year = {2022}, month = {2022 May 04}, abstract = {

How compartment-specific local proteomes are generated and maintained is inadequately understood, particularly in neurons, which display extreme asymmetries. Here we show that local enrichment of Ca/calmodulin-dependent protein kinase II (CaMKII) in axons of Drosophila mushroom body neurons is necessary for cellular plasticity and associative memory formation. Enrichment is achieved via enhanced axoplasmic translation of CaMKII mRNA, through a mechanism requiring the RNA-binding protein Mub and a 23-base Mub-recognition element in the CaMKII 3{\textquoteright} UTR. Perturbation of either dramatically reduces axonal, but not somatic, CaMKII protein without altering the distribution or amount of mRNA in\ vivo, and both are necessary and sufficient to enhance axonal translation of reporter mRNA. Together, these data identify elevated levels of translation of an evenly distributed mRNA as a novel strategy for generating subcellular biochemical asymmetries. They further demonstrate the importance of distributional asymmetry in the computational and biological functions of neurons.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2022.04.047}, author = {Chen, Nannan and Zhang, Yunpeng and Adel, Mohamed and Kuklin, Elena A and Reed, Martha L and Mardovin, Jacob D and Bakthavachalu, Baskar and VijayRaghavan, K and Ramaswami, Mani and Griffith, Leslie C} } @article {116185, title = {Mapping the distribution and extent of India{\textquoteright}s semi-arid open natural ecosystems}, journal = {JOURNAL OF BIOGEOGRAPHY}, year = {2022}, month = {08/2022}, abstract = {

Aim Non-forested open natural ecosystems (ONEs) support high biodiversity as well as livelihoods of millions of pastoralists, but are highly threatened due to land conversion. To improve the recognition of their value, we generated a high-resolution (30 m) map of ONEs in the low elevation arid and semi-arid regions of India. Location Indian subcontinent. Taxon Open natural ecosystems, consisting of a range of non-forested habitats. Methods We used public datasets in the Google Earth Engine catalogue to identify and mask out pixels with non-ONE land-cover types, and biophysical attributes outside the environmental envelopes of ONEs. We used 181,812 ONE and 116,447 non-ONE training points along with the input composite image to train random forest classifiers to estimate the probability of a pixel being an ONE. We developed a series of local classifiers for each of eight regions of interest and created a mask of pixels with \>= 50\% probability of being an ONE. Results The overall classification accuracy for this map was 85\%, with a Kappa statistic of 0.70. We find that ONEs cover approximately 320,000 km(2) (10\%) of India{\textquoteright}s land surface, but \<5\% of ONEs are covered under the existing protected area network of India. ONE areas vary greatly by region, from 6 km(2) in New Delhi (0.4\% area) to 115,069 km(2) in Rajasthan (33\% area). Main Conclusions A large proportion of India{\textquoteright}s geographical area represents an ecosystem that is un-recognized and under-protected. This open data source can be used by policy makers and planners to exclude these habitats when considering the location of renewable energy, tree planting for carbon sequestration and other development projects that negatively impact ONEs. We encourage further refinement of ONE maps in India, incorporating vegetation and floristic characteristics, as well as further consideration of these vulnerable neglected ecosystems in other regions of the world.

}, doi = {10.1111/jbi.14471}, author = {Madhusudan, M. D. and Vanak, Abi Tamim} } @article {121911, title = {Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.}, journal = {RSC Med Chem}, volume = {13}, year = {2022}, month = {2022 Dec 14}, pages = {1621-1633}, abstract = {

Pyrrolobenzodiazepines (PBDs) are naturally occurring DNA binding compounds that possess anti-tumor and anti-bacterial activity. Chemical modifications of PBDs can result in improved DNA binding, sequence specificity and enhanced efficacy. More recently, synthetic PBD monomers have shown promise as payloads for antibody drug conjugates and anti-bacterial agents. The precise mechanism of action of these PBD monomers and their role in causing DNA damage remains to be elucidated. Here we characterized the damage-inducing potential of two C8-linked PBD bi-aryl monomers in and investigated the strategies employed by cells to repair the same. We show that these compounds cause DNA damage and efficiently kill bacteria, in a manner comparable to the extensively used DNA cross-linking agent mitomycin-C (MMC). However, in stark contrast to MMC which employs a mutagenic lesion tolerance pathway, we implicate essential functions for error-free mechanisms in repairing PBD monomer-mediated damage. We find that survival is severely compromised in cells lacking nucleotide excision repair and to a lesser extent, in cells with impaired recombination-based repair. Loss of nucleotide excision repair leads to significant increase in double-strand breaks, underscoring the critical role of this pathway in mediating repair of PBD-induced DNA lesions. Together, our study provides comprehensive insights into how mono-alkylating DNA-targeting therapeutic compounds like PBD monomers challenge cell growth, and identifies the specific mechanisms employed by the cell to counter the same.

}, issn = {2632-8682}, doi = {10.1039/d2md00194b}, author = {Joseph, Asha Mary and Nahar, Kazi and Daw, Saheli and Hasan, Md Mahbub and Lo, Rebecca and Le, Tung B K and Rahman, Khondaker Miraz and Badrinarayanan, Anjana} } @article {117960, title = {Mechanistic Insights into the Functioning of a Two-Subunit GMP Synthetase, an Allosterically Regulated, Ammonia Channeling Enzyme}, journal = {BIOCHEMISTRY}, volume = {61}, year = {2022}, month = {09/2022}, pages = {1988-2006}, abstract = {

Guanosine 5 {\textquoteright}-monophosphate (GMP) synthetases, enzymes that catalyze the conversion of xanthosine 5 {\textquoteright}-mono-phosphate (XMP) to GMP, are composed of two different catalytic units, which are either two domains of a polypeptide chain or two subunits that associate to form a complex. The glutamine amidotransferase (GATase) unit hydrolyzes glutamine generating ammonia, and the ATP pyrophosphatase (ATPPase) unit catalyzes the formation of an AMP-XMP intermediate. The substrate-bound ATPPase allosterically activates GATase, and the ammonia thus generated is tunneled to the ATPPase active site where it reacts with AMP-XMP generating GMP. In ammonia channeling enzymes reported thus far, a tight complex of the two subunits is observed, while the interaction of the two subunits of Methanocaldococcus jannaschii GMP synthetase (MjGMPS) is transient with the underlying mechanism of allostery and substrate channeling largely unclear. Here, we present a mechanistic model encompassing the various steps in the catalytic cycle of MjGMPS based on biochemical experiments, crystal structure, and cross-linking mass spectrometry guided integrative modeling. pH dependence of enzyme kinetics establishes that ammonia is tunneled across the subunits with the lifetime of the complex being \<= 0.5 s. The crystal structure of the XMP-bound ATPPase subunit reported herein highlights the role of conformationally dynamic loops in enabling catalysis. The structure of MjGMPS derived using restraints obtained from cross-linking mass spectrometry has enabled the visualization of subunit interactions that enable allostery under catalytic conditions. We integrate the results and propose a functional mechanism for MjGMPS detailing the various steps involved in catalysis.

}, doi = {10.1021/acs.biochem.2c001511988}, author = {Shivakumaraswamy, Santosh and Kumar, Sanjeev and Bellur, Asutosh and Polisetty, Satya Dev and Balaram, Hemalatha} } @article {115053, title = {Mechanistic Investigations on N-C Bond Cleavages in Dibasic Peptides Containing Internal Lys and Arg Residues.}, journal = {J Am Soc Mass Spectrom}, year = {2022}, month = {2022 Jul 26}, abstract = {

The model nonapeptide AAARAAKAG* (* indicates amide) is used to explore N-C bond fragmentation under CID-MS conditions. Neighboring group participation and the effect of positioning of Lys and Arg residues on N-C bond cleavage is established using a library of synthetic peptide analogues. The importance of the Arg residue at position 4 and the to +3 spacing between Arg and Lys residues in determining the formation of the N-C bond cleaved product ions () is demonstrated by a comparative MS study of positional variants in analogue peptides. The effect of shortening of the Lys side chain has been established using ornithine (Orn) and diaminobutyric acid (Dab) analogues. The involvement of the Lys residue in mediating the N-C bond cleavage is further probed using N-dimethyl and isotopically labeled N lysine residues. MS experiments reveal that the ion originates from a doubly charged dehydrated ion [-18]. The mechanism of this unusual fragmentation process has been probed by using position 8 analogues (Gly, Ala, and Aib). A plausible mechanism is proposed for the origin of the ion, which involves C-terminus lactam formation followed by transannular cyclization and dehydration. The results presented in this study highlight the role of reactive side chain functionalities in promoting noncanonical fragmentation pathways.

}, issn = {1879-1123}, doi = {10.1021/jasms.2c00055}, author = {Kumar, Sanjeev and Venkatesha, M Achanna and Balaram, Padmanabhan} } @article {115012, title = {A Method for Assessing the Robustness of Protein Structures by Randomizing Packing Interactions.}, journal = {Front Mol Biosci}, volume = {9}, year = {2022}, month = {2022}, pages = {849272}, abstract = {

Many single-domain proteins are not only stable and water-soluble, but they also populate few to no intermediates during folding. This reduces interactions between partially folded proteins, misfolding, and aggregation, and makes the proteins tractable in biotechnological applications. Natural proteins fold thus, not necessarily only because their structures are well-suited for folding, but because their sequences optimize packing and fit their structures well. In contrast, folding experiments on the designed Top7 suggest that it populates several intermediates. Additionally, in protein design, where sequences are designed for natural and new non-natural structures, tens of sequences still need to be tested before success is achieved. Both these issues may be caused by the specific scaffolds used in design, i.e., some protein scaffolds may be more tolerant to packing perturbations and varied sequences. Here, we report a computational method for assessing the response of protein structures to packing perturbations. We then benchmark this method using designed proteins and find that it can identify scaffolds whose folding gets disrupted upon perturbing packing, leading to the population of intermediates. The method can also isolate regions of both natural and designed scaffolds that are sensitive to such perturbations and identify contacts which when present can rescue folding. Overall, this method can be used to identify protein scaffolds that are more amenable to whole protein design as well as to identify protein regions which are sensitive to perturbations and where further mutations should be avoided during protein engineering.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.849272}, author = {Yadahalli, Shilpa and Jayanthi, Lakshmi P and Gosavi, Shachi} } @article {108046, title = {Methodological approaches for estimating populations of the endangered dhole .}, journal = {PeerJ}, volume = {10}, year = {2022}, month = {2022}, pages = {e12905}, abstract = {

Large carnivores are important for maintaining ecosystem integrity and attract much research and conservation interest. For most carnivore species, estimating population density or abundance is challenging because they do not have unique markings for individual identification. This hinders status assessments for many threatened species, and calls for testing new methodological approaches. We examined past efforts to assess the population status of the endangered dhole (), and explored the application of a suite of recently developed models for estimating their populations using camera-trap data from India{\textquoteright}s Western Ghats. We compared the performance of Site-Based Abundance (SBA), Space-to-Event (STE), and Time-to-Event (TTE) models against current knowledge of their population size in the area. We also applied two of these models (TTE and STE) to the co-occurring leopard (), for which density estimates were available from Spatially Explicit Capture-Recapture (SECR) models, so as to simultaneously validate the accuracy of estimates for one marked and one unmarked species. Our review of literature (\ =\ 38) showed that most assessments of dhole populations involved crude indices (relative abundance index; RAI) or estimates of occupancy and area of suitable habitat; very few studies attempted to estimate populations. Based on empirical data from our field surveys, the TTE and SBA models overestimated dhole population size beyond ecologically plausible limits, but the STE model produced reliable estimates for both the species. Our findings suggest that it is difficult to estimate population sizes of unmarked species when model assumptions are not fully met and data are sparse, which are commonplace for most ecological surveys in the tropics. Based on our assessment, we propose that practitioners who have access to photo-encounter data on dholes across Asia test old and new analytical approaches to increase the overall knowledge-base on the species, and contribute towards conservation monitoring of this endangered carnivore.

}, issn = {2167-8359}, doi = {10.7717/peerj.12905}, author = {Punjabi, Girish A and Havm{\o}ller, Linnea Wors{\o}e and Havm{\o}ller, Rasmus Wors{\o}e and Ngoprasert, Dusit and Srivathsa, Arjun} } @article {115812, title = {Migration of active rings in porous media.}, journal = {Phys Rev E}, volume = {106}, year = {2022}, month = {2022 Jul}, pages = {014504}, abstract = {

Inspired by how the shape deformations in active organisms help them to migrate through disordered porous environments, we simulate active ring polymers in two-dimensional random porous media. Flexible and inextensible active ring polymers navigate smoothly through the disordered media. In contrast, semiflexible rings undergo transient trapping inside the pore space; the degree of trapping is inversely correlated with the increase in activity. We discover that flexible rings swell while inextensible and semiflexible rings monotonically shrink upon increasing the activity. Together, our findings identify the optimal migration of active ring polymers through porous media.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.106.014504}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {116182, title = {Molecular architecture of nucleosome remodeling and deacetylase sub-complexes by integrative structure determination.}, journal = {Protein Sci}, volume = {31}, year = {2022}, month = {2022 Sep}, pages = {e4387}, abstract = {

The nucleosome remodeling and deacetylase (NuRD) complex is a chromatin-modifying assembly that regulates gene expression and DNA damage repair. Despite its importance, limited structural information describing the complete NuRD complex is available and a detailed understanding of its mechanism is therefore lacking. Drawing on information from SEC-MALLS, DIA-MS, XLMS, negative-stain EM, X-ray crystallography, NMR spectroscopy, secondary structure predictions, and homology models, we applied Bayesian integrative structure determination to investigate the molecular architecture of three NuRD sub-complexes: MTA1-HDAC1-RBBP4, MTA1 -HDAC1-MBD3 , and MTA1-HDAC1-RBBP4-MBD3-GATAD2A [nucleosome deacetylase (NuDe)]. The integrative structures were corroborated by examining independent crosslinks, cryo-EM maps, biochemical assays, known cancer-associated mutations, and structure predictions from AlphaFold. The robustness of the models was assessed by jack-knifing. Localization of the full-length MBD3, which connects the deacetylase and chromatin remodeling modules in NuRD, has not previously been possible; our models indicate two different locations for MBD3, suggesting a mechanism by which MBD3 in the presence of GATAD2A asymmetrically bridges the two modules in NuRD. Further, our models uncovered three previously unrecognized subunit interfaces in NuDe: HDAC1 -MTA1 , MTA1 -MBD3 , and HDAC1 -MBD3 . Our approach also allowed us to localize regions of unknown structure, such as HDAC1 and MBD3 , thereby resulting in the most complete and robustly cross-validated structural characterization of these NuRD sub-complexes so far.

}, issn = {1469-896X}, doi = {10.1002/pro.4387}, author = {Arvindekar, Shreyas and Jackman, Matthew J and Low, Jason K K and Landsberg, Michael J and Mackay, Joel P and Viswanath, Shruthi} } @article {121149, title = {Molecular markers for early stratification of disease severity and progression in COVID-19.}, journal = {Biol Methods Protoc}, volume = {7}, year = {2022}, month = {2022}, pages = {bpac028}, abstract = {

COVID-19 infections have imposed immense pressure on the healthcare system of most countries. While the initial studies have identified better therapeutic and diagnostic approaches, the disease severity is still assessed by close monitoring of symptoms by healthcare professionals due to the lack of biomarkers for disease stratification. In this study, we have probed the immune and molecular profiles of COVID-19 patients at 48-h intervals after hospitalization to identify early markers, if any, of disease progression and severity. Our study reveals that the molecular profiles of patients likely to enter the host-immune response-mediated moderate or severe disease progression are distinct even in the early phase of infection when severe symptoms are not yet apparent. Our data from 37 patients suggest that at hospitalization, interleukins (IL6) (\>300\ pg/ml) and IL8 levels (\>200\ pg/ml) identify cytokine-dependent disease progression. Monitoring their levels will facilitate timely intervention using available immunomodulators or precision medicines in those likely to progress due to cytokine storm and help improve outcomes. Additionally, it will also help identify cytokine-independent progressive patients, not likely to benefit from immunomodulators or precision drugs.

}, issn = {2396-8923}, doi = {10.1093/biomethods/bpac028}, author = {Kashyap, Anusha and Sebastian, Savitha Anne and Krishnaiyer NarayanaSwamy, Sree Raksha and Raksha, KalyanKumar and Krishnamurthy, Hanumanthappa and Krishna, Bhuvana and D{\textquoteright}Souza, George and Idiculla, Jyothi and Vyas, Neha} } @article {123119, title = {A multitude of spots! Five new microendemic species of the Cnemaspis gracilis group (Squamata: Gekkonidae) from massifs in the Shevaroy landscape, Tamil Nadu, India}, journal = {Vertebrate Zoology}, volume = {72}, year = {2022}, month = {12/2022}, pages = {1137-1186}, abstract = {

South Asian Cnemaspis are one of the most diverse clades of gekkonids in South Asia with their highest diversity in the Western Ghats and Sri Lanka. These geckos include only a few nocturnal species and are largely diurnal or cathemeral and restricted to relatively cool habitats. One of the prominently diurnal subgroups in South Asian Cnemaspis is the bangara clade, which includes six species distributed in southern India on the eastern slopes of the Western Ghats, the southern Eastern Ghats and Palghat Gap. In this paper, we describe five more species of the bangara clade from the Shevaroyan landscape, including three from Kollimalai and one each from Yercaud and Pachaimalai, all in Tamil Nadu. These new species show 4.6{\textendash}19.7 \% uncorrected sequence divergence on the mitochondrial ND2 gene from each other and known species of the bangara clade and are morphologically diagnosable in body size, the number of paravertebral tubercles between limb insertions, the number of dorsal tubercle rows, the number of ventral scale rows across the belly, the number of femoral and precloacal pores and poreless scales separating these series, and aspects of colouration. The discovery of these five new species adds to the growing discoveries of cool-adapted species in southern India outside the Western Ghats and highlights the role of sky-islands in diversification. The Shevaroyan landscape shows high levels of microendemism with eight species distributed in an area of \< 2000 km2, and all these species restricted to much smaller areas of actual distribution. With an area of \< 500 km2 respectively, the massif of Pachaimalai has a single endemic and the massifs of Yercaud and Kollimalai have three endemic Cnemaspis species each.

}, doi = {doi: 10.3897/vz.72.e94799 }, author = {Agarwal, I and Thackeray, T and Khandekar, A} } @article {103407, title = {Native State Hydrogen Exchange-Mass Spectrometry Methods to Probe Protein Folding and Unfolding.}, journal = {Methods Mol Biol}, volume = {2376}, year = {2022}, month = {2022}, pages = {143-159}, abstract = {

Native state hydrogen exchange (HX) methods provide high-resolution structural data on the rare and transient opening motions in proteins under native conditions. Mass spectrometry-based HX methods (HX-MS) have gained popularity because of their ability to delineate population distributions, which allow a direct determination of the mechanism of inter conversion of the partially folded states under native conditions. Various technological advancements have provided further impetus to the development of HX-MS-based experiments to study protein folding. Classical HX-MS studies use proteolytic digestion to produce fragments of the protein subsequent to HX in solution, in order to obtain structural data. New chemical fragmentation methods, which achieve the same result as proteolysis and cause minimal change to the HX pattern in the protein, provide an attractive alternative to proteolysis. Moreover, when used in conjunction with proteolysis, chemical fragmentation methods have significantly increased the structural resolution afforded by HX-MS studies, even bringing them at par with the single amino acid resolution observed in NMR-based measurements. Experiments based on one such chemical fragmentation method, electron transfer dissociation (ETD), are described in this chapter. The ETD HX-MS method is introduced using data from a protein which is inherently resistant to proteolytic digestion as example of how such an experiment can provide high-resolution structural data on the folding-unfolding transitions of the protein under native conditions.

}, issn = {1940-6029}, doi = {10.1007/978-1-0716-1716-8_8}, author = {Malhotra, Pooja and Udgaonkar, Jayant B} } @article {121921, title = {Near-chromosomal de novo assembly of Bengal tiger genome reveals genetic hallmarks of apex predation. }, journal = {Gigascience}, volume = {12:giac112}, year = {2022}, month = {12/2022}, abstract = {

The tiger, a poster child for conservation, remains an endangered apex predator. Continued survival and recovery will require a comprehensive understanding of genetic diversity and the use of such information for population management. A high-quality tiger genome assembly will be an important tool for conservation genetics, especially for the Indian tiger, the most abundant subspecies in the wild. Here, we present high-quality near-chromosomal genome assemblies of a female and a male wild Indian tiger (Panthera tigris tigris). Our assemblies had a scaffold N50 of \>140 Mb, with 19 scaffolds corresponding to the 19 numbered chromosomes, containing 95\% of the genome. Our assemblies also enabled detection of longer stretches of runs of homozygosity compared to previous assemblies, which will help improve estimates of genomic inbreeding. Comprehensive genome annotation identified 26,068 protein-coding genes, including several gene families involved in key morphological features such as the teeth, claws, vision, olfaction, taste, and body stripes. We also identified 301 microRNAs, 365 small nucleolar RNAs, 632 transfer RNAs, and other noncoding RNA elements, several of which are predicted to regulate key biological pathways that likely contribute to the tiger{\textquoteright}s apex predatory traits. We identify signatures of positive selection in the tiger genome that are consistent with the Panthera lineage. Our high-quality genome will enable use of noninvasive samples for comprehensive assessment of genetic diversity, thus supporting effective conservation and management of wild tiger populations.

}, doi = {10.1093/gigascience/giac112.}, author = {Shukla, H and Suryamohan, K and Khan, A and Mohan, K and Perumal, RC and Mathew, OK and Menon, R and Dixon, MD and Muraleedharan, M and Kuriakose, B and Michael, S and Krishnankutty, SP and Zachariah, A and Seshagiri, S and Ramakrishnan, U} } @article {117970, title = {Neurological Consequences of Sphingosine Phosphate Lyase Insufficiency.}, journal = {Front Cell Neurosci}, volume = {16}, year = {2022}, month = {2022}, pages = {938693}, abstract = {

In 2017, an inborn error of metabolism caused by recessive mutations in was discovered. The disease features steroid-resistant nephrotic syndrome, adrenal insufficiency, and neurological defects. The latter can include sensorineural hearing loss, cranial nerve defects, peripheral neuropathy, abnormal brain development, seizures and/or neurodegeneration. encodes the pyridoxal-5{\textquoteright}-phosphate (PLP) dependent enzyme sphingosine phosphate lyase (SPL), and the condition is now referred to as SPL insufficiency syndrome (SPLIS). SPL catalyzes the final step in the degradative pathway of sphingolipids in which the bioactive sphingolipid sphingosine-1-phosphate (S1P) is irreversibly degraded to a long chain aldehyde and phosphoethanolamine (PE). SPL guards the only exit point for sphingolipid metabolism, and its inactivation leads to accumulation of various types of sphingolipids which have biophysical roles in plasma membrane rafts and myelin, and signaling roles in cell cycle progression, vesicular trafficking, cell migration, and programmed cell death. In addition, the products of the SPL reaction have biological functions including regulation of autophagic flux, which is important in axonal and neuronal integrity. In this review, the neurological manifestations of SPLIS will be described, and insights regarding the neurological consequences of SPL insufficiency from the study of brain-specific SPL knockout mice and SPL mutants will be summarized.

}, issn = {1662-5102}, doi = {10.3389/fncel.2022.938693}, author = {Atreya, Krishan B and Saba, Julie D} } @article {105471, title = {A new ancient lineage of ablepharine skinks (Sauria: Scincidae) from eastern Himalayas with notes on origin and systematics of the group}, journal = {PeerJ}, volume = {10}, year = {2022}, month = {01/2022}, pages = {e12800}, abstract = {

The Himalayas represent a renowned biodiversity hotspot and an important biogeographic realm that has influenced origin and diversification of multiple taxa. A recent herpetological investigation of the eastern Himalayas of the Indian state of Arunachal Pradesh led to the discovery of a unique lineage of ablepharine skink, which is herein described as a new genus along with a new species. The findings are based an integrated taxonomic approach incorporating data from external morphology, microCT scans of the skull and molecular data. The molecular phylogeny of ablepharine skinks is also presented that suggests taxonomic amendments. Discovery of this unique lineage of skinks further highlights the biogeographic importance of the eastern Himalayas as a source for origin of several relic biota.

}, doi = {10.7717/peerj.12800}, author = {Mirza, Zeeshan A and Bragin, Andrey M. and Bhosale, Harshal and Gowande, Gaurang and Patel, Harshil and Poyarkov, Nikolay A.} } @article {111039, title = {A new cryptic species of green pit viper of the genus Trimeresurus Lac{\'e}p{\`e}de, 1804 (Serpentes, Viperidae) from northeast India.}, journal = {PLoS One}, volume = {17}, year = {2022}, month = {2022}, pages = {e0268402}, abstract = {

A new cryptic species of green pit viper is described from northeast India, based on specimens collected from the state of Mizoram and Meghalaya. The new species is a member of the subgenus Viridovipera and is sister to Trimeresurus medoensis based on molecular data for mitochondrial cytochrome b gene, whereas resembles Trimeresurus gumprechti morphologically. A combination of characters helps delimit the new species from its congeners. Description of the new species highlights the need for dedicated surveys across northeast India to document its reptilian diversity, as this represents the third new species of the genus to be described in the past three years.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0268402}, author = {Rathee, Yashpal Singh and Purkayastha, Jayaditya and Lalremsanga, Hmar Tlawmte and Dalal, Siddharth and Biakzuala, Lal and Muansanga, Lal and Mirza, Zeeshan A} } @article {121913, title = {New Genus and Two New Species of Semiterrestrial Crabs (Decapoda: Brachyura: Gecarcinucidae) from the Southern Western Ghats, India.}, journal = {Zool Stud}, volume = {61}, year = {2022}, month = {2022}, pages = {e49}, abstract = {

One new genus and two new species of semiterrestrial freshwater crabs are described from the Southern Western Ghats mountain range in India: gen., sp. nov. and sp. nov. The carapace of n. gen. is superficially similar to and described from the same region, but it can be distinguished from in having no visible postorbital cristae, complete sutures between male thoracic sternites 2 and 3, the possession of a triangular male pleon and the elongate terminal segment of the male first gonopod; and from by the presence of a long flagellum on the exopod of the third maxilliped, a complete suture separating male thoracic sternites 2 and 3, and its triangular male pleon. sp. nov. can easily be distinguished from congeners in possessing a distinctly more slender and elongate male first gonopod.

}, issn = {1810-522X}, doi = {10.6620/ZS.2022.61-49}, author = {Raj, Smrithy and Kumar, Appukuttannair Biju and Ng, Peter K L} } @article {109299, title = {A new species of bent-toed geckos of the genus Cyrtodactylus Gray, 1827 from western Arunachal Pradesh, India}, journal = {HERPETOZOA }, volume = {35}, year = {2022}, month = {03/2022}, pages = {65-76}, abstract = {

A new species of bent-toed geckos of the genus Cyrtodactylus is described from western Arunachal Pradesh. The new species is a member of the Indo-Burma clade and is embedded within the {\textquoteleft}peguensis" group, a relationship deduced contingent on a partial fragment of mitochondrial NADH subunit 2 gene. Cyrtodactylus kamengensis sp. nov. is morphologically similar to C. himalayicus from which it differs in bearing a distinct ventrolateral fold and 6-8 basal lamellae on digit IV of pes. Genetically, the new species is sister to the Indian lineage of the {\textquoteleft}peguensis" group containing C. bhupathyi and C. gubernatoris. The Indian lineage of the {\textquoteleft}peguen-sis" group diverged from its Burmese relatives during the mid-Oligocene likely followed by the beginning of the Himalayan uplift, highlighting the role of the Himalayas in the diversification of biota.

}, doi = {10.3897/herpetozoa.35.e80610}, author = {Mirza, Zeeshan A and Bhosale, Harshal and Ansari, Faizan and Phansalkar, Pushkar and Sawant, Mandar and Gowande, Gaurang and Patel, Harshil} } @article {110445, title = {A new species of Conothele Thorell, 1878 (Aranei Halonoproctidae) from the northern Western Ghats, India}, journal = {ARTHROPODA SELECTA}, volume = {31}, year = {2022}, month = {03/2022}, pages = {79-89}, abstract = {

The trap-door spider Conothele ogalei sp.n. is described from the holotype male and paratype females collected in Amboli (Maharashtra, India). This is the first report of the genus Conothele from the northern Western Ghats and also the first description of a male congener from India. The data on the natural history of the new species as well as notes on the diversity and distribution of Indian Conothele spp. are provided.

}, doi = {10.15298/arthsel.31.1.09}, author = {Sanap, Rajesh and Pawar, Swapnil and Joglekar, Anuradha and Khandekar, Akshay} } @article {108050, title = {Nitrate-dependent regulation of miR444-OsMADS27 signaling cascade controls root development in rice.}, journal = {J Exp Bot}, year = {2022}, month = {2022 Mar 04}, abstract = {

Nitrate is an important nutrient and a key signaling molecule for plant development. A number of transcription factors involved in the process of nitrate response and their regulatory mechanisms have been identified. However, little is known about the nitrate sensor transcription factors and their regulatory mechanisms among crop plants. In this study, we identified functions of a nitrate-responsive miR444:MADS-box transcription factor OsMADS27 module and its downstream targets mediating rice root growth and stress responses. Transgenic rice plants expressing miR444 target mimic improved rice root growth. Although miR444 has the potential to target multiple genes, we identified OsMADS27 as the major miR444 target that regulates the expression of nitrate transporters, as well as several key genes including expansins and those associated with auxin signaling promote root growth. In agreement with this, overexpression of miRNA-resistant OsMADS27 improved root development and tolerance to stresses, while its silencing suppressed root growth. OsMADS27-mediated a robust stress tolerance in plants through its ability to bind to the promoters of specific stress regulators as observed in ChIP-Seq analysis. Our results provide evidence of nitrate-dependent miR444-OsMADS27 signaling cascade involved in the regulation of rice root growth as well as its surprising role in stress responses.

}, issn = {1460-2431}, doi = {10.1093/jxb/erac083}, author = {Pachamuthu, Kannan and Vivek Hari Sundar and Narjala, Anushree and Singh, Rahul R and Das, Soumita and Avik Pal, Harshith C Y and Shivaprasad, Padubidri V} } @article {108043, title = {Notch1 Modulation of Cellular Calcium Regulates Mitochondrial Metabolism and Anti-Apoptotic Activity in T-Regulatory Cells.}, journal = {Front Immunol}, volume = {13}, year = {2022}, month = {2022}, pages = {832159}, abstract = {

As the major hub of metabolic activity and an organelle sequestering pro-apoptogenic intermediates, mitochondria lie at the crossroads of cellular decisions of death and survival. Intracellular calcium is a key regulator of these outcomes with rapid, uncontrolled uptake into mitochondria, activating pro-apoptotic cascades that trigger cell death. Here, we show that calcium uptake and mitochondrial metabolism in murine T-regulatory cells (Tregs) is tuned by Notch1 activity. Based on analysis of Tregs and the HEK cell line, we present evidence that modulation of cellular calcium dynamics underpins Notch1 regulation of mitochondrial homeostasis and consequently anti-apoptotic activity. Targeted siRNA-mediated ablations reveal dependency on molecules controlling calcium release from the endoplasmic reticulum (ER) and the chaperone, glucose-regulated protein 75 (Grp75), the associated protein Voltage Dependent Anion Channel (VDAC)1 and the Mitochondrial Calcium Uniporter (MCU), which together facilitate ER calcium transfer and uptake into the mitochondria. Endogenous Notch1 is detected in immune-complexes with Grp75 and VDAC1. Deficits in mitochondrial oxidative and survival in Notch1 deficient Tregs, were corrected by the expression of recombinant Notch1 intracellular domain, and in part by recombinant Grp75. Thus, the modulation of calcium dynamics and consequently mitochondrial metabolism underlies Treg survival in conditions of nutrient stress. This work positions a key role for Notch1 activity in these outcomes.

}, issn = {1664-3224}, doi = {10.3389/fimmu.2022.832159}, author = {Saini, Neetu and Lakshminarayanan, Sowmya and Kundu, Priyanka and Sarin, Apurva} } @article {111036, title = {Oviposition Preference and Performance of a Specialist Herbivore Is Modulated by Natural Enemies, Larval Odors, and Immune Status.}, journal = {J Chem Ecol}, year = {2022}, month = {2022 May 23}, abstract = {

Insect herbivores frequently must balance host plant quality and the risk of attack by their natural enemies when making oviposition decisions. Yet, which factor is more important remains unresolved in plant-insect ecology. Here, we report the oviposition preference and larval performance of the brassicaceous specialist Plutella xylostella, in the context of plant quality (cabbage Brassica oleracea vs. mustard B. juncea) and associated natural enemies. Despite the greater larval weight and adult lifespan on cabbage, ovipositing females strongly preferred mustard. Both the egg parasitoid Trichogrammatoidea bactrae and the larval ectoparasitoid Bracon brevicornis are more likely to attack P. xylostella that feed on cabbage; thus, mustard represents enemy-reduced space from these two parasitoids. However, larval diet had no impact on the parasitism rate of specialist Cotesia vestalis. Feeding on mustard improved larval immune responses. The total hemocyte number, diversity, and phenoloxidase activity were higher in mustard-fed larvae which increased their survival against the entomopathogen, Bacillus thuringiensis. Interestingly, host plants altered the larval body odor profile. Mustard-fed larvae emitted allyl isothiocyanate (AITC) and butyl isothiocyanate (BITC) while cabbage-fed larvae emitted dimethyl disulphide (DMDS) and dimethyl trisulphide (DMTS) that served as short-range cues for larval parasitoids. For B. brevicornis, host body odor guided oviposition choice was crucial as their fitness was affected by the host larval diet. Although C. vestalis showed a clear preference towards volatiles emitted by mustard fed larvae, their fitness was unaltered. Taken together, our results illustrate that P. xylostella prefers to lay eggs on mustard plants providing enemy-reduced space from some, but not all, natural enemies.

}, issn = {1573-1561}, doi = {10.1007/s10886-022-01363-5}, author = {Ghosh, Enakshi and Sasidharan, Aswathi and Ode, Paul J and Venkatesan, Radhika} } @article {109312, title = {PASS2.7: a database containing structure-based sequence alignments and associated features of protein domain superfamilies from SCOPe.}, journal = {Database (Oxford)}, volume = {2022}, year = {2022}, month = {2022 Apr 12}, abstract = {

Sequence alignments are models that capture the structural, functional and evolutionary relationships between proteins. Structure-guided sequence alignments are helpful in the case of distantly related proteins with poor sequence identity, thus rendering routine sequence alignment methods ineffective. Protein Alignment organized as Structural Superfamilies or PASS2 database provides such sequence alignments of protein domains within a superfamily as per the Structural Classification of Proteins extended (SCOPe) database. The current update of PASS2 (i.e. PASS2.7) is following the latest release of SCOPe (2.07) and we provide data for 14 323 protein domains that are \<40\% identical and are organized into 2024 superfamilies. Several useful features derived from the alignments, such as conserved secondary structural motifs, HMMs and residues conserved across the superfamily, are also reported. Protein domains that are deviant from the rest of the members of a superfamily may compromise the quality of the alignment, and we found this to be the case in \~{}7\% of the total superfamilies we considered. To improve the alignment by objectively identifying such {\textquoteright}outliers{\textquoteright}, in this update, we have used a k-means-based unsupervised machine learning method for clustering superfamily members, where features provided were length of domains aligned, Cα-RMSD derived from the rigid-body superposition of all members and gaps contributed to the alignment by each domain. In a few cases, we have split the superfamily as per the clusters predicted and provided complete data for each cluster. A new feature included in this update is absolutely conserved interactions (ACIs) between residue backbones and side chains, which are obtained by aligning protein structure networks using structure-guided sequence alignments of superfamilies. ACIs provide valuable information about functionally important residues and the structure-function relationships of proteins. The ACIs and the corresponding conserved networks for backbone and sidechain have been marked on the superimposed structure separately.

DATABASE URL: The updated version of the PASS2 database is available at http://caps.ncbs.res.in/pass2/.

}, keywords = {Databases, Protein, Protein Domains, Protein Structure, Tertiary, Proteins, Sequence Alignment}, issn = {1758-0463}, doi = {10.1093/database/baac025}, author = {Bhattacharyya, Teerna and Nayak, Soumya and Goswami, Smit and Gadiyaram, Vasundhara and Mathew, Oommen K and Sowdhamini, Ramanathan} } @article {106551, title = {Phosphoproteome of signaling by ErbB2 in ovarian cancer cells.}, journal = {Biochim Biophys Acta Proteins Proteom}, year = {2022}, month = {2022 Feb 11}, pages = {140768}, abstract = {

The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 in ovarian cancer cells. The ErbB2 specific proteins identified in SKOV-3 cells were Myristoylated alanine-rich C-kinase substrate, Protein capicua homolog, Protein peptidyl isomerase G, Protein PRRC2C, Chromobox homolog1 and PRP4 homolog. We have evaluated three phosphoproteins PKM2, Aldose reductase and MARCKS in SKOV-3 cells. We observed that PKM2 was phosphorylated by EGF but was not inhibited by Lapatinib and CP724714. The activity of aldose reductase in reducing NADPH as a substrate was significantly higher in EGF stimulated cells which was inhibited by Lapatinib and CP724714 but not by Geftinib (EGFR inhibitor). MARCKS was phosphorylated on stimulation of SKOV-3 cells with EGF that was inhibited by Lapatinib and CP724714 which was dependent on the kinase activity of ErbB2. These results have identified phosphoproteins that are specific to ErbB2 which have not been previously reported and sets the basis for future experiments.

}, issn = {1878-1454}, doi = {10.1016/j.bbapap.2022.140768}, author = {Sidhanth, C and Bindhya, S and Krishnapriya, S and Manasa, P and Shabna, A and Alifia, J and Patole, C and Kumar, V and Garg, M and Ganesan, T S} } @article {123116, title = {Pollination inaccuracy: estimating male fitness in the movement-assisted dichogamous species Clerodendrum infortunatum}, journal = {Evolutionary Ecology}, year = {2022}, month = {12/2022}, abstract = {

In hermaphroditic dichogamous species, sporophylls are separated in time. However, the separation of sporophylls can lead to pollination inaccuracy, especially in movement-assisted dichogamy, where sporophylls alter their position over time. Is pollination inaccuracy minimised by the second sporophyll taking the exact position of the first? We address this question in Clerodendrum infortunatum, a movement-assisted dichogamous species. We made predictions from optimality arguments, and tested these by measuring sporophyll angles over time, by experimentally manipulating flowers, and by estimating correlates of the resultant fitness, taking into account pollen export, pollination inaccuracy and the resultant total pollen delivered. Contrary to expectation, anthers do not have a fixed position in the male phase, and pollination inaccuracy is high. Further, when the number of pollen grains on anthers is highest, anthers are paradoxically not positioned at the pollen export peak. Also, pollen export and pollen deposition peaks do not align. Despite this seeming maladaptiveness, the starting position of the anthers is, in fact, very close to the theoretical optimum, which results in the highest overall male fitness, measured as the total pollen delivered over the entire male phase. Instead of a simple positional exchange of sporophylls, stamens display a more complicated dynamic strategy that appears close to optimal even though naive measures of pollination inaccuracy are high.

}, doi = {10.1007/s10682-022-10221-5}, author = {Mukhopadhyay, A and Quader, Suhel} } @article {123114, title = {{\textquoteleft}Priming{\textquoteright} protects Piper nigrum L. from Phytophthora capsici through reinforcement of phenylpropanoid pathway and possible enhancement of Piperine biosynthesis }, journal = {Front. Plant Sci.}, volume = {13}, year = {2022}, month = {12/2022}, abstract = {

Piper nigrum L. (black pepper), a woody perennial spice crop indigenous to India is positioned at the phylogenetically unique basal lineage of angiosperms. Cultivation of this major spice crop is constrained by rampant fungal and viral infections leading to a lack of disease-free planting material. The major disease that poses severe threat to P. nigrum plantations and nurseries is {\textquoteleft}quick wilt{\textquoteright} caused by the oomycete Phytophthora capsici, which affects the leaf, stem, spike, collar and root. In this paper, we report the consequence of priming in modulating Piper nigrum defense against Phytophthora capsici. Glycol Chitosan (GC) was used to infiltrate detached leaves of mature P. nigrum plants. It was observed that pre-treatment of GC for 24 hours resulted in significant reduction of disease symptoms in infected leaves, as evidenced by the marked decrease in the size of lesions, and also delayed the appearance of symptoms up to 72 hpi. Experiments repeated in P. nigrum seedlings under controlled growth conditions indicate that delayed disease symptoms of GC pre-treated leaves do not spread to healthy uninfiltrated leaves suggesting a priming-associated systemic defense response. An ROS-mediated manifestation of Hypersensitive Response (HR) induced by Chitosan was also evident in pre-treated leaves. A corresponding visual indication of increased lignification was observed, which correlated with an enhanced lignin content of GC-treated leaves. Enhanced callose deposition was also apparent in GC infiltrated leaves, establishing a stimulatory effect of GC in triggering HR through ROS production, enhanced lignification and callose deposition. Key genes of the core phenylpropanoid and isoprenoid pathways along with major defense signalling pathway genes of P. nigrum, including pathogenesis-related genes and hormone signalling genes showed significant transcript enrichment consequential to GC treatment. A significant quantitative enhancement in Piperine content was evident in GC-infiltrated leaves. The systemic nature of priming on disease protection was established through experiments conducted in rooted cuttings monitored for 30 days after disease infection. This is the first report that provides strong molecular evidence endorsing the twofold advantage of defense priming in P. nigrum by improving crop protection with a concomitant enhancement in Piperine biosynthesis.

}, doi = {10.3389/fpls.2022.1072394}, author = {Indu, M and Meera, B and Sivakumar, K and Mahadevan, C and Shafi, K and Nagarathnam, B and Sowdhamini, R and Sakuntala, M} } @article {115255, title = {PrISM: Precision for Integrative Structural Models}, journal = {Bioinformatics}, year = {2022}, month = {06/2022}, abstract = {

Motivation: A single precision value is currently reported for an integrative model. However, precision may vary for different regions of an integrative model owing to varying amounts of input information.

Results: We develop PrISM (Precision for Integrative Structural Models), to efficiently identify high and low-precision regions for integrative models.

}, doi = {10.1093/bioinformatics/btac400 }, author = {Ullanat, V and Kasukurthi, N and Viswanath, Shruthi} } @article {109939, title = {Profiling, monitoring and conserving caterpillar fungus in the Himalayan region using anchored hybrid enrichment markers.}, journal = {Proc Biol Sci}, volume = {289}, year = {2022}, month = {2022 Apr 27}, pages = {20212650}, abstract = {

The collection of caterpillar fungus accounts for 50-70\% of the household income of thousands of Himalayan communities and has an estimated market value of $5-11 billion across Asia. However, Himalayan collectors are at multiple economic disadvantages compared with collectors on the Tibetan Plateau because their product is not legally recognized. Using a customized hybrid-enrichment probe set and market-grade caterpillar fungus (with samples up to 30 years old) from 94 production zones across Asia, we uncovered clear geography-based signatures of historical dispersal and significant isolation-by-distance among caterpillar fungus hosts. This high-throughput approach can readily distinguish samples from major production zones with definitive geographical resolution, especially for samples from the Himalayan region that form monophyletic clades in our analysis. Based on these results, we propose a two-step procedure to help local communities authenticate their produce and improve this multi-national trade-route without creating opportunities for illegal exports and other forms of economic exploitation. We argue that policymakers and conservation practitioners must encourage the fair trade of caterpillar fungus in addition to sustainable harvesting to support a trans-boundary conservation effort that is much needed for this natural commodity in the Himalayan region.

}, keywords = {Asia, Fungi, Geography}, issn = {1471-2954}, doi = {10.1098/rspb.2021.2650}, author = {Wang, Zhengyang and Da, Wa and Negi, Chandra Singh and Ghimire, Puspa Lal and Wangdi, Karma and Yadav, Pramod K and Pubu, Zhuoma and Lama, Laiku and Yarpel, Kuenga and Maunsell, Sarah C and Liu, Yong and Kunte, Krushnamegh and Bawa, Kamaljit S and Yang, Darong and Pierce, Naomi E} } @article {115034, title = {Progressing Towards a Human-Centric Approach in Cancer Research.}, journal = {Front Oncol}, volume = {12}, year = {2022}, month = {2022}, pages = {896633}, abstract = {

Despite the advancement in research methodologies and technologies for cancer research, there is a high rate of anti-cancer drug attrition. In this review, we discuss different conventional and modern approaches in cancer research and how human-centric models can improve on the voids conferred by more traditional animal-centric models, thereby offering a more reliable platform for drug discovery. Advanced three-dimensional cell culture methodologies, along with computational analysis form the core of human-centric cancer research. This can provide a holistic understanding of the research problems and help design specific and accurate experiments that could lead to the development of better cancer therapeutics. Here, we propose a new human-centric research roadmap that promises to provide a better platform for cancer research and drug discovery.

}, issn = {2234-943X}, doi = {10.3389/fonc.2022.896633}, author = {Parekh, Aditya and Das, Subhayan and Das, Chandan K and Mandal, Mahitosh} } @article {123122, title = {Protein as evolvable functionally constrained amorphous matter.}, journal = {J Biosci}, volume = {47}, year = {2022}, month = {2022}, abstract = {

We explore current ideas around the representation of a protein as an amorphous material, in turn represented by an abstract graph G with edges weighted by elastic stiffnesses. By embedding this graph in physical space, we can map every graph to a spectrum of conformational fluctuations and responses (as a result of, say, ligandbinding). This sets up a {\textquoteright}genotype-phenotype{\textquoteright} map, which we use to evolve the amorphous material to select for fitness. Using this, we study the emergence of allosteric interaction, hinge joint, crack formation and a slide bolt in functional proteins such as adenylate kinase, HSP90, calmodulin and GPCR proteins. We find that these emergent features are associated with specific geometries and mode spectra of floppy or liquid-like regions. Our analysis provides insight into understanding the architectural demands on a protein that enable a prescribed function and its stability to mutations.

}, keywords = {Mutation}, issn = {0973-7138}, author = {Tripathy, Madhusmita and Srivastava, Anand and Sastry, Srikanth and Rao, Madan} } @article {117963, title = {Rapid brain development and reduced neuromodulator titres correlate with host shifts in .}, journal = {R Soc Open Sci}, volume = {9}, year = {2022}, month = {2022 Sep}, pages = {220962}, abstract = {

Host shifts are considered a key generator of insect biodiversity. For insects, adaptation to new host plants often requires changes in larval/pupal development and adult behavioural preference toward new hosts. Neurochemicals play key roles in both development and behaviour and therefore provide a potential source for such synchronization. Here, we correlated life-history timing, brain development and corresponding levels of 14 neurochemicals in (Diptera: Tephritidae), a species undergoing ecological speciation through an ongoing host shift from hawthorn to apple fruit. These races exhibit differences in pupal diapause timing as well as adult behavioural preference with respect to their hosts. This difference in behavioural preference is coupled with differences in neurophysiological response to host volatiles. We found that apple race pupae exhibited adult brain morphogenesis three weeks faster after an identical simulated winter than the hawthorn race, which correlated with significantly lower titres of several neurochemicals. In some cases, particularly biogenic amines, differences in titres were reflected in the mature adult stage, when host preference is exhibited. In summary, life-history timing, neurochemical titre and brain development can be coupled in this speciating system, providing new hypotheses for the origins of new species through host shifts.

}, issn = {2054-5703}, doi = {10.1098/rsos.220962}, author = {Kharva, Hinal and Feder, Jeffrey L and Hahn, Daniel A and Olsson, Shannon B} } @article {113537, title = {Recommendations for empowering early career researchers to improve research culture and practice.}, journal = {PLoS Biol}, volume = {20}, year = {2022}, month = {2022 Jul 07}, pages = {e3001680}, abstract = {

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3001680}, author = {Kent, Brianne A and Holman, Constance and Amoako, Emmanuella and Antonietti, Alberto and Azam, James M and Ballhausen, Hanne and Bediako, Yaw and Belasen, Anat M and Carneiro, Clarissa F D and Chen, Yen-Chung and Compeer, Ewoud B and Connor, Chelsea A C and Cr{\"u}well, Sophia and Debat, Humberto and Dorris, Emma and Ebrahimi, Hedyeh and Erlich, Jeffrey C and Fern{\'a}ndez-Chiappe, Florencia and Fischer, Felix and Gazda, Ma{\l}gorzata Anna and Glatz, Toivo and Grabitz, Peter and Heise, Verena and Kent, David G and Lo, Hung and McDowell, Gary and Mehta, Devang and Neumann, Wolf-Julian and Neves, Kleber and Patterson, Mark and Penfold, Naomi C and Piper, Sophie K and Puebla, Iratxe and Quashie, Peter K and Quezada, Carolina Paz and Riley, Julia L and Rohmann, Jessica L and Saladi, Shyam and Schwessinger, Benjamin and Siegerink, Bob and Stehlik, Paulina and Tzilivaki, Alexandra and Umbers, Kate D L and Varma, Aalok and Walavalkar, Kaivalya and de Winde, Charlotte M and Zaza, Cecilia and Weissgerber, Tracey L} } @article {115047, title = {Reconstitution of Membrane-tethered Minimal Actin Cortices on Supported Lipid Bilayers.}, journal = {J Vis Exp}, year = {2022}, month = {2022 Jul 12}, abstract = {

The surface of a living cell provides a versatile active platform for numerous cellular processes, which arise from the interplay of the plasma membrane with the underlying actin cortex. In the past decades, reconstituted, minimal systems based on supported lipid bilayers in combination with actin filament networks have proven to be very instrumental in unraveling basic mechanisms and consequences of membrane-tethered actin networks, as well as in studying the functions of individual membrane-associated proteins. Here, we describe how to reconstitute such active composite systems in vitro that consist of fluid supported lipid bilayers coupled via membrane-associated actin-binding proteins to dynamic actin filaments and myosin motors that can be readily observed via total internal reflection fluorescence microscopy. An open-chamber design allows one to assemble the system in a step-by-step manner and to systematically control many parameters such as linker protein concentration, actin concentration, actin filament length, actin/myosin ratio, as well as ATP levels. Finally, we discuss how to control the quality of the system, how to detect and troubleshoot commonly occurring problems, and some limitations of this system in comparison with the living cell surface.

}, keywords = {Actin Cytoskeleton, Actins, Cell Membrane, Lipid Bilayers, Myosins}, issn = {1940-087X}, doi = {10.3791/63968}, author = {K{\"o}ster, Darius Vasco and Bhat, Abrar and Talluri, Sankarshan and Mayor, Satyajit} } @inbook {116718, title = {Recruitment of Motoneurons.}, booktitle = {Vertebrate Motoneurons (Series: Advances in Neurobiology)}, volume = {28}, number = {28}, year = {2022}, pages = {169-190}, publisher = {Springer}, organization = {Springer}, abstract = {

Beginning about half a century ago, the rules that determine how motor units are recruited during movement have been deduced. These classical experiments led to the formulation of the {\textquoteright}size principle{\textquoteright}. It is now clear that motoneuronal size is not the only indicator of recruitment order. In fact, motoneuronal passive, active and synaptic conductances are carefully tuned to achieve sequential recruitment. More recent studies, over the last decade or so, show that the premotor circuitry is also functionally specialized and differentially recruited. Modular sub networks of interneurons and their post-synaptic motoneurons have been shown to drive movements with varying intensities. In addition, these modular networks are under the influence of neuromodulators, which are capable of acting upon multiple motor and premotor targets, thereby altering behavioral outcomes. We discuss the recruitment patterns of motoneurons in light of these new and exciting studies.

}, keywords = {Humans, Interneurons, Motor Neurons, Movement}, isbn = {9783031071669}, doi = {10.1007/978-3-031-07167-6_8}, author = {Thirumalai, Vatsala and Jha, Urvashi} } @article {113538, title = {Replication-dependent organisation constrains positioning of long DNA repeats in bacterial genomes.}, journal = {Genome Biol Evol}, year = {2022}, month = {2022 Jul 01}, abstract = {

Bacterial genome organisation is primarily driven by chromosomal replication from a single origin of replication. However chromosomal rearrangements, which can disrupt such organisation, are inevitable in nature. Long DNA repeats are major players mediating rearrangements, large and small, via homologous recombination. Since changes to genome organisation affect bacterial fitness - and more so in fast-growing than slow-growing bacteria - and are under selection, it is reasonable to expect that genomic positioning of long DNA repeats is also under selection. To test this, we identified identical DNA repeats of at least 100 base pairs across \~{}6,000 bacterial genomes and compared their distribution in fast and slow-growing bacteria. We found that long identical DNA repeats are distributed in a non-random manner across bacterial genomes. Their distribution differs in their overall number, orientation and proximity to the origin of replication, between fast and slow-growing bacteria. We show that their positioning - which might arise from a combination of the processes that produce repeats and selection on rearrangements that recombination between repeat elements might cause - permits less disruption to the replication-dependent genome organisation of bacteria compared to random suggesting it as a major constraint to positioning of long DNA repeats.

}, issn = {1759-6653}, doi = {10.1093/gbe/evac102}, author = {Malhotra, Nitish and Seshasayee, Aswin Sai Narain} } @article {104418, title = {Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy.}, journal = {J Med Genet}, volume = {59}, year = {2022}, month = {2021 Dec 16}, pages = {984-992}, abstract = {

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM.

METHODS AND RESULTS: Here, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 () gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect.

CONCLUSIONS: Our study demonstrates for the first time that the variants in the gene are associated with HCM, and early detection of the variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of gene variants.

}, issn = {1468-6244}, doi = {10.1136/jmedgenet-2021-107866}, author = {Jain, Pratul Kumar and Jayappa, Shashank and Sairam, Thiagarajan and Mittal, Anupam and Paul, Sayan and Rao, Vinay J and Chittora, Harshil and Kashyap, Deepak K and Palakodeti, Dasaradhi and Thangaraj, Kumarasamy and Shenthar, Jayaprakash and Koranchery, Rakesh and Rajendran, Ranjith and Alireza, Haghighi and Mohanan, Kurukkanparampil Sreedharan and Rathinavel, Andiappan and Dhandapany, Perundurai S} } @article {115013, title = {Richness, not evenness, varies across water availability gradients in grassy biomes on five continents.}, journal = {Oecologia}, volume = {199}, year = {2022}, month = {2022 Jul}, pages = {649-659}, abstract = {

We sought to understand the role that water availability (expressed as an aridity index) plays in determining regional and global patterns of richness and evenness, and in turn how these water availability-diversity relationships may result in different richness-evenness relationships at regional and global scales. We examined relationships between water availability, richness and evenness for eight grassy biomes spanning broad water availability gradients on five continents. Our study found that relationships between richness and water availability switched from positive for drier (South Africa, Tibet and USA) vs. negative for wetter (India) biomes, though were not significant for the remaining biomes. In contrast, only the India biome showed a significant relationship between water availability and evenness, which was negative. Globally, the richness-water availability relationship was hump-shaped, however, not significant for evenness. At the regional scale, a positive richness-evenness relationship was found for grassy biomes in India and Inner Mongolia, China. In contrast, this relationship was weakly concave-up globally. These results suggest that different, independent factors are determining patterns of species richness and evenness in grassy biomes, resulting in differing richness-evenness relationships at regional and global scales. As a consequence, richness and evenness may respond very differently across spatial gradients to anthropogenic changes, such as climate change.

}, keywords = {Biodiversity, China, Ecosystem, Poaceae, Water}, issn = {1432-1939}, doi = {10.1007/s00442-022-05208-6}, author = {Smith, Melinda D and Koerner, Sally E and Avolio, Meghan L and Komatsu, Kimberly J and Eby, Stephanie and Forrestel, Elisabeth J and Collins, Scott L and Wilcox, Kevin R and Ahumada, Rodrigo and Morgan, John W and Oliva, Gabriel and O{\~n}atibia, Gast{\'o}n R and Overbeck, Gerhard E and Peter, Guadalupe and Quiroga, Emiliano and Sankaran, Mahesh and Wu, Jianshuang and Yahdjian, Laura and Yu, Qiang} } @article {108404, title = {Riluzole prevents stress-induced spine plasticity in the hippocampus but mimics it in the amygdala.}, journal = {Neurobiol Stress}, volume = {18}, year = {2022}, month = {2022 May}, pages = {100442}, abstract = {

Stress elicits divergent patterns of structural plasticity in the amygdala and hippocampus. Despite these contrasting effects, at least one of the immediate consequences of stress - elevated levels of extracellular glutamate - is similar in both brain areas. This raises the possibility that the contrasting effects of stress on neuronal plasticity is shaped by differences in astrocytic glutamate clearance in these two brain areas. Although astrocytes play a key role in glutamate reuptake, past analyses of, and interventions against, stress-induced plasticity have focused largely on neurons. Hence, we tested the impact of riluzole, which potentiates glutamate clearance by astrocytic glutamate transporters, on principal neurons and astrocytes in the basal amygdala (BA) and hippocampal area CA1. Chronic immobilization stress reduced spine-density on CA1 pyramidal neurons of male rats. Riluzole, administered in the drinking water during chronic stress, prevented this decrease; but, the drug by itself had no effect. In contrast, the same chronic stress enhanced spine-density on BA principal neurons, and this effect, unlike area CA1, was not reversed by riluzole. Strikingly, riluzole treatment alone also caused spinogenesis in the BA. Thus, the same riluzole treatment that prevented the effect of stress on spines in the hippocampus, mimicked its effect in the amygdala. Further, chronic stress and riluzole alone decreased the neuropil volume occupied by astrocytes in both the BA and CA1 area. Riluzole treatment in stressed animals, however, did not reverse or further add to this reduction in either region. Thus, while the effects on astrocytes were similar, neuronal changes were distinct between the two areas following stress, riluzole and the two together. Therefore, similar to the impact of repeated stress, pharmacological potentiation of glutamate clearance, with or without stress, also leads to differential effects on dendritic spines in principal neurons of the amygdala and hippocampus. This highlights differences in the astrocytic glutamate reuptake machinery that are likely to have important functional consequences for stress-induced dysfunction, and its reversal, in two brain areas implicated in stress-related psychiatric disorders.

}, issn = {2352-2895}, doi = {10.1016/j.ynstr.2022.100442}, author = {Naskar, Saptarnab and Datta, Siddhartha and Chattarji, Sumantra} } @article {111037, title = {The role of sigma factor competition in bacterial adaptation under prolonged starvation.}, journal = {Microbiology (Reading)}, volume = {168}, year = {2022}, month = {2022 May}, abstract = {

The study of adaptive microbial evolution in the laboratory can illuminate the genetic mechanisms of gaining fitness under a pre-defined set of selection factors. Laboratory evolution of bacteria under long-term starvation has gained importance in recent years because of its ability to uncover adaptive strategies that overcome prolonged nutrient limitation, a condition often encountered by natural microbes. In this evolutionary paradigm, bacteria are maintained in an energy-restricted environment in a growth phase called long-term stationary phase (LTSP). This phase is characterized by a stable, viable population size and highly dynamic genetic changes. Multiple independent iterations of LTSP evolution experiments have given rise to mutants that are slow-growing compared to the ancestor. Although the antagonistic regulation between rapid growth and the stress response is well-known in bacteria (especially ), the growth deficit of many LTSP-adapted mutants has not been explored in detail. In this review, I pinpoint the trade-off between growth and stress response as a dominant driver of evolutionary strategies under prolonged starvation. Focusing on mainly -based research, I discuss the various affectors and regulators of the competition between sigma factors to occupy their targets on the genome, and assess its effect on growth advantage in stationary phase (GASP). Finally, I comment on some crucial issues that hinder the progress of the field, including identification of novel metabolites in nutrient-depleted media, and the importance of using multidisciplinary research to resolve them.

}, issn = {1465-2080}, doi = {10.1099/mic.0.001195}, author = {Nandy, Pabitra} } @article {109679, title = {The same stress elicits different effects on anxiety-like behavior in rat models of Fmr1 and Pten.}, journal = {Behav Brain Res}, year = {2022}, month = {2022 Apr 15}, pages = {113892}, abstract = {

Individuals affected by autism spectrum disorders (ASDs) exhibit affective symptoms such as enhanced anxiety, which has been seen in rodent models of ASDs as well. Exposure to stress is also known to be anxiogenic. However, the effects of stress on animal models of ASDs remains less explored. Hence, in the present study we examined the impact of acute foot shock stress on anxiety-like behavior in two monogenic rat models of ASDs, fragile X mental retardation 1 knockout (Fmr1) and phosphatase and tensin homolog heterozygous (Pten). Before exposure to stress, the basal levels of anxiety-like behavior in both Fmr1 and Pten rats were comparable to that seen in wild-type (WT) control rats in an open-field arena. After exposure to the foot shock stress, however, Fmr1 rats showed the highest levels of anxiety-like behavior. WT animals also showed enhanced anxiety-like behavior but not as robustly as the Fmr1 animals. In Pten animals, on the other hand, the same stressor did not elicit any anxiogenic effects. In a separate group of rats, the efficacy of the acute foot shock in triggering a stress response was confirmed wherein a comparable surge in circulating corticosterone was seen in all three experimental groups. Thus, the same acute stress led to different effects on anxiety-like behavior in different rodent models of ASDs, suggesting that vulnerability to stress-induced changes in anxiety may vary with the underlying genetic mutations.

}, issn = {1872-7549}, doi = {10.1016/j.bbr.2022.113892}, author = {Dey, Rohit and Chattarji, Sumantra} } @article {120171, title = {Sample size requirement for achieving multisite harmonization using structural brain MRI features.}, journal = {Neuroimage}, year = {2022}, month = {2022 Nov 23}, pages = {119768}, abstract = {

When data is pooled across multiple sites, the extracted features are confounded by site effects. Harmonization methods attempt to correct these site effects while preserving the biological variability within the features. However, little is known about the sample size requirement for effectively learning the harmonization parameters and their relationship with the increasing number of sites. In this study, we performed experiments to find the minimum sample size required to achieve multisite harmonization (using neuroHarmonize) using volumetric and surface features by leveraging the concept of learning curves. Our first two experiments show that site-effects are effectively removed in a univariate and multivariate manner; however, it is essential to regress the effect of covariates from the harmonized data additionally. Our following two experiments with actual and simulated data showed that the minimum sample size required for achieving harmonization grows with the increasing average Mahalanobis distances between the sites and their reference distribution. We conclude by positing a general framework to understand the site effects using the Mahalanobis distance. Further, we provide insights on the various factors in a cross-validation design to achieve optimal inter-site harmonization.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2022.119768}, author = {Parekh, Pravesh and Bhalerao, Gaurav Vivek and John, John P and Venkatasubramanian, G} } @article {123121, title = {Seasonal dynamics and polyphenism of butterfly communities in the coastal plains of central Western Ghats, India }, journal = {Journal of Biosciences volume}, volume = {47}, year = {2022}, month = {12/2022}, pages = {79}, abstract = {

Long-term socioeconomic progress requires a healthy environment/ecosystem, but anthropogenic activities cause environmental degradation and biodiversity loss. Constant ecological monitoring is, therefore, necessary to assess the state of biodiversity and ecological health. However, baseline data are lacking even for ecologically sensitive regions such as the Western Ghats. We looked at the seasonality and polyphenism of butterflies of the central Western Ghats to obtain baseline population patterns on these charismatic taxa. We recorded 43118 individuals (175 species) using fortnightly time-constrained counts for two consecutive years and found the peak abundance (49\% of the total individuals) in the post-monsoon period (October to January). Seasonal abundance was correlated with the overall increase in species richness. Habitat differences were stronger than seasonality as samples clustered based on sites. Several species also displayed polyphenism with distinct distributions of wet and dry season forms. Seasonal equitability and indicator species analysis showed distinct inter-species differences in seasonality patterns. This work provides key baseline data on the seasonal dynamics of butterflies of the Western Ghats in the context of climate change and conservation. It will help monitor this ecologically sensitive region using butterflies.

}, doi = {doi.org/10.1007/s12038-022-00316-0}, author = {Naik, D. and Rao, R.S.P. and Kunte, K. and Mustak, Mohammed S.} } @article {105163, title = {Selection bias in mutation accumulation.}, journal = {Evolution}, year = {2022}, month = {2022 Jan 06}, abstract = {

Mutation accumulation (MA) experiments, in which de novo mutations are sampled and subsequently characterized, are an essential tool in understanding the processes underlying evolution. In microbial populations, MA protocols typically involve a period of population growth between severe bottlenecks, such that a single individual can form a visible colony. While it has long been appreciated that the action of positive selection during this growth phase cannot be eliminated, it is typically assumed to be negligible. Here, we quantify the effect of both positive and negative selection in MA studies, demonstrating that selective effects can substantially bias the distribution of fitness effects (DFE) and mutation rates estimated from typical MA protocols in microbes. We then present a simple correction for this bias which applies to both beneficial and deleterious mutations, and can be used to correct the observed DFE in multiple environments. We use simulated MA experiments to illustrate the extent to which the MA-inferred DFE differs from the underlying true DFE, and demonstrate that the proposed correction accurately reconstructs the true DFE over a wide range of scenarios; we also provide an example of these corrections applied to experimental data. These results highlight that positive selection during microbial MA experiments is in fact not negligible, but can be corrected to gain a more accurate understanding of fundamental evolutionary\ parameters. This article is protected by copyright. All rights reserved.

}, issn = {1558-5646}, doi = {10.1111/evo.14430}, author = {Wahl, Lindi M and Agashe, Deepa} } @article {108052, title = {Septins tune lipid kinase activity and PI(4,5)P turnover during G-protein-coupled PLC signalling in vivo.}, journal = {Life Sci Alliance}, volume = {5}, year = {2022}, month = {2022 Jun}, abstract = {

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] hydrolysis by phospholipase C (PLC) is a conserved mechanism of signalling. Given the low abundance of PI(4,5)P, its hydrolysis needs to be coupled to resynthesis to ensure continued PLC activity; however, the mechanism by which depletion is coupled to resynthesis remains unknown. PI(4,5)P synthesis is catalyzed by the phosphorylation of phosphatidylinositol 4 phosphate (PI4P) by phosphatidylinositol 4 phosphate 5 kinase (PIP5K). In photoreceptors, photon absorption is transduced into PLC activity and during this process, PI(4,5)P is resynthesized by a PIP5K. However, the mechanism by which PIP5K activity is coupled to PI(4,5)P hydrolysis is unknown. In this study, we identify a unique isoform dPIP5K, that is both necessary and sufficient to mediate PI(4,5)P synthesis during phototransduction. Depletion of PNUT, a non-redundant subunit of the septin family, enhances dPIP5K activity in vitro and PI(4,5)P resynthesis in vivo; co-depletion of dPIP5K reverses the enhanced rate of PI(4,5)P resynthesis in vivo. Thus, our work defines a septin-mediated mechanism through which PIP5K activity is coupled to PLC-mediated PI(4,5)P hydrolysis.

}, issn = {2575-1077}, doi = {10.26508/lsa.202101293}, author = {Kumari, Aastha and Ghosh, Avishek and Kolay, Sourav and Raghu, Padinjat} } @article {109935, title = {A Simple Microfluidic Chip for Long-Term Growth and Imaging of Caenorhabditis elegans.}, journal = {J Vis Exp}, year = {2022}, month = {2022 Apr 11}, abstract = {

Caenorhabditis elegans (C. elegans) have proved to be a valuable model system for studying developmental and cell biological processes. Understanding these biological processes often requires long-term and repeated imaging of the same animal. Long recovery times associated with conventional immobilization methods done on agar pads have detrimental effects on animal health making it inappropriate to repeatedly image the same animal over long periods of time. This paper describes a microfluidic chip design, fabrication method, on-chip C. elegans culturing protocol, and three examples of long-term imaging to study developmental processes in individual animals. The chip, fabricated with polydimethylsiloxane and bonded on a cover glass, immobilizes animals on a glass substrate using an elastomeric membrane that is deflected using nitrogen gas. Complete immobilization of C. elegans enables robust time-lapse imaging of cellular and sub-cellular events in an anesthetic-free manner. A channel geometry with a large cross-section allows the animal to move freely within two partially sealed isolation membranes permitting growth in the channel with a continuous food supply. Using this simple chip, imaging of developmental phenomena such as neuronal process growth, vulval development, and dendritic arborization in the PVD sensory neurons, as the animal grows inside the channel, can be performed. The long-term growth and imaging chip operates with a single pressure line, no external valves, inexpensive fluidic consumables, and utilizes standard worm handling protocols that can easily be adapted by other laboratories using C. elegans.

}, keywords = {Animals, Biological Phenomena, Caenorhabditis elegans, Diagnostic Imaging, Microfluidics}, issn = {1940-087X}, doi = {10.3791/63136}, author = {Dubey, Jyoti and Mondal, Sudip and Koushika, Sandhya P} } @article {113529, title = {Small mammals reduce distance dependence and increase seed predation risk in tropical rainforest fragments}, journal = {BIOTROPICA}, year = {2022}, month = {06/2022}, abstract = {

Seed predation and reduced predation risk with distance from conspecific trees are important influences on tree regeneration in tropical forests. Shifts in animal communities, such as an increase in rodents and other small mammals due to forest fragmentation, could alter patterns of seed predation and affect tree regeneration and community dynamics in forest fragments. We performed a field experiment on four native rainforest tree species in the Western Ghats, India, to test whether fragmentation increases seed predation by mammals and alters the distance dependence of seed predation. We monitored seed predation within open and mammal exclosure plots, near and far from the canopies of conspecific trees, in contiguous and fragmented forests. Seed predation of Cullenia exarillata, Ormosia travancorica, and Syzygium rubicundum was markedly higher in forest fragments, and more so within open plots than exclosures, while the predominantly insect-predated Acronychia pedunculata experienced similar predation in contiguous forests and fragments. Seed predation of C. exarillata and S. rubicundum was unrelated to distance from conspecific trees in open plots in both contiguous forests and fragments, in contrast to exclosures that showed marked near versus far differences in seed predation. Our findings suggest that by increasing overall seed predation risk and imposing similar seed predation risk near and far from adults variably across the tree species, small mammals could alter processes that shape tree diversity and species composition in fragmented tropical rainforests.

}, doi = {10.1111/btp.13137}, author = {Krishnan, Aparna and Osuri, Anand M and Krishnadas, Meghna} } @article {119609, title = {Small-amplitude head oscillations result from a multimodal head stabilization reflex in hawkmoths.}, journal = {Biol Lett}, volume = {18}, year = {2022}, month = {2022 Nov}, pages = {20220199}, abstract = {

In flying insects, head stabilization is an essential reflex that helps to reduce motion blur during fast aerial manoeuvres. This reflex is multimodal and requires the integration of visual and antennal mechanosensory feedback in hawkmoths, each operating as a negative-feedback-control loop. As in any negative-feedback system, the head stabilization system possesses inherent oscillatory dynamics that depend on the rate at which the sensorimotor components of the reflex operate. Consistent with this expectation, we\ observed small-amplitude oscillations in the head motion (or head wobble) of the oleander hawkmoth, which are accentuated when sensory feedback is aberrant. Here, we show that these oscillations emerge from the inherent dynamics of the multimodal reflex underlying gaze stabilization, and that the amplitude of head wobble is a function of both the visual feedback and antennal mechanosensory feedback from the Johnston{\textquoteright}s organs. Our data support the hypothesis that head wobble results from a multimodal, dynamically stabilized reflex loop that mediates head positioning.

}, keywords = {Animals, Arthropod Antennae, Flight, Animal, Head, Manduca, Moths, Reflex}, issn = {1744-957X}, doi = {10.1098/rsbl.2022.0199}, author = {Chatterjee, Payel and Mohan, Umesh and Sane, Sanjay P} } @article {119608, title = {SMC protein RecN drives RecA filament translocation for in~vivo homology search.}, journal = {Proc Natl Acad Sci U S A}, volume = {119}, year = {2022}, month = {2022 Nov 15}, pages = {e2209304119}, abstract = {

While the molecular repertoire of the homologous recombination pathways is well studied, the search mechanism that enables recombination between distant homologous regions is poorly understood. Earlier work suggests that the recombinase RecA, an essential component for homology search, forms an elongated filament, nucleating at the break site. How this RecA structure carries out long-distance search remains unclear. Here, we follow the dynamics of RecA after induction of a single double-strand break on the chromosome. We find that the RecA-nucleoprotein filament, once formed, rapidly translocates in a directional manner in the cell, undergoing several pole-to-pole traversals, until homology search is complete. Concomitant with translocation, we observe dynamic variation in the length of the filament. Importantly in\ vivo, the RecA filament alone is incapable of such long-distance movement; both translocation and associated length variations are contingent on action of structural maintenance of chromosome (SMC)-like protein RecN, via its ATPase cycle. In summary, we have uncovered the three key elements of homology search driven by RecN: mobility of a finite segment of RecA, changes in filament length, and ability to conduct multiple pole-to-pole traversals, which together point to an optimal search strategy.

}, keywords = {Bacterial Proteins, Chromosomes, DNA, Single-Stranded, DNA-Binding Proteins, Rec A Recombinases}, issn = {1091-6490}, doi = {10.1073/pnas.2209304119}, author = {Chimthanawala, Afroze and Parmar, Jyotsana J and Kumar, Sujan and Iyer, Krishnan S and Rao, Madan and Badrinarayanan, Anjana} } @article {117968, title = {Smed-ETS-1 regulates cathepsin+ cell function and epidermal lineage landscape via basement membrane remodeling.}, journal = {J Cell Sci}, year = {2022}, month = {2022 Sep 29}, abstract = {

Extracellular matrix (ECM) is an important component of stem cell niche. Remodelling of ECM mediated by ECM regulators such as MMPs plays a vital role in stem cell function. However, the mechanisms that modulate the function of ECM regulators in the stem cell niche are understudied. Here, we explored the role of the transcription factor (TF), ETS-1 expressed in the cathepsin+ cell population in regulating the expression of the ECM regulator, mt-mmpA, thereby modulating basement membrane thickness. In planarians, the basement membrane around the gut/inner parenchyma is thought to act as a niche for pluripotent stem cells. It has been shown that the early epidermal progenitors migrate outward from this region and progressively differentiate to maintain the terminal epidermis. Our data shows thickening of basement membrane in the absence of ets-1 results in defective migration of stem cells progeny. Furthermore, the absence of ets-1 led to a defective epidermal progenitor landscape, in spite of its lack of expression in those cell types. Together, our results demonstrate the active role of ECM remodelling in regulating tissue homeostasis and regeneration in planaria.

}, issn = {1477-9137}, doi = {10.1242/jcs.259900}, author = {Dubey, Vinay Kumar and Sarkar, Souradeep R and Lakshmanan, Vairavan and Dalmeida, Rimple and Gulyani, Akash and Palakodeti, Dasaradhi} } @article {117964, title = {Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.}, journal = {Cell Rep}, volume = {40}, year = {2022}, month = {2022 Sep 20}, pages = {111390}, abstract = {

Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes. Snail-expressing cells secrete the matricellular protein Mindin, which functions in an autocrine fashion to activate a Src-STAT3 pathway to reinforce their stem/progenitor phenotype. This pathway is activated by the engagement of Mindin with the leukocyte-specific integrin, CD11b (ITGAM), which is also unexpectedly expressed by epidermal keratinocytes. Interestingly, disruption of this signaling module in human cSCC attenuates tumorigenesis, suggesting that targeting Mindin would be a promising therapeutic approach to hinder cancer recurrence.

}, keywords = {Carcinoma, Squamous Cell, Cell Line, Tumor, Epithelial Cells, Extracellular Matrix Proteins, Humans, Integrins, Neoplasm Proteins, Neoplasm Recurrence, Local, Neoplastic Stem Cells, Skin Neoplasms, Snail Family Transcription Factors}, issn = {2211-1247}, doi = {10.1016/j.celrep.2022.111390}, author = {Badarinath, Krithika and Dam, Binita and Kataria, Sunny and Zirmire, Ravindra K and Dey, Rakesh and Kansagara, Gaurav and Ajnabi, Johan and Hegde, Akshay and Singh, Randhir and Masudi, Tafheem and Sambath, Janani and Sachithanandan, Sasikala P and Kumar, Prashant and Gulyani, Akash and He, You-Wen and Krishna, Sudhir and Jamora, Colin} } @article {112958, title = {Spatial decoupling of ? and ? diversity suggest different management needs for coral reef fish along an extensive mid-oceanic ridge}, journal = {GLOBAL ECOLOGY AND CONSERVATION}, volume = {36}, year = {2022}, month = {08/2022}, abstract = {

Understanding the underlying drivers of biodiversity is essential for conservation planning of large, connected seascapes. We tested how patterns in alpha and beta components of species and functional diversity of coral reef fish (214, species, 23 families) varied along the extensive Chagos Lakshadweep oceanic ridge (the largest chain of mid-oceanic atolls in the Indian Ocean) and evaluated geomorphological, environmental, and anthropogenic predictors of diversity patterns. alpha and beta diversity (species and functional) showed contrasting patterns along the ridge; richness and alpha diversity decreased towards the north and were influenced by anthropogenic pressures, while beta diversity increased towards the north, along environmental gradients and with geographic distance. Species beta diversity was dominated by turnover (\> 80\%), while functional beta diversity was dominated by nestedness (\> 60\%). Geographically distant reefs (\> 2000 km apart) with high structural complexity were functionally similar, illustrating a ridge-wide capacity for reefs to maintain ecological structure and function despite significant differences in biodiversity. Low spatial congruence in different facets of biodiversity suggest differentiated management needs for reef fish communities along the Chagos-Lakshadweep ridge. Specifically, while a single large marine reserve may be effective for biodiversity conservation in the Chagos archipelago in the south, a network of several smaller conservation areas may be needed to confer resilience to densely populated and biologically differentiated reefs further north.

}, doi = {10.1016/j.gecco.2022.e02110}, author = {Karkarey, Rucha and Arthur, Rohan and Nash, Kirsty L. and Pratchett, Morgan S. and Sankaran, Mahesh and Graham, Nicholas A. J.} } @article {107012, title = {Store-operated Ca2+ entry regulates neuronal gene expression and function.}, journal = {Curr Opin Neurobiol}, volume = {73}, year = {2022}, month = {02/2022}, pages = {102520}, abstract = {

Recent studies with mutants of STIM and Orai have identified store-operated Ca2+ entry as an important regulator of neuronal function in Drosophila and mouse. Cellular Ca2+ imaging and electrophysiological studies demonstrate changes in ion channel function in neurons with loss of store-operated Ca2+ entry. Importantly, such changes are specific to neuronal subtypes. Transcriptomic and single-cell gene expression studies from the mouse brain identified wide, and isoform-specific differences, in expression of genes required for ER-store Ca2+ release and store-operated Ca2+ entry, across different neuronal classes. Loss of store-operated Ca2+ entry in neurons impacts neuronal gene expression profiles and includes genes encoding ion channels. The functional significance of store-operated Ca2+ entry across specific neuronal subtypes and in the context of neurodegenerative syndromes needs further study.

}, doi = {10.1016/j.conb.2022.01.005}, author = {Mitra, Rishav and Hasan, Gaiti} } @article {111038, title = {Stress Elicits Contrasting Effects on Rac1-Cofilin Signaling in the Hippocampus and Amygdala.}, journal = {Front Mol Neurosci}, volume = {15}, year = {2022}, month = {2022}, pages = {880382}, abstract = {

There is accumulating evidence for contrasting patterns of stress-induced morphological and physiological plasticity in glutamatergic synapses of the hippocampus and amygdala. The same chronic stress that leads to the formation of dendritic spines in the basolateral amygdala (BLA) of rats, leads to a loss of spines in the hippocampus. However, the molecular underpinnings of these divergent effects of stress on dendritic spines are not well understood. Since the activity of the Rho GTPase Rac1 and the actin-depolymerizing factor cofilin are known to play a pivotal role in spine morphogenesis, we investigated if alterations in this signaling pathway reflect the differential effects of stress on spine plasticity in the hippocampus and amygdala. A day after the end of chronic immobilization stress (2 h/day for 10 days), we found a reduction in the activity of Rac1, as well as its effector p21-activated kinase 1 (PAK1), in the rat hippocampus. These changes, in turn, decreased cofilin phosphorylation alongside a reduction in the levels of profilin isoforms. In striking contrast, the same chronic stress increased Rac1, PAK1 activity, cofilin phosphorylation, and profilin levels in the BLA, which is consistent with enhanced actin polymerization leading to spinogenesis in the BLA. In the hippocampus, on the other hand, the same stress caused the opposite changes, the functional consequences of which would be actin depolymerization leading to the elimination of spines. Together, these findings reveal a role for brain-region specific differences in the dysregulation of Rac1-to-cofilin signaling in the effects of repeated stress on two brain areas that are implicated in the emotional and cognitive symptoms of stress-related psychiatric disorders.

}, issn = {1662-5099}, doi = {10.3389/fnmol.2022.880382}, author = {Bose, Mihika and Nawaz, Mohammad Sarfaraz and Pal, Rakhi and Chattarji, Sumantra} } @article {117965, title = {Structures of distantly-related interacting protein homologues are less divergent than non-interacting homologues.}, journal = {FEBS Open Bio}, year = {2022}, month = {2022 Sep 23}, abstract = {

Homologous proteins can display high structural variation due to evolutionary divergence at low sequence identity. This classical inverse relationship between sequence identity and structural similarity, established many years ago, has remained true between homologous proteins of known structure over time. However, a large number of heteromeric proteins also exist in the structural data bank, where the interacting subunits belong to the same fold and maintain low sequence identity between themselves. It is not clear if there is any selection pressure to deviate from the inverse sequence-structure relationship for such interacting distant homologues, in comparison to pairs of homologues which are not known to interact. We examined 12,824 fold pairs of interacting homologues of known structure, which includes both heteromers and multi-domain proteins. These were compared with monomeric proteins, resulting in 26,082 fold pairs as a dataset of non-interacting homologous systems. Interacting homologues were found to retain higher structural similarity than non-interacting homologues at diminishing sequence identity in a statistically significant manner. Interacting homologues are more similar in their 3D structures than non-interacting homologues and have a preference towards symmetric association. There appears to be a structural constraint between remote homologues due to this commitment.

}, issn = {2211-5463}, doi = {10.1002/2211-5463.13492}, author = {Naveenkumar, Nagarajan and Prabantu, Vasam Manjveekar and Vishwanath, Sneha and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {108401, title = {Supramolecular self-assembly mediated aggregation-induced emission of fluorene-derived cyanostilbenes: multifunctional probes for live cell-imaging.}, journal = {J Mater Chem B}, year = {2022}, month = {2022 Mar 16}, abstract = {

The first discovery of aggregation-induced emission (AIE), whereby luminogen aggregation plays a positive role in enhancing the light-emission efficiency, has piqued the interest of many researchers as it opens up a new avenue for the exploration of practically beneficial luminescent materials. Diverse AIE-active luminogens (or AIEgens) with tunable emission colours and very high quantum yields (up to unity) in the solid state have been extensively utilised in a broad range of fields including optoelectronics, energy and bioscience. In this article, we describe novel fluorene-based fluorogens that exhibit bright emission in the solid-state, mechanical stimuli-responsive optical properties and aggregation-induced emissive ability, and were able to modulate their donor and acceptor properties. The target compounds were synthesized by a Knoevenagel condensation followed by Suzuki cross-coupling reaction, which tends to result in good yields. The target cyanostilbenes (4a-4d) show different reversibly switched states with high contrast through morphology modulation and demonstrate solvatochromic, vapochromic, and AIE properties. These results strongly suggest that compound 4d has better properties than the other derivatives (4a-c) due to the presence of extended donor-acceptor ability. Moreover, density-functional theory (DFT) calculations strongly support the UV-Vis and fluorescence spectral studies. The formation of nano-flakes and cuboid-shaped nanocrystals was further confirmed by FE-SEM and AFM studies. The synthesized compound 4d displayed very bright emission in the solid state and in the aggregate state as compared with the other derivatives (4a-4c). These results might be due to the presence of high-color contrast, which is an advantage for elucidation and overcomes the challenges exhibited in live-cell imaging applications. Moreover, an MTT assay on live A549 cells incubated with the target compound (4d) showed very low cytotoxicity even at high concentrations.

}, issn = {2050-7518}, doi = {10.1039/d1tb02322e}, author = {Gouthaman, Siddan and Jayaraj, Anjitha and Sugunalakshmi, Madurai and Sivaraman, Gandhi and P, Chinna Ayya Swamy} } @article {108060, title = {Synthesizing habitat connectivity analyses of a globally important human-dominated tiger-conservation landscape.}, journal = {Conserv Biol}, year = {2022}, month = {2022 Mar 14}, abstract = {

As ecological data and associated analyses become more widely available, synthesizing results for effective communication with stakeholders is essential. In the case of wildlife corridors, managers in human-dominated landscapes need to identify both the locations of corridors and multiple stakeholders for effective oversight. We synthesized 5 independent studies of tiger (Panthera tigris) connectivity in central India, a global priority landscape for tiger conservation, to quantify agreement on landscape permeability for tiger movement and potential movement pathways. We used the latter analysis to identify connectivity areas on which studies agreed and stakeholders associated with these areas to determine relevant participants in corridor management. Three or more of the 5 studies{\textquoteright} resistance layers agreed in 63\% of the study area. Areas in which all studies agree on resistance were of primarily low (66\%, e.g., forest) and high (24\%, e.g., urban) resistance. Agreement was lower in intermediate resistance areas (e.g., agriculture). Despite these differences, the studies largely agreed on areas with high levels of potential movement: \>40\% of high average (top 20\%) current-flow pixels were also in the top 20\% of current-flow agreement pixels (measured by low variation), indicating consensus connectivity areas (CCAs) as conservation priorities. Roughly 70\% of the CCAs fell within village administrative boundaries, and 100\% overlapped forest department management boundaries, suggesting that people live and use forests within these priority areas. Over 16\% of total CCAs{\textquoteright} area was within 1 km of linear infrastructure (437 road, 170 railway, 179 transmission line, and 339 canal crossings; 105 mines within 1 km of CCAs). In 2019, 78\% of forest land diversions for infrastructure and mining in Madhya Pradesh (which comprises most of the study region) took place in districts with CCAs. Acute competition for land in this landscape with globally important wildlife corridors calls for an effective comanagement strategy involving local communities, forest departments, Appendix 1 and infrastructure planners. This article is protected by copyright. All rights reserved.

}, issn = {1523-1739}, doi = {10.1111/cobi.13909}, author = {Schoen, Jay M and Neelakantan, Amrita and Cushman, Samuel A and Dutta, Trishna and Habib, Bilal and Jhala, Yadvendradev V and Mondal, Indranil and Ramakrishnan, Uma and Reddy, P Anuradha and Saini, Swati and Sharma, Sandeep and Thatte, Prachi and Yumnam, Bibek and DeFries, Ruth} } @article {112957, title = {The thermal niche and phylogenetic assembly of evergreen tree metacommunities in a mid-to-upper tropical montane zone.}, journal = {Proc Biol Sci}, volume = {289}, year = {2022}, month = {2022 Jun 29}, pages = {20220038}, abstract = {

Frost and freezing temperatures have posed an obstacle to tropical woody evergreen plants over evolutionary time scales. Thus, along tropical elevation gradients, frost may influence woody plant community structure by filtering out lowland tropical clades and allowing extra-tropical lineages to establish at higher elevations. Here we assess the extent to which frost and freezing temperatures influence the taxonomic and phylogenetic structure of naturally patchy evergreen forests (locally known as ) along a mid-upper montane elevation gradient in the Western Ghats, India. Specifically, we examine the role of large-scale macroclimate and factors affecting local microclimates, including patch size and distance from edge, in driving metacommunity structure. We find that the metacommunity shows phylogenetic overdispersion with elevation, with greater representation of extra-tropical lineages above 2000 m, and marked turnover in taxonomic composition of woody communities near the frost-affected forest edge above 2000 m, from those below 2000 m. Both minimum winter temperature and patch size were equally important in determining metacommunity structure, with plots inside very large dominated by older tropical lineages, with many endemics. Phylogenetic overdispersion in the upper montane metacommunity thus resulted from tropical lineages persisting in the interiors of large closed frost-free where their regeneration niche has been preserved over time.

}, keywords = {Biological Evolution, Cold Temperature, Fever, Forests, Phylogeny, Wood}, issn = {1471-2954}, doi = {10.1098/rspb.2022.0038}, author = {Das, Arundhati Abin and Ratnam, Jayashree} } @article {109311, title = {Three new and notes on two other jumping spider species of the genus Stenaelurillus Simon, 1886 (Salticidae: Aelurillina) from the Deccan Plateau, India.}, journal = {Zootaxa}, volume = {5125}, year = {2022}, month = {2022 Apr 07}, pages = {1-19}, abstract = {

We describe three new species of Stenaelurillus Simon, 1886 from the Deccan Plateau of India, and report on populations of S. sarojinae Caleb Mathai, 2014 and S. marusiki Logunov, 2001. One of the new species, S. shwetamukhi Marathe, Sanap, Maddison, sp. nov., has black-and-white markings, characteristic of several other Indian Stenaelurillus species. The other two new species, S. tamravarni Marathe Maddison, sp. nov., and S. vyaghri Sanap, Joglekar, Caleb, sp. nov., are colourful and with fringed male abdomens, like several other Indian species including S. sarojinae. The population of S. sarojinae from Mysuru, Karnataka, shows colours distinct from the population at the type locality. The female of S. marusiki is described for the first time.

}, keywords = {Animal Distribution, Animals, Female, India, Male, Spiders}, issn = {1175-5334}, doi = {10.11646/zootaxa.5125.1.1}, author = {Marathe, Kiran and Sanap, Rajesh and Joglekar, Anuradha and Caleb, John T D and Maddison, Wayne P} } @article {108398, title = {Three new cryptic species of South Asian Cnemaspis Strauch, 1887 (Squamata, Gekkonidae) from Karnataka, India}, journal = {VERTEBRATE ZOOLOGY }, volume = {72}, year = {2022}, month = {03/2022}, pages = {115-142}, abstract = {

We describe three new small-bodied, cryptic species of south Asian Cnemaspis belonging to the mysoriensis and goaensis clades from the Mysore Plateau and the Western Ghats biodiversity hotspot in Karnataka, peninsular India; and provide a key to mem-bers of each clade, besides providing the first ND2 sequence data for C. ranganaensis. Cnemaspis tigris sp. nov. from Kaiwara in Karnataka is a member of the mysoriensis clade and can be morphologically distinguished from all six described members of the clade in a number of meristic characters and subtle differences in colouration, beside \>= 12.1-23.4 \% uncorrected pairwise ND2 sequence divergence. Cnemaspis sakleshpurensis sp. nov. from Sakleshpur and C. vijayae sp. nov. from Coorg, both in the Western Ghats of Karnataka, are members of the goaensis clade and are easily diagnosed from all three described members of the clade in meristic characters beside 5.2-14.8 \% divergence from described members of the clade and 14.6 \% from each other in uncorrected pairwise ND2 sequence divergence. The discovery of these new species from two different clades and biogeographic regions is not surprising, given the steep rise in the number of species of Cnemaspis known from peninsular India. Comprehensive geographic sampling in conjunction with molecular and morphological data is essential to understand the true diversity and distributional ranges of species within this ancient clade of gekkonid lizards.

}, doi = {10.3897/vz.72.e76308}, author = {Khandekar, Akshay and Thackeray, Tejas and Agarwal, Ishan} } @article {115008, title = {To a charismatic rescue: Designing a blueprint to steer Fishing Cat conservation for safeguarding Indian wetlands}, journal = {JOURNAL FOR NATURE CONSERVATION}, volume = {68}, year = {2022}, month = {07/2022}, abstract = {

Wetland conservation in the Indo-tropics can benefit from the protection of the charismatic Fishing Cat. India, supporting ~ 40\% of its known range, is a stronghold for the species. Here, using multiple information sources we outline a framework to safeguard fishing cats in India. Specifically, we a) estimated district-level Conservation priority scores (using presence records, and habitat suitability and habitat connectivity) to identify ecologically important habitats, b) estimated state-level Conservation likelihood scores assessing the success potential of any conservation intervention, c) collated district-level Conservation initiative information identifying ongoing efforts for species and/or habitat conservation. We consecutively assessed the spatial congruence between (a), (b) and (c) to delineate species{\textquoteright} conservation areas and corresponding action goals (blueprint). Using information on habitat suitability, we also delineated survey landscapes. Although Fishing Cat records were found in 12 Indian states, only a small proportion of the state area was identified harbouring optimal habitat for the species. Three broad habitat clusters Terai arc, Eastern coast, and Brahmaputra floodplains were identified, with overall high habitat connectivity. Most districts ranking high in Conservation priority scored low in Conservation likelihood. Districts with Fishing Cat presence (n = 60) were delineated into four tiers of action landscapes and the majority of districts classified as survey landscapes (n = 156) were found in the Terai arc. We use our results to recommend and discuss conservation actions for districts identified in our blueprint. Flagship species conservation approach has substantial potential to enrich wetland conservation, for which our blueprint can act as a baseline.

}, doi = {10.1016/j.jnc.2022.126225}, author = {Rana, Divyashree and Samad, Imran and Rastogi, Sankarshan} } @article {117967, title = {Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms.}, journal = {Front Cell Dev Biol}, volume = {10}, year = {2022}, month = {2022}, pages = {948351}, abstract = {

9p21 locus is one of the most reproducible regions in genome-wide association studies (GWAS). The region harbors genes that code for p16, p15, and p14 proteins, and it also harbors a long gene desert adjacent to these genes. The polymorphisms that are associated with several diseases and cancers are present in these genes and the gene desert region. These proteins are critical cell cycle regulators whose transcriptional dysregulation is strongly linked with cellular regeneration, stemness, aging, and cancers. Given the importance of this locus, intense scientific efforts on understanding the regulation of these genes via promoter-driven mechanisms and recently, via the distal regulatory mechanism have provided major insights. In this review, we describe these mechanisms and propose the ways by which this locus can be targeted in pathologies and aging.

}, issn = {2296-634X}, doi = {10.3389/fcell.2022.948351}, author = {Farooq, Umer and Notani, Dimple} } @article {105161, title = {The Transcriptional Response to Oxidative Stress is Independent of Stress-Granule Formation.}, journal = {Mol Biol Cell}, year = {2022}, month = {2022 Jan 05}, pages = {mbcE21080418}, abstract = {

Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this, we characterized transcriptional changes in S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Oxidative stress for 3-hours predominantly resulted in induction or upregulation of stress-responsive mRNAs whose levels peaked during recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for chaperones, including HSP70s, small heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced cytoplasmic SGs that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/Rasputin protein inhibited SG assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced gene expression alterations appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

}, issn = {1939-4586}, doi = {10.1091/mbc.E21-08-0418}, author = {Singh, Amanjot and Kandi, Arvind Reddy and Jayaprakashappa, Deepa and Thuery, Guillaume and Purohit, Devam J and Huelsmeier, Joern and Singh, Rashi and Pothapragada, Sai Shruti and Ramaswami, Mani and Bakthavachalu, Baskar} } @article {121148, title = {Transcriptome profiling of two Moringa species and insights into their antihyperglycemic activity.}, journal = {BMC Plant Biol}, volume = {22}, year = {2022}, month = {2022 Dec 02}, pages = {561}, abstract = {

BACKGROUND: Moringa concanensis Nimmo (MC), a plant that resembles Moringa oleifera Lam. (MO), has less scientific information but has traditionally been used as a medicinal plant. Moringa species have long been known for their medicinal qualities, which include antioxidant, anti-inflammatory, anticancer, and antihyperglycemic effects. We investigated the antidiabetic potential of MC and MO species in this study by using transcriptome profiling, metabolite analysis, and in vitro assay studies.

RESULTS: Our transcriptome analysis revealed the expression of enzymes involved in the biosynthesis of quercetin, chlorogenic acid, and benzylamine, all of which have previously been shown to have antidiabetic activity. We compared the expression patterns of five different tissues from MC and MO and it was found that the key enzymes involved in the biosynthesis of these compounds were highly expressed in leaf tissue. The expression estimated by MC transcriptome data in different tissues was verified using RT-qPCR analysis. The amount of these compounds was further quantified in the crude leaf extract of both species and found that MC had a higher abundance of quercetin and chlorogenic acid than MO. The crude leaf extract from both MC and MO were further tested in vitro, and the results demonstrated strong inhibitory activity for α-glucosidase and DPP-IV enzymes. Our findings suggest that compounds in leaf tissue, such as quercetin, benzylamine, and chlorogenic acid, could play a significant role in this antidiabetic activity. In addition, when comparing MO plants, we found that MC had a slightly higher effect in expression, abundance, and inhibitory activity.

CONCLUSIONS: This study presents the first report of MC transcriptome data, as well as a comparison of its anti-diabetic activity to MO. Our analysis discussed the significance of leaf tissue in antidiabetic activity compared to other tissues of both species. Overall, this study not only provides transcriptome resources for Moringa species, but also sheds light on antidiabetic potential of both species.

}, keywords = {Benzylamines, Chlorogenic Acid, Gene Expression Profiling, Hypoglycemic Agents, Moringa, Plant Extracts, Quercetin}, issn = {1471-2229}, doi = {10.1186/s12870-022-03938-6}, author = {Shafi, K Mohamed and Sajeevan, Radha Sivarajan and Kouser, Sania and Vishnuprasad, Chethala N and Sowdhamini, Ramanathan} } @article {112945, title = {tREPs-A New Class of Functional tRNA-Encoded Peptides.}, journal = {ACS Omega}, volume = {7}, year = {2022}, month = {2022 Jun 07}, pages = {18361-18373}, abstract = {

We asked if transfer RNA (tRNA) ever got an opportunity of translating its own sequence during evolution, what would have been the function of such tRNA-encoded peptides (tREPs)? If not, could one artificially synthesize tREPs to study the corresponding functional outcomes? Here, we report a novel, first-in-the-class, chemically synthesized tREP-18 molecule originating from the tRNA sequence showing potent antileishmanial property. As a first step, tRNAs were computationally translated into peptide sequence equivalents and a database of full-length hypothetical tREPs was created. The tREP sequences were sent into sequence, structure, and energy filters to narrow down potential peptides for experimental validation. Based on the functional predictions, tREPs were screened against antiparasitic targets, leading to the identification of tREP-18 as a potential antiparasitic peptide. The in vitro assay of chemically synthesized tREP-18 on the strain of showed its potent antileishmanial property (IC50 value of 22.13 nM). The atomic force microscopy and scanning electron microscopy images indicated significant alteration in the cytoskeletal architecture of tREP-18-treated parasites. Also, tREP-18 seems to destabilize the mitochondrial membrane potential of parasites, disrupting their cellular integrity and leading to parasitic death. The cellular assays of the tREP-18 peptide on the BS12 strain, a clinical isolate of post-kala azar dermal leishmaniasis, demonstrated its significant efficacy at an IC50 value of 15 nM. The tREP-18 peptide showed a toxic effect on the amastigote stage of the parasite, showing macrophage pathogen clearance at a concentration of 22.5 nM. This study provides the proof of the concept of making a new class of functional peptides from tRNA sequences. It also opens a huge untapped tRNA-peptide space toward novel discoveries and applications. In the future, it would be interesting to perform tREP edits and redesign tREPs toward specific applications.

}, issn = {2470-1343}, doi = {10.1021/acsomega.2c00661}, author = {Chakrabarti, Amrita and Kaushik, Monika and Khan, Juveria and Soota, Deepanshu and Ponnusamy, Kalairasan and Saini, Sunil and Manvati, Siddharth and Singhal, Jhalak and Ranganathan, Anand and Pati, Soumya and Dhar, Pawan Kumar and Singh, Shailja} } @article {105898, title = {Two photon imaging of calcium responses in murine Purkinje neurons.}, journal = {STAR Protoc}, volume = {3}, year = {2022}, month = {2022 Mar 18}, pages = {101105}, abstract = {

Purkinje neurons (PNs) are an important component of the motor learning and coordination circuit and are affected in spino-cerebellar ataxias. Maintaining healthy PNs in cerebellar slices and recording their Ca transients can be challenging. Here, we describe a protocol for measuring Ca transients in PNs from adult mice, including problem-solving tips. This protocol can be used to measure neuronal excitability and agonist-mediated Ca signaling in cerebellar slices expressing a genetic Ca reporter in all PNs, thus improving yield of data. For complete details on the use and execution of this profile, please refer to Dhanya and Hasan (2021).

}, issn = {2666-1667}, doi = {10.1016/j.xpro.2021.101105}, author = {Dhanya, Sreeja Kumari and Hasan, Gaiti} } @article {120170, title = {Understanding the Genome-Wide Transcription Response To Various cAMP Levels in Bacteria Using Phenomenological Models.}, journal = {mSystems}, year = {2022}, month = {2022 Nov 21}, pages = {e0090022}, abstract = {

Attempts to understand gene regulation by global transcription factors have largely been limited to expression studies under binary conditions of presence and absence of the transcription factor. Studies addressing genome-wide transcriptional responses to changing transcription factor concentration at high resolution are lacking. Here, we create a data set containing the entire Escherichia coli transcriptome in Luria-Bertani (LB) broth as it responds to 10 different cAMP concentrations spanning the biological range. We use the Hill{\textquoteright}s model to accurately summarize individual gene responses into three intuitively understandable parameters, , , and , reflecting the sensitivity, nonlinearity, and midpoint of the dynamic range. Our data show that most cAMP-regulated genes have an of \>2, with their values centered around the wild-type concentration of cAMP. Additionally, cAMP receptor protein (CRP) affinity to a promoter is correlated with but not , hinting that a high-affinity CRP promoter need not ensure transcriptional activation at lower cAMP concentrations and instead affects the magnitude of the response. Finally, genes belonging to different functional classes are tuned to have different , , and values. We demonstrate that phenomenological models are a better alternative for studying gene expression trends than classical clustering methods, with the phenomenological constants providing greater insights into how genes are tuned in a regulatory network. Different genes may follow different trends in response to various transcription factor concentrations. In this study, we ask two questions: (i) what are the trends that different genes follow in response to changing transcription factor concentrations and (ii) what methods can be used to extract information from the gene trends so obtained. We demonstrate a method to analyze transcription factor concentration-dependent genome-wide expression data using phenomenological models. Conventional clustering methods and principal-component analysis (PCA) can be used to summarize trends in data but have limited interpretability. The use of phenomenological models greatly enhances the interpretability and thus utility of conventional clustering. Transformation of dose-response data into phenomenological constants opens up avenues to ask and answer many different kinds of question. We show that the phenomenological constants obtained from the model fits can be used to generate insights about network topology and allows integration of other experimental data such as chromatin immunoprecipitation sequencing (ChIP-seq) to understand the system in greater detail.

}, issn = {2379-5077}, doi = {10.1128/msystems.00900-22}, author = {Chakraborty, Shweta and Singh, Parul and Seshasayee, Aswin Sai Narain} } @article {115050, title = {Unjamming and emergent nonreciprocity in active ploughing through a compressible viscoelastic fluid.}, journal = {Nat Commun}, volume = {13}, year = {2022}, month = {2022 Aug 04}, pages = {4533}, abstract = {

A dilute suspension of active Brownian particles in a dense compressible viscoelastic fluid, forms a natural setting to study the emergence of nonreciprocity during a dynamical phase transition. At these densities, the transport of active particles is strongly influenced by the passive medium and shows a dynamical jamming transition as a function of activity and medium density. In the process, the compressible medium is actively churned up - for low activity, the active particle gets self-trapped in a cavity of its own making, while for large activity, the active particle ploughs through the medium, either accompanied by a moving anisotropic wake, or leaving a porous trail. A hydrodynamic approach makes it evident that the active particle generates a long-range density wake which breaks fore-aft symmetry, consistent with the simulations. Accounting for the back-reaction of the compressible medium leads to (i) dynamical jamming of the active particle, and (ii) a dynamical non-reciprocal attraction between two active particles moving along the same direction, with the trailing particle catching up with the leading one in finite time. We emphasize that these nonreciprocal effects appear only when the active particles are moving and so manifest in the vicinity of the jamming-unjamming transition.

}, issn = {2041-1723}, doi = {10.1038/s41467-022-31984-z}, author = {Banerjee, Jyoti Prasad and Mandal, Rituparno and Banerjee, Deb Sankar and Thutupalli, Shashi and Rao, Madan} } @article {116715, title = {Using Environmental Sampling to Enable Zoonotic Pandemic Preparedness.}, journal = {J Indian Inst Sci}, year = {2022}, month = {2022 Sep 07}, pages = {1-20}, abstract = {

The current pandemic caused by the SARS CoV-2, tracing back its origin possibly to a coronavirus associated with bats, has ignited renewed interest in understanding zoonotic spillovers across the globe. While research is more directed towards solving the problem at hand by finding therapeutic strategies and novel vaccine techniques, it is important to address the environmental drivers of pathogen spillover and the complex biotic and abiotic drivers of zoonoses. The availability of cutting-edge genomic technologies has contributed enormously to preempt viral emergence from wildlife. However, there is still a dearth of studies from species-rich South Asian countries, especially from India. In this review, we outline the importance of studying disease dynamics through environmental sampling from wildlife in India and how ecological parameters of both the virus and the host community may play a role in mediating cross-species spillovers. Non-invasive sampling using feces, urine, shed hair, saliva, shed skin, and feathers has been instrumental in providing genetic information for both the host and their associated pathogens. Here, we discuss the advances made in environmental sampling protocols and strategies to generate genetic data from such samples towards the surveillance and characterization of potentially zoonotic pathogens. We primarily focus on bat-borne or small mammal-borne zoonoses and propose a conceptual framework for non-invasive strategies to tackle the threat of emerging zoonotic infections.

}, issn = {0970-4140}, doi = {10.1007/s41745-022-00322-z}, author = {Sanyal, Avirup and Agarwal, Sanskriti and Ramakrishnan, Uma and Garg, Kritika M and Chattopadhyay, Balaji} } @article {106150, title = {Versatile role of miR-24/24-1*/24-2*expression in cancer and other human diseases}, journal = {AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH }, volume = {14}, year = {2022}, month = {01/2022}, pages = {20-54}, abstract = {

MiRNAs (miRs) have been proven to be well-validated therapeutic targets. Emerging evidence has demonstrated that intricate, intrinsic and paradoxical functions of miRs are context-dependent because of their multiple upstream regulators, broad spectrum of downstream molecular targets and distinct expression in various tissues, organs and disease states. Targeted therapy has become an emerging field of research. One key for the development of successful miR-based/targeted therapy is to acquire integrated knowledge of its regulatory network and its association with disease phenotypes to identify critical nodes of the underlying pathogenesis. Herein, we systematically summarized the comprehensive role of miR-24-3p (miR-24), along with its passenger strands miR24-1-5p* (miR-24-1) and miR-24-2-5p* (miR-24-2), emphasizing their microenvironment, intracellular targets, and associated gene networks and regulatory phenotypes in 18 different cancer types and 13 types of other disorders. MiR-24 targets and regulates numerous genes in various cancer types and enhances the expression of several oncogenes (e.g., cMyc, BCL2 and HIF1), which are challenging in terms of druggability. In contrast, several tumor suppressor proteins (p21 and p53) have been reported to be downregulated by miR-24. MiR-24 also regulates the cell cycle and is associated with numerous cancer hallmarks such as apoptosis, proliferation, metastasis, invasion, angiogenesis, autophagy, drug resistance and other diseases pathogenesis. Overall, miR-24 plays an emerging role in the diagnosis, prognosis and pathobiology of various diseases. MiR-24 is a potential target for targeted therapy in the era of precision medicine, which expands the landscape of targetable macromolecules, including undruggable proteins.

}, url = {https://e-century.us/files/ajtr/14/1/ajtr0135181.pdf}, author = {Mukherjee, Sanjukta and Shelar, Bhagyashree and Krishna, Sudhir} } @article {115046, title = {α-Synuclein aggregation intermediates form fibril polymorphs with distinct prion-like properties.}, journal = {J Mol Biol}, year = {2022}, month = {2022 Jul 27}, pages = {167761}, abstract = {

α-Synuclein (α-Syn) amyloids in synucleinopathies are suggested to be structurally and functionally diverse, reminiscent of prion-like strains. But how the aggregation of the same precursor protein results in the formation of fibril polymorphs remains elusive. Here, we demonstrate the structure-function relationship of two polymorphs, pre-matured fibrils (PMFs) and helix-matured fibrils (HMFs), based on α-Syn aggregation intermediates. These polymorphs display the structural differences as demonstrated by solid-state NMR and mass spectrometry studies and also possess different cellular activities such as seeding, internalization, and cell-to-cell transfer of aggregates. HMFs with a compact core structure exhibit low seeding potency but readily internalize and transfer from one cell to another. The less structured PMFs lack transcellular transfer ability but induce abundant α-Syn pathology and trigger the formation of aggresomes in cells. Overall, the study highlights that the conformational heterogeneity in the aggregation pathway may lead to fibril polymorphs with distinct prion-like behavior.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2022.167761}, author = {Mehra, Surabhi and Ahlawat, Sahil and Kumar, Harish and Datta, Debalina and Navalkar, Ambuja and Singh, Nitu and Patel, Komal and Gadhe, Laxmikant and Kadu, Pradeep and Kumar, Rakesh and Jha, Narendra N and Sakunthala, Arunima and Sawner, Ajay S and Padinhateeri, Ranjith and Udgaonkar, Jayant B and Agarwal, Vipin and Maji, Samir K} } @article {94535, title = {1-Undecene from Pseudomonas aeruginosa is an olfactory signal for flight-or-fight response in Caenorhabditis elegans.}, journal = {EMBO J}, year = {2021}, month = {2021 Jun 04}, pages = {e106938}, abstract = {

Animals possess conserved mechanisms to detect pathogens and to improve survival in their presence by altering their own behavior and physiology. Here, we utilize Caenorhabditis elegans as a model host to ask whether bacterial volatiles constitute microbe-associated molecular patterns. Using gas chromatography-mass spectrometry, we identify six prominent volatiles released by the bacterium Pseudomonas aeruginosa. We show that a specific volatile, 1-undecene, activates nematode odor sensory neurons inducing both flight and fight responses in worms. Using behavioral assays, we show that worms are repelled by 1-undecene and that this aversion response is driven by the detection of this volatile through AWB odor sensory neurons. Furthermore, we find that 1-undecene odor can induce immune effectors specific to P. aeruginosa via AWB neurons and that brief pre-exposure of worms to the odor enhances their survival upon subsequent bacterial infection. These results show that 1-undecene derived from P. aeruginosa serves as a pathogen-associated molecular pattern for the induction of protective responses in C. elegans.

}, issn = {1460-2075}, doi = {10.15252/embj.2020106938}, author = {Prakash, Deep and Ms, Akhil and Radhika, Buddidhathi and Venkatesan, Radhika and Chalasani, Sreekanth H and Singh, Varsha} } @article {88612, title = {Adaptive tuning of the exploitation-exploration trade-off in four honey bee species}, journal = {Behavioral Ecology and Sociobiology}, volume = {75}, year = {2021}, month = {01/2021}, abstract = {

Foraging animals continually face the decision of whether to exploit known resources or explore for new ones, a decision with large implications for their fitness. Though animal foraging decisions have been extensively studied, we currently lack a deep understanding of how the exploitation-exploration trade-off has evolved, including how it is shaped by divergent selection pressures between species. As a first step towards examining how the exploitation-exploration trade-off has been adaptively tuned by natural selection, we compared the exploratory behavior of four honey bee species that differ in traits such as nest architecture, body size, and colony size. In a common behavioral context{\textemdash}exploratory behavior triggered by a decrease in quality of a known food resource{\textemdash}we found species differences in exploratory behavior that are consistent with selection arising from evolved differences in nest architecture, though the behavioral differences were also strongly influenced by the magnitude of the reward decrease. We had expected that species that build their nests in the open, and hence face a higher fitness cost of worker attrition compared with species that inhabit protective cavities, would be less likely to prolong unrewarded search when food declines in quality. The behavioral data were partially consistent with this expectation. However, at times, the environmental context strongly modulated species differences in behavior that would be expected based on nest architecture. Overall, our results suggest that the resolution of the exploitation-exploration trade-off has been adaptively tuned between species by a number of interacting selection pressures.

}, doi = {10.1007/s00265-020-02938-6}, author = {Young, A.M. and Brockmann, A and Dyer, F.C.} } @article {99941, title = {Adult brain neurons require continual expression of the schizophrenia-risk gene Tcf4 for structural and functional integrity.}, journal = {Transl Psychiatry}, volume = {11}, year = {2021}, month = {2021 Sep 25}, pages = {494}, abstract = {

The schizophrenia-risk gene Tcf4 has been widely studied in the context of brain development using mouse models of haploinsufficiency, in utero knockdown and embryonic deletion. However, Tcf4 continues to be abundantly expressed in adult brain neurons where its functions remain unknown. Given the importance of Tcf4 in psychiatric diseases, we investigated its role in adult neurons using cell-specific deletion and genetic tracing in adult animals. Acute loss of Tcf4 in adult excitatory neurons in vivo caused hyperexcitability and increased dendritic complexity of neurons, effects that were distinct from previously observed effects in embryonic-deficiency models. Interestingly, transcriptomic analysis of genetically traced adult-deleted FACS-sorted Tcf4-knockout neurons revealed that Tcf4 targets in adult neurons are distinct from those in the embryonic brain. Meta-analysis of the adult-deleted neuronal transcriptome from our study with the existing datasets of embryonic Tcf4 deficiencies revealed plasma membrane and ciliary genes to underlie Tcf4-mediated structure-function regulation specifically in adult neurons. The profound changes both in the structure and excitability of adult neurons upon acute loss of Tcf4 indicates that proactive regulation of membrane-related processes underlies the functional and structural integrity of adult neurons. These findings not only provide insights for the functional relevance of continual expression of a psychiatric disease-risk gene in the adult brain but also identify previously unappreciated gene networks underpinning mature neuronal regulation during the adult lifespan.

}, issn = {2158-3188}, doi = {10.1038/s41398-021-01618-x}, author = {Sarkar, Dipannita and Shariq, Mohammad and Dwivedi, Deepanjali and Krishnan, Nirmal and Naumann, Ronald and Bhalla, Upinder Singh and Ghosh, HS} } @article {93672, title = {Adult neural stem cells have latent inflammatory potential that is kept suppressed by to facilitate adult neurogenesis.}, journal = {Sci Adv}, volume = {7}, year = {2021}, month = {2021 May}, abstract = {

Inflammation is known to adversely affect adult neurogenesis, wherein the source of inflammation is largely thought to be extraneous to the neurogenic niche. Here, we demonstrate that the adult hippocampal neural progenitors harbor an inflammatory potential that is proactively suppressed by transcription factor 4 (). Deletion of in hippocampal -expressing progenitors causes loss of proliferative capacity and acquisition of myeloid inflammatory properties. This transformation abolishes their differentiation potential and causes production of detrimental factors that adversely affect niche cells, causing inflammation in the dentate gyrus. Thus, on one hand, deletion causes abrogation of proliferative progenitors leading to reduction of adult neurogenesis, while on the other, their accompanying inflammatory transformation inflicts inflammation in the niche. Taken together, we provide the first evidence for a latent inflammatory potential of adult hippocampal neural progenitors and identify as a critical regulator that facilitates adult neurogenesis via proactive suppression of this detrimental potential.

}, issn = {2375-2548}, doi = {10.1126/sciadv.abf5606}, author = {Shariq, Mohammad and Sahasrabuddhe, Vinaya and Krishna, Sreevatsan and Radha, Swathi and Bellampalli, Ravishankara and Dwivedi, Anukriti and Cheramangalam, Rajit and Reizis, Boris and H{\'e}bert, Jean and Ghosh, Hiyaa S} } @article {93663, title = {Advances in host-based screening for compounds with intracellular anti-mycobacterial activity.}, journal = {Cell Microbiol}, year = {2021}, month = {2021 Apr 04}, pages = {e13337}, abstract = {

Intracellular pathogens interact with host systems in intimate ways to sustain a pathogenic lifestyle. Consequently, these interactions can potentially be targets of host-directed interventions against infectious diseases. In case of tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), while effective anti-tubercular compounds are available, the long treatment duration and emerging drug resistance necessitate identification of new class of molecules with anti-TB activity, as well as new treatment strategies. A significant part of the effort in finding new anti-TB drugs is focused on bacterial targets in bacterial systems. However, the host environment plays a major role in pathogenesis mechanisms and must be considered actively in these efforts. On the one hand, the bacterial origin targets must be relevant and accessible in the host, while on the other hand, new host origin targets required for the bacterial survival can be targeted. Such targets are good candidates for host-directed therapeutics, a strategy gaining traction as an adjunct in TB treatment. In this review, we will summarise the screening platforms used to identify compounds with anti-tubercular activities inside different host environments and outline recent technical advances in these platforms. Finally, while the examples given are specific to mycobacteria, the methods and principles outlined are broadly applicable to most intracellular infections.

}, issn = {1462-5822}, doi = {10.1111/cmi.13337}, author = {Subhash, Neeraja and Sundaramurthy, Varadharajan} } @article {99104, title = {Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations.}, journal = {Cell Rep}, volume = {36}, year = {2021}, month = {2021 Aug 31}, pages = {109648}, abstract = {

Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors activated by the main excitatory neurotransmitter, L-glutamate. mGluR activation by agonists binding in the venus flytrap domain is regulated by positive (PAM) or negative (NAM) allosteric modulators binding to the 7-transmembrane domain (7TM). We report the cryo-electron microscopy structures of fully inactive and intermediate-active conformations of mGlu receptor bound to an antagonist and a NAM or an agonist and a PAM, respectively, as well as the crystal structure of the 7TM bound to a photoswitchable NAM. The agonist induces a large movement between the subunits, bringing the 7TMs together and stabilizing a 7TM conformation structurally similar to the inactive state. Using functional approaches, we demonstrate that the PAM stabilizes a 7TM active conformation independent of the conformational changes induced by agonists, representing an alternative mode of mGlu activation. These findings provide a structural basis for different mGluR activation modes.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2021.109648}, author = {Nasrallah, Chady and Cannone, Giuseppe and Briot, Julie and Rottier, Karine and Berizzi, Alice E and Huang, Chia-Ying and Quast, Robert B and Hoh, Francois and Ban{\`e}res, Jean-Louis and Malhaire, Fanny and Berto, Ludovic and Dumazer, Ana{\"e}lle and Font-Ingles, Joan and G{\'o}mez-Santacana, Xavier and Catena, Juanlo and Kniazeff, Julie and Goudet, Cyril and Llebaria, Amadeu and Pin, Jean-Philippe and Vinothkumar, Kutti R and Lebon, Guillaume} } @article {96748, title = {Allelopathic interaction among rocky intertidal invertebrates: sponge Cinachyrella cf. cavernosa and Zooxanthellate zoanthids Zoanthus sansibaricus}, journal = {Hydrobiologia}, year = {2021}, month = {07/2021}, abstract = {

Intertidal sessile invertebrates experience tough competition for space which they avoid by releasing secondary metabolites (allelochemicals). We investigated the allelopathic interaction between sponge Cinachyrella cf. cavernosa and its neighbour zoanthids Zoanthus sansibaricus over a year on the rocky beach of Anjuna, (Goa) India. A major sterol (beta-sitosterol) was isolated from the sponge, and its natural variability was checked in tagged sponges with and without their competitor zoanthids during the reproductive and non-reproductive months of the sponges. The sponge showed significant variability in the production of beta-sitosterol owing to its spatial competition and asexual reproduction (budding) as predicted by the multiple regression analysis. Zoanthids are known to have dynamic mutualistic association with their autotrophic endosymbionts{\textquoteright} dinoflagellate (Symbiodinium, known as zooxanthellae), which are directly involved in their physiology. The phytagel (TM)-based field assay of sponge{\textquoteright}s bioactive compound (beta-sitosterol) was conducted to check its allelopathic impact on Z. sansibaricus and its symbiotic zooxanthellae (Symbiodinium sp.). Results showed significant bleaching (50-80\%) in the host Z. sansibaricus, resulting from a decrease in symbiotic zooxanthellae count, cell density, chl a and chl c content. This suggests the role of beta-sitosterol as allelochemical of the sponge in preventing the overgrowth of aggressive Z. sansibaricus, possibly by affecting its symbionts. This investigation is not only important to understand the ecological roles of marine-derived allelochemicals but also to allow sustainable bioprospecting of marine resources.

}, doi = {10.1007/s10750-021-04667-x}, author = {Singh, Anshika and Thakur, Narsinh L.} } @article {101897, title = {Analysis of Infection Time Courses Shows CII Levels Determine the Frequency of Lysogeny in Phage 186.}, journal = {Pharmaceuticals (Basel)}, volume = {14}, year = {2021}, month = {2021 Sep 29}, abstract = {

Engineered phage with properties optimised for the treatment of bacterial infections hold great promise, but require careful characterisation by a number of approaches. Phage-bacteria infection time courses, where populations of bacteriophage and bacteria are mixed and followed over many infection cycles, can be used to deduce properties of phage infection at the individual cell level. Here, we apply this approach to analysis of infection of by the temperate bacteriophage 186 and explore which properties of the infection process can be reliably inferred. By applying established modelling methods to such data, we extract the frequency at which phage 186 chooses the lysogenic pathway after infection, and show that lysogenisation increases in a graded manner with increased expression of the lysogenic establishment factor CII. The data also suggest that, like phage λ, the rate of lysogeny of phage 186 increases with multiple infections.

}, issn = {1424-8247}, doi = {10.3390/ph14100998}, author = {Hao, Nan and Agnew, Dylan and Krishna, Sandeep and Dodd, Ian B and Shearwin, Keith E} } @article {94385, title = {Anew medium-sized rupicolous Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) of the C. bangara clade from granite boulder habitats in Krishnagiri, Tamil Nadu, India}, journal = {ZOOTAXA}, volume = {4969}, year = {2021}, month = {05/2021}, pages = {351-366}, abstract = {

We describe a new species of the Cnemaspis bangara clade from a rocky hillock near Kugai Periya Mariamman Temple, Krishnagiri fort, Krishnagiri District of Tamil Nadu, India. Cnemaspis krishnagiriensis sp. nov. can be diagnosed from all other peninsular Indian congeners by its medium body size (maximum SVL 40 mm), heterogeneous dorsal pholidosis, spine-like tubercles absent on flanks; presence of four femoral pores on each thigh separated on either side by nine or 10 poreless scales from three continuous precloacal pores in males; tail with enlarged, strongly keeled, conical tubercles forming four whorls on anterior portion, six tubercles in first whorl, four tubercles in second to fourth whorls, enlarged tubercles restricted to only paravertebral region on rest of the tail; median row of sub-caudals smooth and distinctly enlarged, and a unique colour pattern. The new species can be diagnosed from members of C. bangara clade by the number of dorsal tubercles rows at mid-body, the number of enlarged tubercles in paravertebral rows, the number of ventral scales across belly at mid-body, the number longitudinal ventral scales from mental to cloaca, the number of femoral and precloacal pores and poreless scales separating these series, and subtle colour pattern differences; besides 9.2-17.6 \% uncorrected ND2 sequence divergence. Cnemaspis krishnagiriensis sp. nov. is the fourth member of the recently described bangara clade and is the first that is known to be distributed \<900 m asl.. The discovery of yet another endemic species of Cnemaspis from lower elevations of the Mysore Plateau once again highlights the need of dedicated systematic sampling to uncover the true diversity of Cnemaspis. We also address a nomenclatural issue related to the recently described Cnemaspis stellapulvis Khandekar, Thackeray \& Agarwal.

}, doi = {10.11646/zootaxa.4969.2.7}, author = {Agarwal, Ishan and Thackeray, Tejas and Khandekar, Akshay} } @article {90598, title = {Antagonistic roles for Ataxin-2 structured and disordered domains in RNP condensation.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Mar 10}, abstract = {

Ataxin-2 (Atx2) is a translational control molecule mutated in spinocerebellar ataxia type II and amyotrophic lateral sclerosis. While intrinsically disordered domains (IDRs) of Atx2 facilitate mRNP condensation into granules, how IDRs work with structured domains to enable positive and negative regulation of target mRNAs remains unclear. Using the Targets of RNA-Binding Proteins Identified by Editing technology, we identified an extensive data set of Atx2-target mRNAs in the brain and S2 cells. Atx2 interactions with AU-rich elements in 3{\textquoteright}UTRs appear to modulate stability/turnover of a large fraction of these target mRNAs. Further genomic and cell biological analyses of Atx2 domain deletions demonstrate that Atx2 (1) interacts closely with target mRNAs within mRNP granules, (2) contains distinct protein domains that drive or oppose RNP-granule assembly, and (3) has additional essential roles outside of mRNP granules. These findings increase the understanding of neuronal translational control mechanisms and inform strategies for Atx2-based interventions under development for neurodegenerative disease.

}, issn = {2050-084X}, doi = {10.7554/eLife.60326}, author = {Singh, Amanjot and Hulsmeier, Joern and Kandi, Arvind Reddy and Pothapragada, Sai Shruti and Hillebrand, Jens and Petrauskas, Arnas and Agrawal, Khushboo and Rt, Krishnan and Thiagarajan, Devasena and Jayaprakashappa, Deepa and VijayRaghavan, K and Ramaswami, Mani and Bakthavachalu, Baskar} } @article {96657, title = {Antimicrobial Resistance Profiling and Phylogenetic Analysis of Neisseria gonorrhoeae Clinical Isolates From Kenya in a Resource-Limited Setting}, journal = {Front. Microbiol}, year = {2021}, month = {07/2021}, abstract = {

Background: Africa has one of the highest incidences of gonorrhea. Neisseria gonorrhoeae is gaining resistance to most of the available antibiotics, compromising treatment across the world. Whole-genome sequencing (WGS) is an efficient way of predicting AMR determinants and their spread in the population. Recent advances in next-generation sequencing technologies like Oxford Nanopore Technology (ONT) have helped in the generation of longer reads of DNA in a shorter duration with lower cost. Increasing accuracy of base-calling algorithms, high throughput, error-correction strategies, and ease of using the mobile sequencer MinION in remote areas lead to its adoption for routine microbial genome sequencing. To investigate whether MinION-only sequencing is sufficient for WGS and downstream analysis in resource-limited settings, we sequenced the genomes of 14 suspected N. gonorrhoeae isolates from Nairobi, Kenya.

}, doi = {10.3389/fmicb.2021.647565}, author = {Juma, Meshack and Sankaradoss, Arun and Ndombi, Redcliff and Mwaura, Patrick and Damoda, Tina and Nazir, Junaid and Pandit, Awadhesh and Khurana, Rupsy and Masika, Moses and Chirchir, Ruth and Gachie, John and Krishna, Sudhir and Sowdhamini, Ramanathan and Anzala, Omu and Meenakshi, Iyer S.} } @article {96619, title = {Antiviral therapeutics directed against RNA dependent RNA polymerases from positive-sense viruses.}, journal = {Mol Aspects Med}, year = {2021}, month = {2021 Jul 24}, pages = {101005}, abstract = {

Viruses with positive-sense single stranded RNA (+ssRNA) genomes are responsible for different diseases and represent a global health problem. In addition to developing new vaccines that protect against severe illness on infection, it is imperative to identify new antiviral molecules to treat infected patients. The genome of these RNA viruses generally codes for an enzyme with RNA dependent RNA polymerase (RdRP) activity. This molecule is centrally involved in the duplication of the RNA genome. Inhibition of this enzyme by small molecules will prevent duplication of the RNA genome and thus reduce the viral titer. An overview of the different therapeutic strategies used to inhibit RdRPs from +ssRNA viruses is provided, along with an analysis of these enzymes to highlight new binding sites for inhibitors.

}, issn = {1872-9452}, doi = {10.1016/j.mam.2021.101005}, author = {Bhatia, Sonam and Narayanan, Naveen and Nagpal, Shilpi and Nair, Deepak T} } @article {91464, title = {Assessing woodpeckers as indicators of bird diversity and habitat structure in managed forests}, journal = {BIODIVERSITY AND CONSERVATION}, year = {2021}, month = {03/2021}, abstract = {

Woodpeckers (family Picidae) are a specialised group of insectivores that are sensitive to forest degradation and fragmentation. We evaluated the woodpecker taxa as potential indicators of habitat quality and forest bird diversity in temperate moist hardwood forests (1500-2400 m asl), a threatened biome in the Western Himalaya. 74 forest sites, selected to represent a gradient of anthropogenic use, were surveyed for birds, vegetation structure and proportion of land under dense forest in the surrounding landscape. Individual woodpecker species were observed to quantify their foraging niche preferences. We found that forest sites with higher woodpecker richness were also rich in all other bird species. Further, the richness and abundance of woodpeckers and all other birds were affected by similar habitat variables. Four out of the eight woodpecker species occurring in the study area were found to fit our habitat models suitably, with canopy cover, tree density, and forest proportion proving to be important variables. Behavioural observations showed that the same four woodpecker species significantly preferred larger and taller trees for foraging. Given the difficulty of directly monitoring forest characteristics and total bird diversity over large landscapes, consistent monitoring of sensitive woodpecker species can provide answers to both. Further, as woodpeckers are moderately common and conspicuous birds, areas with high woodpecker diversity can be easily identified and prioritised for conservation.

}, doi = {10.1007/s10531-021-02164-0}, author = {Menon, Tarun and (Shahabuddin, Ghazala} } @article {104420, title = {Astrocytic reactivity triggered by defective autophagy and metabolic failure causes neurotoxicity in frontotemporal dementia type 3.}, journal = {Stem Cell Reports}, volume = {16}, year = {2021}, month = {2021 Nov 09}, pages = {2736-2751}, abstract = {

Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and the endolysosomal pathway in neurons. To dissect the astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) and confirmed our findings in CHMP2B mutant mice. Our data provide mechanistic insights into how defective autophagy causes perturbed mitochondrial dynamics with impaired glycolysis, increased reactive oxygen species, and elongated mitochondrial morphology, indicating increased mitochondrial fusion in FTD3 astrocytes. This shift in astrocyte homeostasis triggers a reactive astrocyte phenotype and increased release of toxic cytokines, which accumulate in nuclear factor kappa b (NF-κB) pathway activation with increased production of CHF, LCN2, and C3 causing neurodegeneration.

}, issn = {2213-6711}, doi = {10.1016/j.stemcr.2021.09.013}, author = {Chandrasekaran, Abinaya and Dittlau, Katarina Stoklund and Corsi, Giulia I and Haukedal, Henriette and Doncheva, Nadezhda T and Ramakrishna, Sarayu and Ambardar, Sheetal and Salcedo, Claudia and Schmidt, Sissel I and Zhang, Yu and Cirera, Susanna and Pihl, Maria and Schmid, Benjamin and Nielsen, Troels Tolstrup and Nielsen, J{\o}rgen E and Kolko, Miriam and Kobol{\'a}k, Julianna and Dinny{\'e}s, Andr{\'a}s and Hyttel, Poul and Palakodeti, Dasaradhi and Gorodkin, Jan and Muddashetty, Ravi S and Meyer, Morten and Aldana, Blanca I and Freude, Kristine K} } @article {95905, title = {At the crossroads: molecular ecology and wildlife conservation.}, journal = {J Indian Inst Sci}, year = {2021}, month = {2021 Jul 05}, pages = {1-2}, issn = {0970-4140}, doi = {10.1007/s41745-021-00246-0}, author = {Ramakrishnan, Uma} } @article {90595, title = {Behavioral Ecology of the Coffee White Stem Borer: Toward Ecology-Based Pest Management of India{\textquoteright}s Coffee Plantations}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, volume = {9}, year = {2021}, month = {02/2021}, abstract = {

India is the seventh largest producer of coffee with 395,000 tons of coffee exports that earn 10 billion US dollars annually. Two varieties of coffee are grown in India, Coffea arabica (arabica) and Coffea canephora (robusta). Xylotrechus quadripes, commonly known as Coffee White Stem Borer (CWSB), is a major pest of arabica, causing yearly crop damage of 17-40 million dollars. Management strategies, over 100 years in development, have provided successful, yet inconsistent solutions due to differences in local climate, elevation, natural enemies, grower diligence, and other factors. In addition, increased pesticide use affects both pests as well as their natural enemies, which has severe negative impacts on the biodiverse regions where coffee is grown. As a result, our goal is to develop an ecology-based solution for long term management of CWSB that reduces the use of pesticides and focuses on the importance of natural enemies and native hosts. In situ behavioral experiments were performed to examine the preferences of CWSB for various local species under field conditions. We found that CWSB beetles were attracted to both healthy arabica and robusta plants, and host plant volatiles played a key role in host selection. In addition, the beetles were attracted to the leaves of these coffee plants and also two species of cut stems from common shade trees; Spathodea campanulata (nandi flame) and Grevillea robusta (silver oak). Beetles were not attracted toward cut stems of Tectona grandis (teak) or Coffea arabica. GC-EAD and EAG experiments were then performed to identify host plant volatiles for these species, and these compounds were tested in field conditions to assess their effectiveness against the known chemical attractant pheromone. We found that the CWSB was attracted to our identified host volatile blend as much as the pheromone lure, although trap catches in general were very low. Having an understanding of the behavioral ecology of this pest can form the basis for new methods that use natural attractant and repellent plants to control the pests, reduce the cost of plantation pest management, and avoid the extensive use of insecticides.

}, doi = {10.3389/fevo.2021.607555}, author = {Rajus, Santosh and Bhagavan, Sriraksha G. and Kharva, Hinal and Rao, Srinivas and Olsson, Shannon B} } @article {95518, title = {Biophysical Properties of the Isolated Spike Protein Binding Helix of Human ACE2.}, journal = {Biophys J}, year = {2021}, month = {2021 Jun 29}, abstract = {

The entry of the SARS-CoV2 virus in human cells is mediated by the binding of its surface spike protein to the human Angiotensin-Converting Enzyme 2 (ACE2) receptor. A 23 residues long helical segment (SBP1) at the binding interface of human ACE2 interacts with viral spike protein and therefore, has generated considerable interest as a recognition element for virus detection. Unfortunately, emerging reports indicate that the affinity of SBP1 to the receptor-binding domain (RBD) of the spike protein is much lower than that of the ACE2 receptor itself. Here, we examine the biophysical properties of SBP1 to reveal factors leading to its low affinity for the spike protein. While SBP1 shows good solubility (solubility \> 0.8 mM), CD spectroscopy shows that it is mostly disordered with some anti-parallel beta-sheet content, and no helicity. The helicity is substantial (\> 20\%) only upon adding high concentrations (>= 20\% v/v) of 2,2,2-trifluoroethanol, a helix-promoter. Fluorescence correlation spectroscopy and single molecule photobleaching studies show that the peptide oligomerizes at concentrations \> 50 nM. We hypothesized that mutating the hydrophobic residues (F28, F32, and F40) of SBP1 which do not directly interact with the spike protein to alanine would reduce peptide oligomerization without affecting its spike binding affinity. While the mutant peptide (SBP1) shows substantially reduced oligomerization propensity, it does not show improved helicity. Our study shows that the failure of efforts so far to produce a short SBP1 mimic with a high affinity for the spike protein is not only due to the lack of helicity, but also due to the heretofore unrecognized problem of oligomerization.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2021.06.017}, author = {Das, Anirban and Vishvakarma, Vicky and Dey, Arpan and Dey, Simli and Gupta, Ankur and Das, Mitradip and Vishwakarma, Krishna Kant and Roy, Debsankar Saha and Yadav, Swati and Kesarwani, Shubham and Venkatramani, Ravindra and Maiti, Sudipta} } @article {83645, title = {The Boggarts of biology: how non-genetic changes influence the genotype.}, journal = {Curr Genet}, volume = {67}, year = {2021}, month = {2020 Oct 10}, pages = {65-77}, abstract = {

The notion that there is a one-one mapping from genotype to phenotype was overturned a long time ago. Along with genotype and environment, {\textquoteright}non-genetic changes{\textquoteright} orchestrated by altered RNA and protein molecules also guide the development of phenotype. The idea that there is a route through which changes in phenotype can lead to changes in genotype impinges on several phenomena of molecular, developmental, evolutionary and applied interest. Phenotypic changes that do not alter the underlying DNA sequence have been studied across model systems (eg: DNA and histone modifications, RNA editing, prion formation) and are known to play an important role in short-term adaptation. However, because of their transient nature and unstable inheritance, the role of such changes in long-term evolution has remained controversial. I classify and review three ways in which non-genetic changes can influence genotype and impact cellular fitness across generations, with an emphasis on the enticing idea that they may act as stepping stones for genetic adaptation. I focus on work from microbial systems and attempt to highlight recent experiments and models that bear on this idea. Overall, I review evidence which suggests that non-genetic changes can impact phenotype via their influence on the genotype, and thus play a role in evolutionary change.

}, issn = {1432-0983}, doi = {10.1007/s00294-020-01108-5}, author = {Samhita, Laasya} } @article {94540, title = {Brain circuits at risk in psychiatric diseases and pharmacological pathways.}, journal = {Therapie}, volume = {76}, year = {2021}, month = {2021 Mar-Apr}, pages = {75-86}, abstract = {

The multiple brain circuits involved in psychiatric diseases may appear daunting, but we prefer to concentrate on a select few, with a particular sensitivity to stress and neurodevelopmental issues, with a clear pharmacotherapy. This review is structured around 1. the key circuits, their role in health and disease, and the neurotransmitters maintaining them, 2. The influence of upbringing, stress, chronobiology, inflammation and infection, 3. The genetic and epigenetic influence on these circuits, particularly regarding copy number variants and neuronal plasticity, 4. The use and abuse of pharmacological agents with the particular risks of stress and chronobiology at critical periods. A major emphasis is placed on the links between hippocampus, prefrontal cortex and amygdala/periaqueductal grey which control specific aspects of cognition, mood, pain and even violence. Some of the research findings were from the innovative medicine initiative (IMI) NEWMEDS, a 22M{\texteuro} academic/industrial consortium on the brain circuits critical for psychiatric disease.

}, issn = {1958-5578}, doi = {10.1016/j.therap.2020.12.005}, author = {Spedding, Michael and Chattarji, Sumantra and Spedding, Charlotte and Jay, Th{\'e}r{\`e}se M} } @article {100626, title = {Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis.}, journal = {Nat Cell Biol}, year = {2021}, month = {2021 Oct 06}, abstract = {

Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery-Arf1, IRSp53 and actin-and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route.

}, issn = {1476-4679}, doi = {10.1038/s41556-021-00767-x}, author = {Moreno-Layseca, Paulina and J{\"a}ntti, Niklas Z and Godbole, Rashmi and Sommer, Christian and Jacquemet, Guillaume and Al-Akhrass, Hussein and Conway, James R W and Kronqvist, Pauliina and Kallionp{\"a}{\"a}, Roosa E and Oliveira-Ferrer, Leticia and Cervero, Pasquale and Linder, Stefan and Aepfelbacher, Martin and Zauber, Henrik and Rae, James and Parton, Robert G and Disanza, Andrea and Scita, Giorgio and Mayor, Satyajit and Selbach, Matthias and Veltel, Stefan and Ivaska, Johanna} } @article {92432, title = {CD24 gene inhibition and TIMP-4 gene upregulation by Imperata cylindrica{\textquoteright}s root extract prevents metastasis of CaSki cells via inhibiting PI3K/Akt/snail signaling pathway and blocking EMT}, journal = {J Ethnopharmacol}, year = {2021}, month = {04/2021}, abstract = {

Ethnopharmacological relevance: Imperata cylindrica (L.) Raeusch (Gramineae) is a medicinal spice traditionally used in the treatment of hypertension and cancer.

Aim of the study: To assess the anti-metastatic potential of the methanol extract of I. cylindrica roots and determined its mechanisms of action.

Material and methods: The growth inhibition activity of I. cylindrica root extract in vitro and in vivo in human cervical cancer. The scratch assay and Boyden Chamber assay were used to determine the anti-migrative and anti-invasion actions of the plant extract. The whole-genome gene expression profiling using RNA-Seq was performed to determine the differentially expressed genes in CaSki cells after exposure to I. cylindrica to identify its targeted genes related to metastasis. Using protein analysis (western blotting) and gene expression analysis (RTqPCR), the targeted pathways of the key genes that were initially identified with RNA-Seq, were evaluated.

Results: I. cylindrica extract showed dose-dependent cytotoxicity in vitro and in vivo in mice bearing tumors. Furthermore, I. cylindrica root extract significantly inhibited cell migration and cell invasion. After the genome-wide transcriptome analysis, we found that important genes involved in cancer progression and metastasis of cervical cancer, that is, CD24 and TIMP-4 were significantly downregulated and upregulated, respectively. Moreover, I. cylindrica root extract significantly inhibited the PI3/AKT/Snail signaling pathway and blocked the EMT of CaSki cells.

Conclusion: These findings provide an anti-metastatic mechanism of action of I. cylindrica root extract toward the human cervical cancer suggesting that this plant maybe developed into selective chemotherapy.

}, doi = {10.1016/j.jep.2021.114111}, author = {Nayim, P and Mbaveng, AT and Sanjukta, M and Rikesh, J and Kuete, V and Krishna, Sudhir} } @article {88158, title = {Centrosome structure and biogenesis: Variations on a theme?}, journal = {Semin Cell Dev Biol}, year = {2021}, month = {2021 Jan 14}, abstract = {

Centrosomes are composed of two orthogonally arranged centrioles surrounded by an electron-dense matrix called the pericentriolar material (PCM). Centrioles are cylinders with diameters of ~250\ nm, are several hundred nanometres in length and consist of 9-fold symmetrically arranged microtubules (MT). In dividing animal cells, centrosomes act as the principal MT-organising centres and they also organise actin, which tunes cytoplasmic MT nucleation. In some specialised cells, the centrosome acquires additional critical structures and converts into the base of a cilium with diverse functions including signalling and motility. These structures are found in most eukaryotes and are essential for development and homoeostasis at both cellular and organism levels. The ultrastructure of centrosomes and their derived organelles have been known for more than half a century. However, recent advances in a number of techniques have revealed the high-resolution structures (at {\r A}-to-nm scale resolution) of centrioles and have begun to uncover the molecular principles underlying their properties, including: protein components; structural elements; and biogenesis in various model organisms. This review covers advances in our understanding of the features and processes that are critical for the biogenesis of the evolutionarily conserved structures of the centrosomes. Furthermore, it discusses how variations of these aspects can generate diversity in centrosome structure and function among different species and even between cell types within a multicellular organism.

}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2020.10.014}, author = {Jana, Swadhin Chandra} } @article {94677, title = {Ceramide structure dictates glycosphingolipid nanodomain assembly and function.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 06 16}, pages = {3675}, abstract = {

Gangliosides in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. How gangliosides are dynamically organized and how they respond to ligand binding is poorly understood. Using fluorescence anisotropy imaging of synthetic, fluorescently labeled GM1 gangliosides incorporated into the plasma membrane of living cells, we found that GM1 with a fully saturated C16:0 acyl chain, but not with unsaturated C16:1 acyl chain, is actively clustered into nanodomains, which depends on membrane cholesterol, phosphatidylserine and actin. The binding of cholera toxin B-subunit (CTxB) leads to enlarged membrane domains for both C16:0 and C16:1, owing to binding of multiple GM1 under a toxin, and clustering of CTxB. The structure of the ceramide acyl chain still affects these domains, as co-clustering with the glycosylphosphatidylinositol (GPI)-anchored protein CD59 occurs only when GM1 contains the fully saturated C16:0 acyl chain, and not C16:1. Thus, different ceramide species of GM1 gangliosides dictate their assembly into nanodomains and affect nanodomain structure and function, which likely underlies many endogenous cellular processes.

}, issn = {2041-1723}, doi = {10.1038/s41467-021-23961-9}, author = {Arumugam, Senthil and Schmieder, Stefanie and Pezeshkian, Weria and Becken, Ulrike and Wunder, Christian and Chinnapen, Dan and Ipsen, John Hjort and Kenworthy, Anne K and Lencer, Wayne and Mayor, Satyajit and Johannes, Ludger} } @article {88161, title = {Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 Jan 19}, pages = {1777}, abstract = {

Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from <= 1 to >= 45\ mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC-MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifications and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein-protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro-survival cellular processes against radiation stress. PPI networks also identified an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifier PXD022380].

}, issn = {2045-2322}, doi = {10.1038/s41598-020-80405-y}, author = {Nishad, S and Chauhan, Pankaj Kumar and Sowdhamini, R and Ghosh, Anu} } @article {93056, title = {CM1-driven assembly and activation of yeast γ-tubulin small complex underlies microtubule nucleation}, journal = {Elife}, volume = {10}, year = {2021}, month = {05/2021}, abstract = {

Microtubule (MT) nucleation is regulated by the γ-tubulin ring complex (γTuRC), conserved from yeast to humans. In Saccharomyces cerevisiae, γTuRC is composed of seven identical γ-tubulin small complex (γTuSC) sub-assemblies, which associate helically to template MT growth. γTuRC assembly provides a key point of regulation for the MT cytoskeleton. Here, we combine crosslinking mass spectrometry, X-ray crystallography, and cryo-EM structures of both monomeric and dimeric γTuSCs, and open and closed helical γTuRC assemblies in complex with Spc110p to elucidate the mechanisms of γTuRC assembly. γTuRC assembly is substantially aided by the evolutionarily conserved CM1 motif in Spc110p spanning a pair of adjacent γTuSCs. By providing the highest resolution and most complete views of any γTuSC assembly, our structures allow phosphorylation sites to be mapped, surprisingly suggesting that they are mostly inhibitory. A comparison of our structures with the CM1 binding site in the human γTuRC structure at the interface between GCP2 and GCP6 allows for the interpretation of significant structural changes arising from CM1 helix binding to metazoan γTuRC.

}, author = {Brilot, AF and Lyon, SA and Zelter, Alex and Viswanath, Shruthi and Maxwell, A and MacCoss, MJ and Muller, EJ and Sali, Andrej and Davis, TN and Agard, DA} } @article {99927, title = {Combatting global grassland degradation}, journal = {NATURE REVIEWS EARTH \& ENVIRONMENT}, year = {2021}, month = {09/2021}, abstract = {

Grasslands provide key ecosystem services, but their protection is often ignored in sustainable policy. This Perspective describes grassland degradation and sets out the steps needed to protect these systems and promote their restoration.

Grasslands are under severe threat from ongoing degradation, undermining their capacity to support biodiversity, ecosystem services and human well-being. Yet, grasslands are largely ignored in sustainable development agendas. In this Perspective, we examine the current state of global grasslands and explore the extent and dominant drivers of their degradation. Socio-ecological solutions are needed to combat degradation and promote restoration. Important strategies include: increasing recognition of grasslands in global policy; developing standardized indicators of degradation; using scientific innovation for effective restoration at regional and landscape scales; and enhancing knowledge transfer and data sharing on restoration experiences. Stakeholder needs can be balanced through standardized assessment and shared understanding of the potential ecosystem service trade-offs in degraded and restored grasslands. The integration of these actions into sustainability policy will aid in halting degradation and enhancing restoration success, and protect the socio-economic, cultural and ecological benefits that grasslands provide.

}, doi = {10.1038/s43017-021-00207-2}, author = {Bardgett, Richard D and Bullock, James M. and Lavorel, Sandra and Manning, Peter and Schaffner, Urs and Ostle, Nicholas and Chomel, Mathilde and Durigan, Giselda and Fry, Ellen L. and Johnson, David and Lavallee, Jocelyn M. and Le Provost, Gaetane and Luo, Shan and Png, Kenny and Sankaran, Mahesh and Hou, Xiangyang and Zhou, Huakun and Ma, Li and Ren, Weibo and Li, Xiliang and Ding, Yong and Li, Yuanheng and Shi, Hongxiao} } @article {88157, title = {Comprehensive annotation and characterization of planarian tRNA and tRNA-derived fragments (tRFs).}, journal = {RNA}, year = {2021}, month = {2021 Jan 14}, abstract = {

tRNA-derived fragments (tRFs) have recently gained a lot of scientific interest due to their diverse regulatory roles in several cellular processes. However, their function in dynamic biological process such as development and regeneration remains unexplored. Here, we show that tRFs are dynamically expressed during planarian regeneration suggesting a possible role for these small RNAs in the regulation of regeneration. In order to characterise planarian tRFs, we first annotated 457 tRNAs in S.mediterranea combining two tRNA prediction algorithms. Annotation of tRNAs facilitated the identification of three main species of tRFs in planarians - the shorter tRF-5s and itRFs, and the abundantly expressed 5{\textquoteright}-tsRNAs. Spatial profiling of tRFs in sequential transverse sections of planarians revealed diverse expression patterns of these small RNAs, including those that are enriched in the head and pharyngeal regions. Expression analysis of these tRF species revealed dynamic expression of these small RNAs over the course of regeneration suggesting an important role in planarian anterior and posterior regeneration. Finally, we show that 5{\textquoteright}-tsRNA in planaria interact with all three SMEDWI proteins and an involvement of Ago1 in the processing of itRFs. In summary, our findings implicate a novel role for tRFs in planarian regeneration, highlighting their importance in regulating complex systemic processes. Our study adds to the catalogue of post-transcriptional regulatory systems in planarian, providing valuable insights on the biogenesis and the function of tRFs in neoblasts and planarian regeneration.

}, issn = {1469-9001}, doi = {10.1261/rna.077701.120}, author = {Lakshmanan, Vairavan and T N, Sujith and Bansal, Dhiru and Padubidri, Shivaprasad V and Palakodeti, Dasaradhi and Krishna, Srikar} } @article {89429, title = {A comprehensive profile of genomic variations in the SARS-CoV-2 isolates from the state of Telangana, India.}, journal = {J Gen Virol}, year = {2021}, month = {2021 Feb 15}, abstract = {

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has rapidly turned into a pandemic, infecting millions and causing 1 157 509 (as of 27 October 2020) deaths across the globe. In addition to studying the mode of transmission and evasion of host immune system, analysing the viral mutational landscape constitutes an area under active research. The latter is expected to impart knowledge on the emergence of different clades, subclades, viral protein functions and protein-protein and protein-RNA interactions during replication/transcription cycle of virus and response to host immune checkpoints. In this study, we have attempted to bring forth the viral genomic variants defining the major clade(s) as identified from samples collected from the state of Telangana, India. We further report a comprehensive draft of all genomic variations (including unique mutations) present in SARS-CoV-2 strain in the state of Telangana. Our results reveal the presence of two mutually exclusive subgroups defined by specific variants within the dominant clade present in the population. This work attempts to bridge the critical gap regarding the genomic landscape and associate mutations in SARS-CoV-2 from a highly infected southern region of India, which was lacking to date.

}, issn = {1465-2099}, doi = {10.1099/jgv.0.001562}, author = {Gupta, Asmita and Sabarinathan, Radhakrishnan and Bala, Pratyusha and Donipadi, Vinay and Vashisht, Divya and Katika, Madhumohan Rao and Kandakatla, Manohar and Mitra, Debashis and Dalal, Ashwin and Bashyam, Murali Dharan} } @article {99111, title = {Computation, wiring, and plasticity in synaptic clusters.}, journal = {Curr Opin Neurobiol}, volume = {70}, year = {2021}, month = {2021 Sep 09}, pages = {101-112}, abstract = {

Synaptic clusters on dendrites are extraordinarily compact computational building blocks. They contribute to key local computations through biophysical and biochemical signaling that utilizes convergence in space and time as an organizing principle. However, these computations can only arise in very special contexts. Dendritic cluster computations, their highly organized input connectivity, and the mechanisms for their formation are closely linked, yet these have not been analyzed as parts of a single process. Here, we examine these linkages. The sheer density of axonal and dendritic arborizations means that there are far more potential connections (close enough for a spine to reach an axon) than actual ones. We see how dendritic clusters draw upon electrical, chemical, and mechano-chemical signaling to implement the rules for formation of connections and subsequent computations. Crucially, the same mechanisms that underlie their functions also underlie their formation.

}, issn = {1873-6882}, doi = {10.1016/j.conb.2021.08.001}, author = {Pulikkottil, Vinu Varghese and Somashekar, Bhanu Priya and Bhalla, Upinder S} } @article {95761, title = {Considerations for Initiating a Wildlife Genomics Research Project in South and South-East Asia}, journal = {JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE}, year = {2021}, month = {07/2021}, abstract = {

Next-generation sequencing (NGS) based genomic studies are revolutionizing the field of wildlife biology. These methods have yielded unprecedented insights for understanding ecology, evolution and conservation of wild populations. Despite the advantages, biodiversity rich regions in the tropics need more NGS-based studies to understand their native species. However, the field has progressed very slowly in these regions due to several challenges, including that most experts in the field are not based here. In this article, we highlight the factors that need to be considered before initiating a wildlife genomics research project with a focus on south and south-east Asia, though several factors apply to other regions as well. We highlight the challenges like policy issues for collecting samples and need for better sequencing and computational infrastructure. Finally, we discuss how global initiatives can help such regions setup NGS-based studies of wildlife.

}, doi = {10.1007/s41745-021-00243-3}, author = {Khan, Anubhab and Tyagi, Abhinav} } @article {92419, title = {Coordination between nucleotide excision repair and specialized polymerase DnaE2 action enables DNA damage survival in non-replicating bacteria}, journal = {Elife}, year = {2021}, month = {04/2021}, abstract = {

ranslesion synthesis (TLS) is a highly conserved mutagenic DNA lesion tolerance pathway, which employs specialized, low-fidelity DNA polymerases to synthesize across lesions. Current models suggest that activity of these polymerases is predominantly associated with ongoing replication, functioning either at or behind the replication fork. Here we provide evidence for DNA damage-dependent function of a specialized polymerase, DnaE2, in replication-independent conditions. We develop an assay to follow lesion repair in non-replicating Caulobacter and observe that components of the replication machinery localize on DNA in response to damage. These localizations persist in the absence of DnaE2 or if catalytic activity of this polymerase is mutated. Single-stranded DNA gaps for SSB binding and low-fidelity polymerase-mediated synthesis are generated by nucleotide excision repair, as replisome components fail to localize in the absence of NER. This mechanism of gap-filling facilitates cell cycle restoration when cells are released into replication-permissive conditions. Thus, such cross-talk (between activity of NER and specialized polymerases in subsequent gap-filling) helps preserve genome integrity and enhances survival in a replication-independent manner.

}, doi = {10.7554/eLife.67552}, author = {Joseph, AM and Daw, S and Sadhir, I and Badrinarayanan, Anjana} } @article {100749, title = {Correction of amygdalar dysfunction in a rat model of fragile X syndrome}, journal = {Cell Reports}, volume = {37}, year = {2021}, month = {10/2021}, pages = {109805}, chapter = {2}, abstract = {

Fragile X syndrome (FXS), a commonly inherited form of autism and intellectual disability, is associated with emotional symptoms that implicate dysfunction of the amygdala. However, current understanding of the pathogenesis of the disease is based primarily on studies in the hippocampus and neocortex, where FXS defects have been corrected by inhibiting group I metabotropic glutamate receptors (mGluRs). Here, we observe that activation, rather than inhibition, of mGluRs in the basolateral amygdala reverses impairments in a rat model of FXS. FXS rats exhibit deficient recall of auditory conditioned fear, which is accompanied by a range of in\ vitro and in\ vivo deficits in synaptic transmission and plasticity. We find presynaptic mGluR5 in the amygdala, activation of which reverses deficient synaptic transmission and plasticity, thereby restoring normal fear learning in FXS rats. This highlights the importance of modifying the prevailing mGluR-based framework for therapeutic strategies to include circuit-specific differences in FXS pathophysiology.

}, doi = {10.1016/j.celrep.2021.109805}, author = {Fernandes, Giselle and Mishra, Pradeep K. and Nawaz, Mohammad Sarfaraz and Donlin-Asp, Paul G. and Rahman, Mohammed Mostafizur and Hazra, Anupam and Kedia, Sonal and Kayenaat, Aiman and Songara, Dheeraj and Wyllie, David J A and Schuman, Erin M. and Kind, Peter C and Chattarji, Sumantra} } @article {91958, title = {Creating clear and informative image-based figures for scientific publications.}, journal = {PLoS Biol}, volume = {19}, year = {2021}, month = {2021 Mar 31}, pages = {e3001161}, abstract = {

Scientists routinely use images to display data. Readers often examine figures first; therefore, it is important that figures are accessible to a broad audience. Many resources discuss fraudulent image manipulation and technical specifications for image acquisition; however, data on the legibility and interpretability of images are scarce. We systematically examined these factors in non-blot images published in the top 15 journals in 3 fields; plant sciences, cell biology, and physiology (n = 580 papers). Common problems included missing scale bars, misplaced or poorly marked insets, images or labels that were not accessible to colorblind readers, and insufficient explanations of colors, labels, annotations, or the species and tissue or object depicted in the image. Papers that met all good practice criteria examined for all image-based figures were uncommon (physiology 16\%, cell biology 12\%, plant sciences 2\%). We present detailed descriptions and visual examples to help scientists avoid common pitfalls when publishing images. Our recommendations address image magnification, scale information, insets, annotation, and color and may encourage discussion about quality standards for bioimage publishing.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3001161}, author = {Jambor, Helena and Antonietti, Alberto and Alicea, Bradly and Audisio, Tracy L and Auer, Susann and Bhardwaj, Vivek and Burgess, Steven J and Ferling, Iuliia and Gazda, Ma{\l}gorzata Anna and Hoeppner, Luke H and Ilangovan, Vinodh and Lo, Hung and Olson, Mischa and Mohamed, Salem Yousef and Sarabipour, Sarvenaz and Varma, Aalok and Walavalkar, Kaivalya and Wissink, Erin M and Weissgerber, Tracey L} } @article {99332, title = {Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders.}, journal = {J Psychiatr Res}, volume = {142}, year = {2021}, month = {2021 Oct}, pages = {54-62}, abstract = {

BACKGROUND: Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer{\textquoteright}s dementia).

METHODS: Modified Waldrop{\textquoteright}s MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).

RESULTS: MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.

CONCLUSION: MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.

}, issn = {1879-1379}, doi = {10.1016/j.jpsychires.2021.07.028}, author = {Sreeraj, Vanteemar S and Puzhakkal, Joan C and Holla, Bharath and Nadella, Ravi Kumar and Sheth, Sweta and Balachander, Srinivas and Ithal, Dhruva and Ali, Furkhan and Viswanath, Biju and Muralidharan, Kesavan and Venkatasubramanian, Ganesan and John, John P and Benegal, Vivek and Murthy, Pratima and Varghese, Mathew and Reddy, Yc Janardhan and Jain, Sanjeev} } @article {101904, title = {A C-terminal ataxin-2 disordered region promotes Huntingtin protein aggregation and neurodegeneration in Drosophila models of Huntington{\textquoteright}s disease.}, journal = {G3 (Bethesda)}, year = {2021}, month = {2021 Oct 09}, abstract = {

The Ataxin-2 (Atx2) protein contributes to the progression of neurodegenerative phenotypes in animal models of amyotrophic lateral sclerosis (ALS), type 2 spinocerebellar ataxia (SCA-2), Parkinson{\textquoteright}s disease, and Huntington{\textquoteright}s disease (HD). However, because the Atx2 protein contains multiple separable activities, deeper understanding requires experiments to address the exact mechanisms by which Atx2 modulates neurodegeneration (ND) progression. Recent work on two ALS models, C9ORF72 and FUS, in Drosophila has shown that a C-terminal intrinsically disordered region (cIDR) of Atx2 protein, required for assembly of ribonucleoprotein (RNP) granules, is essential for the progression of neurodegenerative phenotypes as well as for accumulation of protein inclusions associated with these ALS models. Here, we show that the Atx2-cIDR also similarly contributes to the progression of degenerative phenotypes and accumulation of Huntingtin protein aggregates in Drosophila models of HD. Because Huntingtin is not an established component of RNP granules, these observations support a recently hypothesized, unexpected protein-handling function for RNP granules, which could contribute to the progression of Huntington{\textquoteright}s disease and, potentially, other proteinopathies.

}, issn = {2160-1836}, doi = {10.1093/g3journal/jkab355}, author = {Huelsmeier, Joern and Walker, Emily and Bakthavachalu, Baskar and Ramaswami, Mani} } @article {98080, title = {A CTP-dependent gating mechanism enables ParB spreading on DNA}, journal = {Elife}, volume = {10}, year = {2021}, month = {08/2021}, abstract = {

Proper chromosome segregation is essential in all living organisms. The ParA-ParB-parS system is widely employed for chromosome segregation in bacteria. Previously, we showed that Caulobacter crescentus ParB requires cytidine triphosphate to escape the nucleation site parS and spread by sliding to the neighboring DNA (Jalal et al., 2020). Here, we provide the structural basis for this transition from nucleation to spreading by solving co-crystal structures of a C-terminal domain truncated C. crescentus ParB with parS and with a CTP analog. Nucleating ParB is an open clamp, in which parS is captured at the DNA-binding domain (the DNA-gate). Upon binding CTP, the N-terminal domain (NTD) self-dimerizes to close the NTD-gate of the clamp. The DNA-gate also closes, thus driving parS into a compartment between the DNA-gate and the C-terminal domain. CTP hydrolysis and/or the release of hydrolytic products are likely associated with reopening of the gates to release DNA and recycle ParB. Overall, we suggest a CTP-operated gating mechanism that regulates ParB nucleation, spreading, and recycling.

}, doi = {10.7554/eLife.69676}, author = {Jalal, Adam S. B. and Tran, Ngat T. and Stevenson, Clare E. M. and Chimthanawala, Afroze and Badrinarayanan, Anjana and Lawson, David M. and Le, Tung B. K.} } @article {97217, title = {Cyclic mismatch binding ligands interact with disease-associated CGG trinucleotide repeats in RNA and suppress their translation.}, journal = {Nucleic Acids Res}, year = {2021}, month = {2021 Aug 06}, abstract = {

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a limited expansion of CGG repeats in the FMR1 gene. Degeneration of neurons in FXTAS cell models can be triggered by accumulation of polyglycine protein (FMRpolyG), a by-product of translation initiated upstream to the repeats. Specific aims of our work included testing if naphthyridine-based molecules could (i) block FMRpolyG synthesis by binding to CGG repeats in RNA, (ii) reverse pathological alterations in affected cells and (iii) preserve the content of FMRP, translated from the same FMR1 mRNA. We demonstrate that cyclic mismatch binding ligand CMBL4c binds to RNA structure formed by CGG repeats and attenuates translation of FMRpolyG and formation of nuclear inclusions in cells transfected with vectors expressing RNA with expanded CGG repeats. Moreover, our results indicate that CMBL4c delivery can reduce FMRpolyG-mediated cytotoxicity and apoptosis. Importantly, its therapeutic potential is also observed once the inclusions are already formed. We also show that CMBL4c-driven FMRpolyG loss is accompanied by partial FMRP reduction. As complete loss of FMRP induces FXS in children, future experiments should aim at evaluation of CMBL4c therapeutic intervention in differentiated tissues, in which FMRpolyG translation inhibition might outweigh adverse effects related to FMRP depletion.

}, issn = {1362-4962}, doi = {10.1093/nar/gkab669}, author = {Konieczny, Patryk and Mukherjee, Sanjukta and Stepniak-Konieczna, Ewa and Taylor, Katarzyna and Niewiadomska, Daria and Piasecka, Agnieszka and Walczak, Agnieszka and Baud, Anna and Dohno, Chikara and Nakatani, Kazuhiko and Sobczak, Krzysztof} } @article {89427, title = {Darwinian properties and their trade-offs in autocatalytic RNA reaction networks.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 02 08}, pages = {842}, abstract = {

Discovering autocatalytic chemistries that can evolve is a major goal in systems chemistry and a critical step towards understanding the origin of life. Autocatalytic networks have been discovered in various chemistries, but we lack a general understanding of how network topology controls the Darwinian properties of variation, differential reproduction, and heredity, which are mediated by the chemical composition. Using barcoded sequencing and droplet microfluidics, we establish a landscape of thousands of networks of RNAs that catalyze their own formation from fragments, and derive relationships between network topology and chemical composition. We find that strong variations arise from catalytic innovations perturbing weakly connected networks, and that growth increases with global connectivity. These rules imply trade-offs between reproduction and variation, and between compositional persistence and variation along trajectories of network complexification. Overall, connectivity in reaction networks provides a lever to balance variation (to explore chemical states) with reproduction and heredity (persistence being necessary for selection to act), as required for chemical evolution.

}, issn = {2041-1723}, doi = {10.1038/s41467-021-21000-1}, author = {Ameta, Sandeep and Ars{\`e}ne, Simon and Foulon, Sophie and Saudemont, Baptiste and Clifton, Bryce E and Griffiths, Andrew D and Nghe, Philippe} } @article {84577, title = {Decreased dendritic spine density in posterodorsal medial amygdala neurons of proactive coping rats.}, journal = {Behav Brain Res}, volume = {397}, year = {2021}, month = {2020 Oct 27}, pages = {112940}, abstract = {

There are large individual differences in the way animals, including humans, behaviorally and physiologically cope with environmental challenges and opportunities. Rodents with either a proactive or reactive coping style not only differ in their capacity to adapt successfully to environmental conditions, but also have a differential susceptibility to develop stress-related (psycho)pathologies when coping fails. In this study, we explored if there are structural neuronal differences in spine density in brain regions important for the regulation of stress coping styles. For this, the individual coping styles of wild-type Groningen (WTG) rats were determined using their level of offensive aggressiveness assessed in the resident-intruder paradigm. Subsequently, brains from proactive (high-aggressive) and reactive (low-aggressive) rats were Golgi-cox stained for spine quantification. The results reveal that dendritic spine densities in the dorsal hippocampal CA1 region and basolateral amygdala are similar in rats with proactive and reactive coping styles. Interestingly, however, dendritic spine density in the medial amygdala (MeA) is strikingly reduced in the proactive coping rats. This brain region is reported to be strongly involved in rivalry aggression which is the criterion by which the coping styles in our study are dissociated. The possibility that structural differences in spine density in the MeA are involved in other behavioral traits of distinct coping styles needs further investigation.

}, issn = {1872-7549}, doi = {10.1016/j.bbr.2020.112940}, author = {Anilkumar, Shobha and Patel, Deepika and de Boer, Sietse F and Chattarji, Sumantra and Buwalda, Bauke} } @article {96412, title = {DEELIG: A Deep Learning Approach to Predict Protein-Ligand Binding Affinity.}, journal = {Bioinform Biol Insights}, volume = {15}, year = {2021}, month = {2021}, pages = {11779322211030364}, abstract = {

Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and is a useful measure in drug design. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. Performing such analyses to cover the entire chemical space of small molecules requires intense computational power. Recent developments using deep learning have enabled us to make sense of massive amounts of complex data sets where the ability of the model to "learn" intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated convolutional neural networks to find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies toward a diverse set of ligands without the need of a docked pose or complex as user input. The models were trained and validated using a stringent methodology for feature extraction. Our model performs better in comparison to some existing methods used widely and is suitable for predictions on high-resolution protein crystal (⩽2.5 {\r A}) and nonpeptide ligand as individual inputs. Our approach to network construction and training on protein-ligand data set prepared in-house has yielded significant insights. We have also tested DEELIG on few COVID-19 main protease-inhibitor complexes relevant to the current public health scenario. DEELIG-based predictions can be incorporated in existing databases including RSCB PDB, PDBMoad, and PDBbind in filling missing binding affinity data for protein-ligand complexes.

}, issn = {1177-9322}, doi = {10.1177/11779322211030364}, author = {Ahmed, Asad and Mam, Bhavika and Sowdhamini, Ramanathan} } @article {105156, title = {Deficits Associated With Loss of STIM1 in Purkinje Neurons Including Motor Coordination Can Be Rescued by Loss of Septin 7.}, journal = {Front Cell Dev Biol}, volume = {9}, year = {2021}, month = {2021}, pages = {794807}, abstract = {

Septins are cytoskeletal proteins that can assemble to form heteromeric filamentous complexes and regulate a range of membrane-associated cellular functions. SEPT7, a member of the septin family, functions as a negative regulator of the plasma membrane-localized store-operated Ca entry (SOCE) channel, Orai in neurons, and in human neural progenitor cells. Knockdown of STIM, a Ca sensor in the endoplasmic reticulum (ER) and an integral component of SOCE, leads to flight deficits in that can be rescued by partial loss of SEPT7 in neurons. Here, we tested the effect of reducing and removing SEPT7 in mouse Purkinje neurons (PNs) with the loss of STIM1. Mice with the complete knockout of STIM1 in PNs exhibit several age-dependent changes. These include altered gene expression in PNs, which correlates with increased synapses between climbing fiber (CF) axons and Purkinje neuron (PN) dendrites and a reduced ability to learn a motor coordination task. Removal of either one or two copies of the gene in PNs restored the expression of a subset of genes, including several in the category of neuron projection development. Importantly, the rescue of gene expression in these animals is accompanied by normal CF-PN innervation and an improved ability to learn a motor coordination task in aging mice. Thus, the loss of SEPT7 in PNs further modulates cerebellar circuit function in animals. Our findings are relevant in the context of identifying SEPT7 as a putative therapeutic target for various neurodegenerative diseases caused by reduced intracellular Ca signaling.

}, issn = {2296-634X}, doi = {10.3389/fcell.2021.794807}, author = {Dhanya, Sreeja Kumari and Hasan, Gaiti} } @article {100625, title = {Description of a New Genus with Two New Species of Freshwater Crab (Decapoda: Brachyura: Gecarcinucidae) from the Southwestern Ghats, India.}, journal = {Zool Stud}, volume = {60}, year = {2021}, month = {2021}, pages = {e14}, abstract = {

A new genus of freshwater crab, gen. nov., and two species, sp. nov. (type species) and sp. nov., are described from the Kerala part of the Western Ghats biodiversity hotspot, India. The new genus is superficially similar to and from the same hotspot, but can easily be distinguished by the following suite of carapace and gonopod characters: an inflated carapace with distinct epigastric and postorbital cristae; the third maxilliped exopod has a long flagellum; male sternites 2 and 3 separated by a shallow median groove while sternites 3 and 4 are completely fused, demarcated by shallow oblique grooves; a male first gonopod that is almost straight with a short distal conical distal segment; and a male second gonopod that is as long as the first gonopod with a long and slender distal segment. The two new species can be differentiated from each other by the lateral margins of male pleonal somite 6 and the structure of the male first gonopod.

}, issn = {1810-522X}, doi = {10.6620/ZS.2021.60-14}, author = {Raj, Smrithy and Kumar, Appukuttannair Biju and Ng, Peter K L} } @article {91467, title = {Description of three new species of the genus Mata Distant, 1906 (Hemiptera: Cicadidae: Cicadinae: Oncotympanini) with notes on their natural history from Indian state of Meghalaya, India.}, journal = {Zootaxa}, volume = {4908}, year = {2021}, month = {2021 Jan 13}, pages = {zootaxa.4908.1.1}, abstract = {

Three new species of the Asian genus Mata Distant, 1906 (Hemiptera: Cicadidae) viz. Mata lenonia sp.nov.; Mata ruffordii sp.nov. and Mata meghalayana sp.nov. are described from Indian state of Meghalaya. Keys and taxonomic descriptions of these species are provided with detailed accounts of their natural history and acoustics.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4908.1.1}, author = {Sarkar, Vivek and Mahapatra, Cuckoo and Mohapatra, Pratyush P and Nair, Manoj V and Kunte, Krushnamegh} } @article {100628, title = {Description of two new species of the tribe Chrysillini Simon, 1901 from India (Araneae: Salticidae)}, journal = {ARTHROPODA SELECTA }, volume = {30}, year = {2021}, month = {06/2021}, pages = {230-238}, chapter = {2}, abstract = {

Two new species of the jumping spiders, Phintella cholkei sp.n. (male female) and Icius tukarami sp.n. (male), from Maharashtra state, India are described. Their detailed morphological descriptions, diagnoses and illustrations of the copulatory organs are provided. Yet, observations on maternal care and habitat of P. cholkei sp.n. are provided as well.

}, doi = {10.15298/arthsel.30.2.10}, author = {Prajapati, Dhruv A. and Kumbhar, Somnath B. and Caleb, John T. D. and Sanap, Rajesh V and Kamboj, Ravi D.} } @article {99101, title = {Design, Synthesis and Conformational Studies of Cyclic Tetrapeptides having beta gamma Fused Turns as HDAC Inhibitors}, journal = {CHEMISTRYSELECT}, volume = {6}, year = {2021}, month = {08/2021}, pages = {7887-7893}, abstract = {

Histone deacetylases (HDACs) belong to a class of major targets for the development of anticancer drugs for which cyclic peptide-based molecules are attracting wide attention. Here we show the synthesis, conformational and in silico analysis of tetrahydrofuran amino acid (TAA) based 15-membered cyclic tetrapeptides (CTPs) containing hydroxamic acid side chain as potential HDAC inhibitors. NMR based solution studies in protected and deprotected forms reveal that the macrocycles are stabilized by 10-membered beta-turn as well as a 7-membered gamma-turn. This type of fused structures within the same macrocycle is not frequently sighted. Our initial in silico docking results indicated that the hydroxamic acid protected CTPs show promising binding with the class-1 HDACs. We also noticed that the C-chain with hydroxamic functional group attached on the ornithine sidechain did not affect the core structure of the peptide ring. Moreover, some of these cyclic tetrapeptides with hydroxamic acid side chain exhibited an induction of acetylation of histones on preliminary cell-based experiments. Our initial results provide an insight into the development of HDAC inhibitors based on the CTPs with novel beta gamma fused turns which have not been explored yet.

}, doi = {10.1002/slct.202102417}, author = {Ghosh, Uttam and Basu, Moumita and Pal, Sudip and Meena, Sanjeev and Datta, Dipak and Ampapathi, Ravi Sankar and Kundu, Tapas K. and Singh, Gajendra and Chakraborty, Tushar Kanti} } @article {99937, title = {Destabilization of polar interactions in the prion protein triggers misfolding and oligomerization.}, journal = {Protein Sci}, year = {2021}, month = {2021 Sep 23}, abstract = {

The prion protein (PrP) misfolds and oligomerizes at pH 4 in the presence of physiological salt concentrations. Low pH and salt cause structural perturbations in the monomeric prion protein that leads to misfolding and oligomerization. However, the changes in stability within different regions of the PrP prior to oligomerization are poorly understood. In this study, we have characterized the local stability in PrP at high resolution using amide temperature coefficients (T ) measured by NMR spectroscopy. The local stability of PrP was investigated under native as well as oligomerizing conditions. We have also studied the rapidly oligomerizing PrP variant (Q216R) and the protective PrP variant (A6). We report that at low pH, salt destabilizes PrP at several polar residues, and the hydrogen bonds in helices α2 and α3 are weakened. In addition, salt changes the curvature of the α3 helix, which likely disrupts α2-α3 contacts and leads to oligomerization. These results are corroborated by the T values of rapidly oligomerizing Q216R-PrP. The poly-alanine substitution in A6-PrP stabilizes α2, which prevents oligomerization. Altogether, these results highlight the importance of native polar interactions in determining the stability of PrP and reveal the structural disruptions in PrP that lead to misfolding and oligomerization. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.4188}, author = {Bhate, Suhas H and Udgaonkar, Jayant B and Das, Ranabir} } @article {95763, title = {Diet Drives Differences in Reproductive Synchrony in Two Sympatric Mountain Ungulates in the Himalaya}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, volume = {9}, year = {2021}, month = {06/2021}, abstract = {

Ungulates in higher latitudes and altitudes experience sharp seasonal changes in forage abundance and quality. In response, ungulates show varying degrees of synchrony in reproduction. Diet type has been hypothesized to be a determinant of differences in reproductive synchrony. Analyses at global scales using proxies of plant phenology such as climate, latitude and Normalized Difference Vegetation Index (NDVI) have found no evidence in support because such proxies do not capture differences in phenology among plant taxa at local scales. We compared seasonal variations in diet quality with reproductive synchrony in the Himalayan musk deer (Moschus chrysogaster), a browser, and the Himalayan goral (Naemorhedus goral), a grazer, in mid-altitude Himalaya. We also compared seasonal variations in physiological stress using fecal glucocorticoid metabolite (FGM). We identified different stages of female reproductive cycle using fecal concentrations of metabolites of estradiol, pregnanediol-3-glucuronide (PdG) and testosterone and used fecal crude protein (CP) as an indicator of diet quality. In musk deer, fecal estradiol and PdG concentrations showed a dispersed estrous and parturition, respectively. Goral had a more synchronized estrous and parturition. Estrous cycles in both species occurred when diet quality was poor, but parturition occurred when diet quality was high. Greater seasonality in reproduction in goral is driven by sharp phenological changes in graminoids on which it feeds, compared to slow changes in browse on which musk deer feeds. Thus, we show that diet type drives the differences in reproductive synchrony in these two sympatric species. Spring and summer with highest diet quality were times of highest stress in both the ungulates. We hypothesize predation pressure from feral dogs and resource competition with livestock as plausible explanations for this, which need to be tested in future. Our findings also highlight the need for studying relationships among plant phenology, diet type and reproductive biology of ungulates at local scales if we are to understand species responses to global phenomena such as climate change.

}, doi = {10.3389/fevo.2021.647465}, author = {Srivastava, Tanushree and Kumar, Ajith and Kumar, Vinod and Umapathy, Govindhaswamy} } @article {89660, title = {Differential activation of JAK-STAT signaling reveals functional compartmentalization in blood progenitors.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Feb 17}, abstract = {

Blood cells arise from diverse pools of stem and progenitor cells. Understanding progenitor heterogeneity is a major challenge. The larval lymph gland is a well-studied model to understand blood progenitor maintenance and recapitulates several aspects of vertebrate hematopoiesis. However in-depth analysis has focused on the anterior lobe progenitors (AP), ignoring the posterior progenitors (PP) from the posterior lobes. Using expression mapping, developmental and transcriptome analysis we reveal PP heterogeneity and identify molecular-genetic tools to study this abundant progenitor population. Functional analysis shows that PP resist differentiation upon immune challenge, in a JAK-STAT-dependent manner. Upon wasp parasitism, AP downregulate JAK-STAT signaling and form lamellocytes. In contrast, we show that PP activate STAT92E and remain undifferentiated, promoting survival. knockdown or genetically reducing JAK-STAT signaling permits PP lamellocyte differentiation. We discuss how heterogeneity and compartmentalization allow functional segregation in response to systemic cues and could be widely applicable.

}, issn = {2050-084X}, doi = {10.7554/eLife.61409}, author = {Rodrigues, Diana and Renaud, Yoan and VijayRaghavan, K and Waltzer, Lucas and Inamdar, Maneesha S} } @article {94389, title = {Differential chromatin accessibility landscape of gain-of-function mutant p53 tumours.}, journal = {BMC Cancer}, volume = {21}, year = {2021}, month = {2021 Jun 05}, pages = {669}, abstract = {

BACKGROUND: Mutations in TP53 not only affect its tumour suppressor activity but also exerts oncogenic gain-of-function activity. While the genome-wide mutant p53 binding sites have been identified in cancer cell lines, the chromatin accessibility landscape driven by mutant p53 in primary tumours is unknown. Here, we leveraged the chromatin accessibility data of primary tumours from The Cancer Genome Atlas (TCGA) to identify differentially accessible regions in mutant p53 tumours compared to wild-type p53 tumours, especially in breast and colon cancers.

RESULTS: We identified 1587 lost and 984 gained accessible chromatin regions in breast, and 1143 lost and 640 gained regions in colon cancers. However, only less than half of those regions in both cancer types contain sequence motifs for wild-type or mutant p53 binding. Whereas, the remaining showed enrichment for master transcriptional regulators, such as FOX-Family TFs and NF-kB in lost and SMAD and KLF TFs in gained regions of breast. In colon, ATF3 and FOS/JUN TFs were enriched in lost, and CDX family TFs and HNF4A in gained regions. By integrating the gene expression data, we identified known and novel target genes regulated by the mutant p53.

CONCLUSION: This study reveals the direct and indirect mechanisms by which gain-of-function mutant p53 targets the chromatin and subsequent gene expression patterns in a tumour-type specific manner. This furthers our understanding of the impact of mutant p53 in cancer development.

}, issn = {1471-2407}, doi = {10.1186/s12885-021-08362-x}, author = {Dhaka, Bhavya and Sabarinathan, Radhakrishnan} } @article {91959, title = {Distance estimation by Asian honey bees in two visually different landscapes.}, journal = {J Exp Biol}, year = {2021}, month = {2021 Apr 01}, abstract = {

Honey bees estimate distances to food sources using image motion experienced on the flight path and they use this measure to tune the waggle phase duration in their dance communication. Most studies on the dance-related odometer are based on experiments with foragers trained into small tunnels with black and white patterns which allowed quantifiable changes in the optic flow. In this study, we determined the calibration curves of two Asian honey bee species, and , in two different natural environments with clear differences in the vegetation conditions and hence visual contrast. We found that the dense vegetation condition (with higher contrast) elicited a more rapid increase in the waggle phase duration with distance than the sparse vegetation in but not in Our findings suggest that contrast sensitivity of the waggle dance odometer might vary among honey bee species.

}, issn = {1477-9145}, doi = {10.1242/jeb.242404}, author = {George, Ebi Antony and Thulasi, Neethu and Kohl, Patrick L and Suresh, Sachin and Rutschmann, Benjamin and Brockmann, Axel} } @article {89987, title = {Distinct actin-dependent nanoscale assemblies underlie the dynamic and hierarchical organization of E-cadherin.}, journal = {Curr Biol}, year = {2021}, month = {2021 Feb 12}, abstract = {

Cadherins are transmembrane adhesion proteins required for the formation of cohesive tissues. Intracellular interactions of E-cadherin with the Catenin family proteins, α- and β-catenin, facilitate connections with the cortical actomyosin network. This is necessary for maintaining the integrity of cell-cell adhesion in epithelial tissues. The supra-molecular architecture of E-cadherin is an important feature of its adhesion function; cis and trans interactions of E-cadherin are deployed to form clusters, both in cis and trans. Studies in Drosophila embryo have also shown that Drosophila E-cadherin (dE-cad) is organized as finite-sized dynamic clusters that localize with actin patches at cell-cell junctions, in continuous exchange with the extra-junctional pool of dE-cad surrounding the clusters. Here, we use the ectopic expression of dE-cad in larval hemocytes, which lack endogenous dE-cad to recapitulate functional cell-cell junctions in a convenient model system. We find that, while dE-cad at cell-cell junctions in hemocytes exhibits a clustered trans-paired organization similar to that reported previously in embryonic epithelial tissue, extra-junctional dE-cad is also organized as relatively immobile nanoclusters as well as more loosely packed diffusive oligomers. Oligomers are promoted by cis interactions of the ectodomain, and their growth is counteracted by the activity of cortical actomyosin. Oligomers in turn promote assembly of dense nanoclusters that require cortical actomyosin activity. Thus, cortical actin activity remodels oligomers and generates nanoclusters. The requirement for dynamic actin in the organization of dE-cad at the nanoscale may provide a mechanism to dynamically tune junctional strength.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2021.01.059}, author = {Chandran, Rumamol and Kale, Girish and Philippe, Jean-Marc and Lecuit, Thomas and Mayor, Satyajit} } @article {96751, title = {Distinct temporal expression of GW182 (TNRC6A) in neurons regulates dendritic arborization.}, journal = {J Cell Sci}, year = {2021}, month = {2021 Jul 30}, abstract = {

Precise development of the dendritic architecture is a critical determinant of mature neuronal circuitry. MicroRNA-mediated regulation of protein synthesis plays a crucial role in dendritic morphogenesis but the role of miRISC protein components in this process is less studied. Here, we show an important role of a key miRISC protein GW182 paralog TNRC6A in the regulation of dendritic growth. We have identified a distinct brain region specific spatio-temporal expression pattern of GW182 during rat postnatal development. We found that the window of peak GW182 expression coincides with the period of extensive dendritic growth, both in the hippocampus and cerebellum. Perturbation of GW182 function during a specific temporal window resulted in reduced dendritic growth of cultured hippocampal neurons. Mechanistically, we show that GW182 modulates dendritic growth by regulating global somato-dendritic translation, and actin cytoskeletal dynamics of developing neurons. Furthermore, we found that GW182 affects dendritic architecture by regulating the expression of actin modulator LIMK1. Taken together, our data reveal a previously undescribed neurodevelopmental expression pattern of GW182 and its role in dendritic morphogenesis, through both translational control and actin cytoskeletal rearrangement.

}, issn = {1477-9137}, doi = {10.1242/jcs.258465}, author = {Nawalpuri, Bharti and Sharma, Arpita and Chattarji, Sumantra and Muddashetty, Ravi S} } @article {94157, title = {Disulfide-Rich Cyclic Peptides from Protect against β-Amyloid Toxicity and Oxidative Stress in Transgenic .}, journal = {J Med Chem}, year = {2021}, month = {2021 May 28}, abstract = {

Neurotoxic aggregation of β-amyloid (Aβ) peptides is a hallmark of Alzheimer{\textquoteright}s disease and increased reactive oxygen species (ROS) is an associated process. In the present study, we report the neuroprotective effects of disulfide-rich, circular peptides from () (butterfly pea) on Aβ-induced toxicity in transgenic . Cyclotides (\~{}30 amino acids long) are a special class of cyclic cysteine knot peptides. We show that cyclotide-rich fractions from different plant tissues delay Aβ-induced paralysis in the transgenic CL4176 strain expressing the human muscle-specific Aβ gene. They also improved Aβ-induced chemotaxis defects in CL2355 strain expressing Aβ in the neuronal cells. ROS assay suggests that this protection is likely mediated by the inhibition of Aβ oligomerization. Furthermore, Aβ deposits were reduced in the CL2006 strain treated with the fractions. The study shows that cyclotides from could be a source of a novel pharmacophore scaffold against neurodegenerative diseases.

}, issn = {1520-4804}, doi = {10.1021/acs.jmedchem.1c00033}, author = {Kalmankar, Neha V and Hari, Hrudya and Sowdhamini, Ramanathan and Venkatesan, Radhika} } @article {99940, title = {Diversifying on the Ark: multiple new endemic lineages of dwarf geckos from the Western Ghats provide insights into the systematics and biogeography of South Asian (Reptilia: Squamata).}, journal = {Zool Res}, volume = {42}, year = {2021}, month = {2021 Nov 18}, pages = {675-691}, abstract = {

The highly speciose gekkonid genus Strauch, 1887 is polyphyletic, with three distantly related and geographically isolated clades from Africa, South Asia (SA), and Southeast Asia. At present, there are 85 known species within SA , although the number continues to increase rapidly with focused surveys and rigorous taxonomic work. Recent studies have provided valuable insights into the diversity and evolutionary history of SA ; however, most of these studies lack sufficient sampling in the Western Ghats (WG), where the genus has its greatest diversity. We addressed this research gap by conducting extensive sampling across the WG and re-examining museum specimens, thus providing a systematic account of various extant species along with their distribution and natural history. We described 12 new species and a southern WG endemic clade of SA Ten of the newly described species are endemic to the forests of the southern WG. We also identified 10 well-supported subclades that can be separated across morphological, geographic, and phylogenetic axes. A time-calibrated phylogeny and ancestral area reconstructions confirmed the Paleocene origin of SA in the WG and provide insights into its evolutionary history and biogeography. The discovery of multiple endemic and deeply divergent lineages further highlights the evolutionary significance of the WG for lizards.

}, issn = {2095-8137}, doi = {10.24272/j.issn.2095-8137.2021.074}, author = {Pal, Saunak and Mirza, Zeeshan A and Dsouza, Princia and Shanker, Kartik} } @article {94158, title = {Diversity and prevalence of ANTAR RNAs across actinobacteria.}, journal = {BMC Microbiol}, volume = {21}, year = {2021}, month = {2021 May 29}, pages = {159}, abstract = {

BACKGROUND: Computational approaches are often used to predict regulatory RNAs in bacteria, but their success is limited to RNAs that are highly conserved across phyla, in sequence and structure. The ANTAR regulatory system consists of a family of RNAs (the ANTAR-target RNAs) that selectively recruit ANTAR proteins. This protein-RNA complex together regulates genes at the level of translation or transcriptional elongation. Despite the widespread distribution of ANTAR proteins in bacteria, their target RNAs haven{\textquoteright}t been identified in certain bacterial phyla such as actinobacteria.

RESULTS: Here, by using a computational search model that is tuned to actinobacterial genomes, we comprehensively identify ANTAR-target RNAs in actinobacteria. These RNA motifs lie in select transcripts, often overlapping with the ribosome binding site or start codon, to regulate translation. Transcripts harboring ANTAR-target RNAs majorly encode proteins involved in the transport and metabolism of cellular metabolites like sugars, amino acids and ions; or encode transcription factors that in turn regulate diverse genes.

CONCLUSION: In this report, we substantially diversify and expand the family of ANTAR RNAs across bacteria. These findings now provide a starting point to investigate the actinobacterial processes that are regulated by ANTAR.

}, issn = {1471-2180}, doi = {10.1186/s12866-021-02234-x}, author = {Mehta, Dolly and Ramesh, Arati} } @article {102992, title = {Diversity of Rhizo-Bacteriome of Crocus sativus Grown at Various Geographical Locations and Cataloging of Putative PGPRs}, journal = {FRONTIERS IN SUSTAINABLE FOOD SYSTEMS}, year = {2021}, month = {11/2021}, abstract = {

Earlier plant growth promoting rhizo-bacteria (PGPRs) were isolated from the plants, by cultivation based techniques and the interaction was mostly thought to be bilateral. The routine bilateral study, with no information on the associated microbiome, could be one of the reasons for the limited success of PGPRs in the field conditions. Keeping in view the role of PGPRs in rhizo-bacteriome on the growth and production of plant, the present study was aimed at studying the diversity of the rhizo-bacteriome of saffron grown across three geographical locations namely Kashmir, Kishtwar and Bengaluru. Variation in the rhizo-bacteriome of saffron growing across 10 different sites from 3 geographical locations was studied using 16S rDNA amplicon metagenomic sequencing. 16 bacterial phyla, 261 genera and 73 bacterial species were cataloged from all the rhizosphere samples. Proteobacteria was a dominant phylum in all the rhizosphere samples. Rhizo-bacteriome of saffron grown in Kishtwar was found to be significantly different from the rhizo-bacteriome of saffron grown in Kashmir and Bengaluru. Interestingly, the rhizo-bacteriome of saffron grown in Bengaluru was very similar to the saffron grown in Kashmir, thereby indicating that the rhizo-bacteriome in saffron is "plant driven" as the corm sown in Bengaluru were from Kashmir. Despite variation in rhizo-bacteriome, core rhizo-bacteriome in saffron was identified that was represented by 53 genera and eight bacterial species belonging to 11 phyla irrespective of their geographical distribution. In addition, 21 PGPRs were reported for the first time from the saffron rhizosphere. The high yielding saffron field Wuyan was found to have the highest number of PGPRs; this indicates that the presence of PGPR is important for yield enhancement than diversity. The two PGPR Rhizobium leguminosarum and Luteibacter rhizovicinus were reported from all the locations except Kishtwar that had escaped isolation in our previous attempts using cultivation based techniques. It is being proposed instead of going for random isolation and screening for PGPRs from plant rhizosphere, an alternate strategy using metagenomic cataloging of the rhizo-bacteriome community and cultivation of the dominant PGPR should be undertaken. This strategy will help in the selection of dominant PGPRs, specific to the plant in question.

}, author = {Ambardar, Sheetal and Bhagat, Nancy and Vakhlu, Jyoti and Gowda, Malali} } @article {89125, title = {Dominance behaviour and division of labour in the tropical primitively eusocial wasp Ropalidia cyathiformis}, journal = {INSECTES SOCIAUX}, year = {2021}, month = {01/2021}, abstract = {

Primitively eusocial insects exhibit reproductive division of labour such that one or a small number of individuals monopolize reproduction while the remaining function as non-reproductive workers. They also exhibit non-reproductive division of labour such that some workers primarily perform the extra-nidal tasks of foraging, while others primarily perform the intra-nidal tasks of feeding larvae, building the nest and other nest maintenance activities. In some species, queens regulate both reproductive as well as non-reproductive division of labour by means of their dominance behavior toward the workers. Here we show that in the primitively eusocial species R. cyathiformis, (1) the queen shows significantly more aggression towards the potential queen (PQ) than to the rest of the workers; (2) the PQ shows significantly more aggression towards the workers than they show to each other; (3) the activities of the workers such as bringing food and feeding the larvae continue unabated in the absence of the queen; (4) the amount of dominance received by a worker does not predict her rate of foraging; (5) there is a positive correlation between workers{\textquoteright} rates of bringing food and the rates at which they themselves feed the larvae. We suggest that while queen (along with PQ) regulates reproductive division of labour, dominance behavior is not used to regulate the non-reproductive activities of the workers such as bringing food and feeding the larvae; these are self-regulated by individual workers by themselves.

}, doi = {10.1007/s00040-020-00803-3}, author = {Unnikrishnan, S and Gadagkar, R} } @article {100627, title = {Dragonflies and damselflies (Insecta: Odonata) of Karimganj District, Assam, India with four additions to the Indian checklist}, journal = {ORIENTAL INSECTS }, year = {2021}, month = {10/2021}, abstract = {

Situated at the intersection of the Himalayan and Indo-Chinese biodiversity hotspots, Northeast India is one of the most biodiversity rich areas of South Asia. Despite this, insects such as dragonflies and damselflies (Order: Odonata) of this region remain poorly studied causing an impediment to their conservation assessments. We conducted long-term surveys to study odonate diversity of the Karimganj District, Assam, India bordering the states of Tripura and Mizoram, and the country of Bangladesh. Here, we publish reports of eight species: four new to India Ceriagrion calamineum, Nannophyopsis clara, Phyllothemis eltoni, and Zyxomma breviventre, and four noteworthy species newly recorded from the state: Megalogomphus smithii, Orientogomphus indicus, Pseudothemis zonata, and Sarasaeschna khasiana. We recorded total 97 odonate species during our surveys. We provide the checklist of Odonata of Assam based on our surveys and literature.

}, doi = {10.1080/00305316.2021.1982787}, author = {Joshi, Shantanu and Gassah, Rejoice and Ismavel, Vijay Anand} } @article {100624, title = {Duox generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in tracheoblasts.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Oct 08}, abstract = {

Progenitors of the thoracic tracheal system of adult (tracheoblasts) arrest in G2 during larval life and rekindle a mitotic program subsequently. G2 arrest is dependent on ATR-dependent phosphorylation of Chk1 that is actuated in the absence of detectable DNA damage. We are interested in the mechanisms that activate ATR/Chk1 (Kizhedathu et al., 2018, 2020). Here we report that levels of reactive oxygen species (ROS) are high in arrested tracheoblasts and decrease upon mitotic re-entry. High ROS is dependent on expression of Duox, an HO generating-Dual Oxidase. ROS quenching by overexpression of Superoxide Dismutase 1, or by knockdown of Duox, abolishes Chk1 phosphorylation and results in precocious proliferation. Tracheae deficient in Duox, or deficient in both Duox and regulators of DNA damage-dependent ATR/Chk1 activation (ATRIP/TOPBP1/ Claspin), can induce phosphorylation of Chk1 in response to micromolar concentrations of HO in minutes. The findings presented reveal that HO activates ATR/Chk1 in tracheoblasts by a non-canonical, potentially direct, mechanism.

}, issn = {2050-084X}, doi = {10.7554/eLife.68636}, author = {Kizhedathu, Amrutha and Chhajed, Piyush and Yeramala, Lahari and Sain Basu, Deblina and Mukherjee, Tina and Vinothkumar, Kutti R and Guha, Arjun} } @article {95320, title = {An early cortical progenitor-specific mechanism regulates thalamocortical innervation.}, journal = {J Neurosci}, year = {2021}, month = {2021 Jun 28}, abstract = {

The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. We report that when transcription factor Lhx2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant ingrowth into the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific mutants displays atrophy and by postnatal day (P) 7, sensory innervation to the cortex is nearly eliminated leading to a loss of the somatosensory barrels. Strikingly, these phenotypes do not manifest if Lhx2 is lost in postmitotic subplate neurons, and the transcriptomic dysregulation in the subplate resulting from postmitotic loss of Lhx2 is vastly distinct from that seen when Lhx2 is lost in progenitors. These results demonstrate a mechanism operating in subplate progenitors that has profound consequences on the growth of thalamocortical axons into the cortex.Thalamocortical nerves carry sensory information from the periphery to the cortex. When they first grow into the embryonic cortex, they "wait" at the subplate, a structure critical for the guidance and eventual connectivity of thalamic axons with their cortical targets. How the properties of subplate neurons are regulated is unclear. We report that transcription factor Lhx2 is required in the progenitor "mother" cells of the cortical primordium when they are producing their "daughter" subplate neurons, in order for the thalamocortical pathway to wait at the subplate. Without Lhx2 function in subplate progenitors, thalamocortical axons grow past the subplate, entering the cortical plate prematurely. This is followed by their eventual attrition, and consequently a profound loss of sensory innervation of the mature cortex.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0226-21.2021}, author = {Pal, Suranjana and Dwivedi, Deepanjali and Pramanik, Tuli and Godbole, Geeta and Iwasato, Takuji and Jabaudon, Denis and Bhalla, Upinder S and Tole, Shubha} } @article {95318, title = {Effect of nanoparticle exposure in a living system: probed by quantification of Fetuin-B in plasma proteome and kidney tissue imaging using MALDI imaging mass spectrometry in a rat model}, journal = {JOURNAL OF NANOPARTICLE RESEARCH}, volume = {23}, year = {2021}, month = {06/2021}, chapter = {6}, abstract = {

Nanoparticles have gained importance in various biomedical field viz cosmetics, diagnostics, therapeutics, and food additives. Due to small size, NPs penetrate tissues and cells, thereby interacting with biomolecules such as proteins and nucleic acids. This raises the major concern to investigate the effect of NPs in a living system. Previously, we reported downregulation of Fetuin-B in rat plasma, with the increasing dose level of NP-Fe-4(P2O7)(3), in rats treated with NP-Fe-4(P2O7)(3) as a food-fortificant. In the present study, we validated the dose response of FetuinB in rats exposed to NP-Fe-4(P2O7)(3), NP-ZnO, and NP-SiO2. Fetuin-B showed similar dose responses in all the groups irrespective of their physicochemical properties. Previously, we hypothesized that the immune response was triggered upon exposure to NP-Fe-4(P2O7)(3) in vivo, which led to the differential regulation of Fetuin-B. To evaluate the hypothesis, immunological response was assessed in rats by estimating the pro-inflammatory cytokines in plasma. We observed Interleukin-la and Interleukin-1 beta increased with the increasing dose levels of the three NPs. The impact of NPs on the proteomic profile in the kidney tissues of rats exposed to three NPs, showed differential spatial distribution of a-Enolase across the medulla and the cortex region with respect to the control group, suggesting an overexpression of a-Enolase. Overexpression of a-Enolase might be an indicative of cellular apoptosis in response to cytotoxicity caused due to NP perforation across the cellular membrane. In the present study, we propose that Fetuin-B might be considered a plasma biomarker to detect nanotoxicity at an early stage in a living system.

}, doi = {10.1007/s11051-021-05251-z}, author = {Srinivasu, BY and Arumugaperumal, Arun and Mitra, Amrita and Muralidharan, Monita and Das, Rajdeep and Mandal, Amit Kumar} } @article {93670, title = {Electrophysiological, behavioural and biochemical effect of Ocimum basilicum oil and its constituents methyl chavicol and linalool on Musca domestica L.}, journal = {Environ Sci Pollut Res Int}, year = {2021}, month = {2021 May 08}, abstract = {

Ocimum basilicum essential oil (EO) was evaluated for its biological effects on M. domestica. Characterization of O. basilicum EO revealed the presence of methyl chavicol (70.93\%), linalool (9.34\%), epi-α-cadinol (3.69 \%), methyl eugenol (2.48\%), γ-cadinene (1.67\%), 1,8-cineole (1.30\%) and (E)-β-ocimene (1.11\%). The basil EO and its constituents methyl chavicol and linalool elicited a neuronal response in female adults of M. domestica. Adult female flies showed reduced preference to food source laced with basil EO and methyl chavicol. Substrates treated with EO and methyl chavicol at 0.25\% resulted in an oviposition deterrence of over 80\%. A large ovicidal effect was found for O. basilicum EO (EC 9.74 mg/dm) followed by methyl chavicol (EC 10.67 mg/dm) and linalool (EC 13.57 mg/dm). Adults exposed to EO (LD 10.01 μg/adult) were more susceptible to contact toxicity than to methyl chavicol and linalool (LD 13.62 μg/adult and LD 43.12 μg/adult respectively). EO and its constituents methyl chavicol and linalool also induced the detoxifying enzymes Carboxyl esterase (Car E) and Glutathione S - transferases (GST).

}, issn = {1614-7499}, doi = {10.1007/s11356-021-14282-x}, author = {Senthoorraja, Rajendran and Subaharan, Kesavan and Manjunath, Sowmya and Pragadheesh, Vppalayam Shanmugam and Bakthavatsalam, Nandagopal and Mohan, Muthu Gounder and Senthil-Nathan, Sengottayan and Basavarajappa, Sekarappa} } @article {90472, title = {Emerging cell biological functions of phosphatidylinositol 5 phosphate 4 kinase.}, journal = {Curr Opin Cell Biol}, volume = {71}, year = {2021}, month = {2021 Mar 04}, pages = {15-20}, abstract = {

The generation of phosphoinositides (PIs) with spatial and temporal control is a key mechanism in cellular organization and signaling. The synthesis of PIs is mediated by PI kinases, proteins that are able to phosphorylate unique substrates at specific positions on the inositol headgroup to generate signaling molecules. Phosphatidylinositol 5 phosphate 4 kinase (PIP4K) is one such lipid kinase that is able to specifically phosphorylate phosphatidylinositol 5 phosphate, the most recently discovered PI to generate the well-known and abundant PI, phosphatidylinositol 4,5 bisphosphate [PI(4,5)P]. PIP4K appears to be encoded only in metazoan genomes, and several genetic studies indicate important physiological functions for these enzymes in metabolism, immune function, and growth control. PIP4K has recently been reported to localize to multiple cellular compartments, including the nucleus, plasma membrane, endosomal systems, and autophagosome. However, the biochemical activity of these enzymes that is relevant to these physiological functions remains elusive. We review recent developments in this area and highlight emerging roles for these enzymes in cellular organization.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2021.01.012}, author = {Raghu, Padinjat} } @article {94390, title = {Emerging perspectives on multidomain phosphatidylinositol transfer proteins.}, journal = {Biochim Biophys Acta Mol Cell Biol Lipids}, year = {2021}, month = {2021 Jun 04}, pages = {158984}, abstract = {

The phosphatidylinositol transfer protein domain (PITP) is an evolutionarily conserved protein that is able to transfer phosphatidylinositol between membranes in vitro and in vivo. However some animal genomes also include genes that encode proteins where the PITP is found in cis with a number of additional domains and recent large scale genome sequencing efforts indicate that this type of multidomain architecture is widespread in the animal kingdom. In Drosophila photoreceptors, the multidomain phosphatidylinositol transfer protein RDGB is required to regulate phosphoinositide turnover during G-protein activated phospholipase C signalling. Recent studies in flies and mammalian cell culture models have begun to elucidate functions for the non-PITP of RDGB and its vertebrate orthologs. We review emerging evidence on the genomics, functional and cell biological perspectives of these multi-domain PITP containing proteins.

}, issn = {1879-2618}, doi = {10.1016/j.bbalip.2021.158984}, author = {Raghu, Padinjat and Basak, Bishal and Krishnan, Harini} } @article {100194, title = {Engineered RNA biosensors enable ultrasensitive SARS-CoV-2 detection in a simple color and luminescence assay.}, journal = {Life Sci Alliance}, volume = {4}, year = {2021}, month = {2021 Dec}, abstract = {

The continued resurgence of the COVID-19 pandemic with multiple variants underlines the need for diagnostics that are adaptable to the virus. We have developed toehold RNA-based sensors across the SARS-CoV-2 genome for direct and ultrasensitive detection of the virus and its prominent variants. Here, isothermal amplification of a fragment of SARS-CoV-2 RNA coupled with activation of our biosensors leads to a conformational switch in the sensor. This leads to translation of a reporter protein, for example, LacZ or nano-lantern that is easily detected using color/luminescence. By optimizing RNA amplification and biosensor design, we have generated a highly sensitive diagnostic assay that is capable of detecting as low as 100 copies of viral RNA with development of bright color. This is easily visualized by the human eye and quantifiable using spectrophotometry. Finally, this PHAsed NASBA-Translation Optical Method (PHANTOM) using our engineered RNA biosensors efficiently detects viral RNA in patient samples. This work presents a powerful and universally accessible strategy for detecting COVID-19 and variants. This strategy is adaptable to further viral evolution and brings RNA bioengineering center-stage.

}, issn = {2575-1077}, doi = {10.26508/lsa.202101213}, author = {Chakravarthy, Anirudh and Nandakumar, Anirudh and George, Geen and Ranganathan, Shyamsundar and Umashankar, Suchitta and Shettigar, Nishan and Palakodeti, Dasaradhi and Gulyani, Akash and Ramesh, Arati} } @article {86472, title = {Epidemiological and ES cell-based Functional Evaluation of BRCA2 Variants Identified in Families with Breast Cancer.}, journal = {Hum Mutat}, volume = {42}, year = {2021}, month = {2020 Dec 13}, pages = {200-212}, chapter = {2}, abstract = {

The discovery of high-risk breast cancer susceptibility genes such as BRCA1 DNA Repair Associated (BRCA1) and BRCA2 DNA Repair Associated (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations. Here we report the characterization of novel variants in the Malaysian and Singaporean population that consist of different ethnic groups (Malays, Chinese, Indian and other indigenous groups). We have evaluated the functional significance of 14 BRCA2 VUS by using multiple in silico prediction tools and examined their frequency in a cohort of 7,840 breast cancer cases and 7,928 healthy controls. In addition, we have used a mouse embryonic stem cell (mESC)-based functional assay to assess the impact of these variants on BRCA2 function. We found these variants to be functionally indistinguishable from wild-type BRCA2. These variants could fully rescue the lethality of Brca2-null mESCs and exhibited no sensitivity to six different DNA damaging agents including a PARP inhibitor. Our findings strongly suggest that all 14 evaluated variants are functionally neutral. Our findings should be valuable in risk assessment of individuals carrying these variants. This article is protected by copyright. All rights reserved.

}, issn = {1098-1004}, doi = {10.1002/humu.24154}, author = {Sullivan, Teresa and Thirthagiri, Eswary and Chong, Chan-Eng and Stauffer, Stacey and Reid, Susan and Southon, Eileen and Hassan, Tiara and Ravichandran, Aravind and Wijaya, Eldarina and Lim, Joanna and Taib, Nur Aishah Mohd and Fadzli, Farhana and Yip, Cheng Har and Hartman, Mikael and Li, Jingmei and van Dam, Rob M and North, Susan L and Das, Ranabir and Easton, Douglas F and Biswas, Kajal and Teo, Soo-Hwang and Sharan, Shyam K} } @article {99103, title = {Essential role of γ-clade RNA-dependent RNA polymerases in rice development and yield-related traits is linked to their atypical polymerase activities regulating specific genomic regions.}, journal = {New Phytol}, year = {2021}, month = {2021 Aug 27}, abstract = {

RNA-dependent RNA polymerases (RDR) generate double-stranded (ds)RNA triggers for RNA silencing across eukaryotes. Among the three clades, α- and β-clade members are key components of RNA silencing and mediators of stress responses across eukaryotes. However, γ-clade members are unusual in that they are represented in phylogenetically distant plants and fungi, and their functions are unknown. Using genetic, bioinformatic and biochemical methods, we show that γ-clade RDRs from Oryza sativa L. are involved in plant development as well as regulation of expression of coding and non-coding RNAs. Overexpression of γ-clade RDRs in transgenic rice and tobacco plants resulted in robust growth phenotype, whereas their silencing in rice displayed strong inhibition of growth. Small (s)RNA and RNA-seq analysis of OsRDR3 mis-expression lines suggested that it is specifically involved in the regulation of repeat-rich regions in the genome. Biochemical analysis confirmed that OsRDR3 has robust polymerase activities on both single stranded (ss)RNA and ssDNA templates similar to the activities reported for α-clade RDRs such as AtRDR6. Our results provide the first evidence of the importance of γ-clade RDRs in plant development, their atypical biochemical activities, and their contribution to the regulation of gene expression.

}, issn = {1469-8137}, doi = {10.1111/nph.17700}, author = {Jha, Vikram and Narjala, Anushree and Basu, Debjani and Sujith, T N and Pachamuthu, Kannan and Chenna, Swetha and Nair, Ashwin and Shivaprasad, Padubidri V} } @article {88401, title = {Evidence for facultative migratory flight behavior in Helicoverpa armigera (Noctuidae: Lepidoptera) in India.}, journal = {PLoS One}, volume = {16}, year = {2021}, month = {2021}, pages = {e0245665}, abstract = {

Despite its deleterious impact on farming and agriculture, the physiology and energetics of insect migration is poorly understood due to our inability to track their individual movements in the field. Many insects, e.g. monarch butterflies, Danaus plexippus (L.), are facultative migrants. Hence, it is important to establish whether specific insect populations in particular areas migrate. The polyphagous insect, Helicoverpa armigera (H{\"u}bner), is especially interesting in this regard due to its impact on a variety of crops. Here, we used a laboratory-based flight mill assay to show that Helicoverpa armigera populations clearly demonstrate facultative migration in South India. Based on various flight parameters, we categorized male and female moths as long, medium or short distance fliers. A significant proportion of moths exhibited long-distance flight behavior covering more than 10 km in a single night, averaging about 8 flight hours constituting 61\% flight time in the test period. The maximum and average flight speeds of these long fliers were greater than in the other categories. Flight activity across sexes also varied; male moths exhibited better performance than female moths. Wing morphometric parameters including forewing length, wing loading, and wing aspect ratio were key in influencing long-distance flight. Whereas forewing length positively correlated with flight distance and duration, wing loading was negatively correlated.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0245665}, author = {Jyothi, Patil and Aralimarad, Prabhuraj and Wali, Vijaya and Dave, Shivansh and Bheemanna, M and Ashoka, J and Shivayogiyappa, Patil and Lim, Ka S and Chapman, Jason W and Sane, Sanjay P} } @inbook {103400, title = {Evolution of Mimicry Rings as a Window into Community Dynamics}, booktitle = {ANNUAL REVIEW OF ECOLOGY EVOLUTION AND SYSTEMATICS }, volume = {52}, year = {2021}, pages = {315-341}, abstract = {

Mimicry rings are communities of mimetic organisms that are excellent models for ecological and evolutionary studies because the community composition, the nature of the species interactions, the phenotypes under selection, and the selective agents are well characterized. Here, we review how regional and ecological filtering, density- and frequency-dependent selection, toxicity of prey, and age of mimicry rings shape their assembly. We synthesize findings from theoretical and empirical studies to generate the following hypotheses: (a) the degree of unpalatability and age of mimicry rings increase mimicry ring size and (b) the degree of unpalatability, generalization of the aposematic signal, and availability of alternative prey are positively related to the breadth of the protection umbrella for an aposematic signal and negatively related to the degree of mimetic resemblance. We also provide a phylogenetic framework in which key aspects of mimicry ring diversification may be studied.

}, issn = {eISSN 1545-2069}, doi = {10.1146/annurev-ecolsys-012021-024616}, author = {Kunte, Krushnamegh and Kizhakke, Athulya Girish and Nawge, Viraj and Futuyma, DJ} } @article {87969, title = {Evolutionarily related small viral fusogens hijack distinct but modular actin nucleation pathways to drive cell-cell fusion.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Jan 05}, abstract = {

Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP-mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.

}, issn = {1091-6490}, doi = {10.1073/pnas.2007526118}, author = {Chan, Ka Man Carmen and Arthur, Ashley L and Morstein, Johannes and Jin, Meiyan and Bhat, Abrar and Schlesinger, D{\"o}rte and Son, Sungmin and Stevens, Dont{\'e} A and Drubin, David G and Fletcher, Daniel A} } @article {86448, title = {Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer}, journal = {Oncogene}, volume = {40}, year = {2021}, month = {12/2020}, pages = {863-874}, chapter = {40}, abstract = {

Early-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole-exome sequencing of 47 microsatellite stable EOSRC samples. Signature 1 was the predominant mutational signature in EOSRC, as previously shown in other CRC exome studies. More importantly, we identified TP53, KRAS, APC, PIK3R1, SMAD4 and ZNF880 as significantly mutated (q \< 0.1) and ARID1A and ARID2 as near-significantly mutated (restricted hypothesis testing; q \< 0.1) candidate drivers. Unlike the other candidates, the tumorigenic potential of ARID2, encoding a component of the SWI/SNF chromatin remodeling complex, is largely unexplored in CRC. shRNA-mediated ARID2 knockdown performed in different CRC cell lines resulted in significant alterations in transcript levels of cancer-related target genes. More importantly, ARID2 knockdown promoted several tumorigenic features including cell viability, proliferation, ability to override contact inhibition of growth, and migration besides significantly increasing tumor formation ability in nude mice. The observed gain in tumorigenic features was rescued upon ectopic expression of wild type but not mutant ARID2. Analyses of the TCGA pan-cancer dataset revealed several modes of ARID2 inactivation and of the CRC dataset revealed poorer survival in patients with ARID2 alterations. We therefore propose ARID2 as a novel tumor suppressor in CRC.

}, doi = {10.1038/s41388-020-01537-z}, author = {Bala, P and Singh, AK and Kavadipula, P and Kotapalli, V and Sabarinathan, R and Bashyam, MD.} } @article {91136, title = {Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes.}, journal = {Cell Death Dis}, volume = {12}, year = {2021}, month = {2021 Mar 11}, pages = {259}, abstract = {

Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein-Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (

}, issn = {2041-4889}, doi = {10.1038/s41419-021-03542-w}, author = {Dalal, Hamza and Subramanian, Sitalakshmi and V P, Snijesh and Gowda, Divya A and H, Krishnamurthy and Damodar, Sharat and Vyas, Neha} } @article {93665, title = {Expanding capabilities and infrastructure for cryo-EM.}, journal = {Nat Methods}, volume = {18}, year = {2021}, month = {2021 May}, pages = {437-438}, issn = {1548-7105}, doi = {10.1038/s41592-021-01139-x}, author = {Vinothkumar, Kutti R} } @article {98079, title = {Expansion of pine into mid-elevation Himalayan oak forests: Patterns and drivers in a multiple-use landscape}, journal = {Forest Ecology And Management}, volume = {119491}, year = {2021}, month = {10/2021}, abstract = {

Oak species worldwide are experiencing declines, with negative consequences for hardwood forests and their associated biodiversity, but the causes of these declines vary across species and habitats. We examine changes in extent of banj oak-dominated (Quercus leucotrichophora) moist temperate hardwood forests in a Western Hi-malayan landscape between 1991 and 2017. Using classified satellite imagery from 1991, 2001 and 2017, we found that dense banj oak forests have undergone substantial degradation and loss of area, while chir pine (Pinus roxburghii) forests have expanded, largely by replacing degraded banj oak stands. This transition was most likely to occur at sites that had lower levels of winter precipitation and Topographic Wetness Index (TWI) values and more pine forest in the surrounding landscape. Our findings are consistent with known requirements of shade and moisture for the recruitment of banj oak. Loss of banj oak forests is likely to reduce biodiversity and a number of ecosystem services linked to the well-being of local communities.

}, doi = {10.1016/j.foreco.2021.119491}, author = {Das, Arundhati and Menon, Tarun and Ratnam, Jayashree and Thadani, Rajesh and Rajashekar, Gopalakrishnan and Fararoda, Rakesh and Shahabuddin, Ghazala} } @article {99334, title = {Expansion~of the evolutionarily conserved network of J-domain proteins in the Arabidopsis mitochondrial import complex.}, journal = {Plant Mol Biol}, volume = {105}, year = {2021}, month = {2021 Mar}, pages = {385-403}, abstract = {

KEY MESSAGE: We report that discriminate interaction between the expanded mitochondrial chaperone network and variability in their expression might determine their functional specificities and impart robustness to mitochondrial import processes in plants. Mitochondrial Hsp70 (mtHsp70), the central component of the pre-sequence associated motor (PAM) complex, is crucial for the import of proteins to the mitochondrial matrix. Activity of mtHsp70 is regulated by a heterodimeric complex of two J-domain proteins (JDPs), Pam18 and Pam16. Compared to other eukaryotes, plants harbor multiple copies of these JDPs, which posit that plants have an increasingly complex mtHsp70: JDP\ network in their mitochondrial matrix. Here, we show that although highly similar in sequence, some of the plant JDPs are functionally different. Protein: protein interaction studies including yeast two-hybrid and Bimolecular Fluorescence Complementation revealed that while all the AtPam18s interacted with AtPam16s, the strengths of these promiscuous interactions are variable. Further, down-regulation of\ AtPAM16L affected seed germination, even in the presence of its seemingly identical paralog, AtPAM16. Knockdown of\ AtPAM16L caused reduction in mitochondrial number and deregulation of several mitochondrial genes, suggesting towards a specific role of\ AtPam16L in maintaining mitochondrial homeostasis, especially under stress conditions. Our findings suggest that variations in the spatio-temporal expression, accompanied by discriminate interactions between the JDPs, might be defining the functional specificity of the mtHsp70 co-chaperone machinery and providing resilience to mitochondrial import processes in plants, especially under stress conditions.

}, keywords = {Arabidopsis, Arabidopsis Proteins, Gene Expression Regulation, Developmental, Gene Expression Regulation, Plant, HSP70 Heat-Shock Proteins, Mitochondria, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Mutation, Plants, Genetically Modified, Protein Binding, Protein Domains, Protein Transport}, issn = {1573-5028}, doi = {10.1007/s11103-020-01095-8}, author = {Tamadaddi, Chetana and Sagar, Vinay and Verma, Amit K and Afsal, Fathima and Sahi, Chandan} } @article {101429, title = {Experiential modulation of social dominance in a SYNGAP1 rat model of ASD.}, journal = {Eur J Neurosci}, year = {2021}, month = {2021 Oct 20}, abstract = {

Advances in the understanding of developmental brain disorders such as autism spectrum disorders (ASD) is being achieved through human neurogenetics such as, for example, identifying de novo mutations in SYNGAP1 as one relatively common cause of ASD. A recently developed rat line lacking the calcium/lipid binding (C2) and GTPase activation protein (GAP) domain may further help uncover the neurobiological basis of deficits in children with ASD. This study focused on social dominance in the tube test using Syngap (rats heterozygous for the C2/GAP domain deletion) as alterations in social behaviour are a key facet of the human phenotype. Male animals of this line living together formed a stable intra-cage hierarchy, but they were submissive when living with WT cage-mates thereby modelling the social withdrawal seen in ASD. The study includes a detailed analysis of specific behaviours expressed in social interactions by WT and mutant animals, including the observation that when the Syngap mutants which had been living together had separate dominance encounters with WT animals from other cages, the two higher ranking Syngap rats remained dominant whereas the two lower ranking mutants were still submissive. While only observed in a small subset of animals, these findings support earlier observations with a rat model of Fragile-X indicating that their experience of winning or losing dominance encounters has a lasting influence on subsequent encounters with others. Our results highlight and model that even with single-gene mutations, dominance phenotypes reflect an interaction between genotypic and environmental factors.

}, issn = {1460-9568}, doi = {10.1111/ejn.15500}, author = {Harris, E and Myers, H and Saxena, K and Mitchell-Heggs, R and Kind, P and Chattarji, S and Morris, R G M} } @article {91466, title = {Field evaluation of PGP Bacillus sp. strain D5 native to Crocus sativus, in traditional and non traditional areas, and mining of PGP genes from its genome.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 Mar 09}, pages = {5454}, abstract = {

Native Bacillus sp. strain D5 coded as (Bar D5) has been isolated from the saffron corm that showed plant growth promotion (PGP) properties and also inhibits the growth of corm rot causing Fusarium oxysporum R1 (Fox R1) in-vitro. Bar D5 was more efficient PGP bacterium in comparison to earlier reported native bio-formulations by our group. Pot assays and field evaluation of Bar D5 confirmed its in-vivo efficacy for PGP traits and biocontrol activity as well. Pot trials were followed by field trials at traditional (Kishtwar) and non-traditional (R.S Pura) saffron cultivation areas in Jammu and Kashmir. At both places, Bar D5 bio-formulation treatment led to the increase in root number \& length, shoot number \& length, flower number and number \& weight of daughter corms. Additionally, it also decreased the corm rot disease incidence significantly. Priming of corms with bio-formulation resulted in the reduction of pathogenic fungal load by three\ fold at the depth of corm sowing from ground level. The shelf life/viability of Bar D5 based bio-formulation was found to be 52\% (viable spores) for one year at room temperature. Draft genome sequence of Bar D5 revealed the presence of genes necessary for PGP and biocontrol activity. Further, confirmation of gene sequences and annotation was done by amplification, re-sequencing and mapping of PGP and biocontrol genes on draft genome. Bar D5 based bio-formulation can be provided to companies/researchers interested in saffron cultivation or bio-formulation production for commercial exploitation, since saffron is grown as revenue crop across continents. The present study bridges the gap between genomics and its field application.

}, issn = {2045-2322}, doi = {10.1038/s41598-021-84585-z}, author = {Magotra, Shanu and Bhagat, Nancy and Ambardar, Sheetal and Ali, Tahir and Hurek, Barbara Reinhold and Hurek, Thomas and Verma, Praveen Kumar and Vakhlu, Jyoti} } @article {101903, title = {Flock-species richness influences node importance and modularity in mixed-species flock networks.}, journal = {Oecologia}, year = {2021}, month = {2021 Oct 28}, abstract = {

Interdependencies in social groups of animals are a combination of multiple pairwise interactions. Heterospecific groups are often characterized by important species that contribute more to group initiation, maintenance or function than other species. However, in large heterospecific groups, many pairwise interactions are not realised, while others may not be biologically significant, confounding inferences about species importance. Hence, in this study, we examine context dependent changes in species importance and assortment in mixed-species bird flocks from a tropical field site in Southern India using social network analysis. Specifically, we ask how the structural importance of a species and the clustering patterns of species relationships depends on species richness in mixed-species flocks. We constructed both raw and filtered networks; while our results are largely correlated, we believe that filtered networks can provide insights into community-level importance of species in mixed-flocks while raw networks depict flock-level patterns. We find significant differences in flocks of different richness in that different species emerge as structurally important across flocks of varying richness. We also find that assortment is higher in two-species flocks and decreases with\ an increase in the number of species in the flock ({\textquoteright}flock richness{\textquoteright} hereafter). We argue that the link between structural importance of species in mixed-species flock networks and their functional significance in the community critically depends on the social context: namely, the species richness of the mixed-species flock. We propose that examining species structural importance at different flock-richness values provides insights into biologically meaningful functional roles of species. More generally, we suggest that it is important to consider context when interpreting species centrality and importance in network structure.

}, issn = {1432-1939}, doi = {10.1007/s00442-021-05053-z}, author = {Bangal, Priti and Sridhar, Hari and Shizuka, Daizaburo and Vander Meiden, Laura N and Shanker, Kartik} } @article {91674, title = {Formin nanoclustering-mediated actin assembly during plant flagellin and DSF signaling.}, journal = {Cell Rep}, volume = {34}, year = {2021}, month = {2021 Mar 30}, pages = {108884}, abstract = {

Plants respond to bacterial infection acutely with actin remodeling during plant immune responses. The mechanisms by which bacterial virulence factors (VFs) modulate plant actin polymerization remain enigmatic. Here, we show that plant-type-I formin serves as the molecular sensor for actin remodeling in response to two bacterial VFs: Xanthomonas campestris pv. campestris (Xcc) diffusible signal factor (DSF), and pathogen-associated molecular pattern (PAMP) flagellin in pattern-triggered immunity (PTI). Both VFs regulate actin assembly by tuning the clustering and nucleation activity of formin on the plasma membrane (PM) at the nano-sized scale. By being integrated within the cell-wall-PM-actin cytoskeleton (CW-PM-AC) continuum, the dynamic behavior and function of formins are highly dependent on each scaffold layer{\textquoteright}s composition within the CW-PM-AC continuum during both DSF and PTI signaling. Our results reveal a central mechanism for rapid actin remodeling during plant-bacteria interactions, in which bacterial signaling molecules fine tune plant formin nanoclustering in a host mechanical-structure-dependent manner.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2021.108884}, author = {Ma, Zhiming and Liu, Xiaolin and Nath, Sangeeta and Sun, He and Tran, Tuan Minh and Yang, Liang and Mayor, Satyajit and Miao, Yansong} } @article {102045, title = {A Framework for Stochastic Optimization of Parameters for Integrative Modeling of Macromolecular Assemblies}, journal = {Life}, volume = {11}, year = {2021}, month = {11/2021}, pages = {1183}, abstract = {

ntegrative modeling of macromolecular assemblies requires stochastic sampling, for example, via MCMC (Markov Chain Monte Carlo), since exhaustively enumerating all structural degrees of freedom is infeasible. MCMC-based methods usually require tuning several parameters, such as the move sizes for coarse-grained beads and rigid bodies, for sampling to be efficient and accurate. Currently, these parameters are tuned manually. To automate this process, we developed a general heuristic for derivative-free, global, stochastic, parallel, multiobjective optimization, termed StOP (Stochastic Optimization of Parameters) and applied it to optimize sampling-related parameters for the Integrative Modeling Platform (IMP). Given an integrative modeling setup, list of parameters to optimize, their domains, metrics that they influence, and the target ranges of these metrics, StOP produces the optimal values of these parameters. StOP is adaptable to the available computing capacity and converges quickly, allowing for the simultaneous optimization of a large number of parameters. However, it is not efficient at high dimensions and not guaranteed to find optima in complex landscapes. We demonstrate its performance on several examples of random functions, as well as on two integrative modeling examples, showing that StOP enhances the efficiency of sampling the posterior distribution, resulting in more good-scoring models and better sampling precision

}, doi = {10.3390/life11111183}, author = {Pasani, Satwik and Viswanath, Shruthi} } @article {82441, title = {Functional characterization of a defense-responsive bulnesol/elemol synthase from potato.}, journal = {Physiol Plant}, volume = {171}, year = {2021}, month = {2020 Sep 03}, pages = {7-21}, abstract = {

Terpene synthases (TPSs) produce a variety of terpenoids that play numerous functional roles in primary and secondary metabolism, as well as in ecological interactions. Here, we report the functional characterization of an inducible potato TPS gene encoding bulnesol/elemol synthase (StBUS/ELS). The expression of StBUS/ELS in potato leaves was significantly induced in response to both bacterial (Pseudomonas syringae) and fungal (Alternaria solani) infection as well as methyl jasmonate treatment, indicating its role in defense. The leaves exhibited the highest StBUS/ELS expression followed by the stem with least and similar expression in tuber, sprout and root. Recombinant StBUS/ELS catalyzed the formation of different sesquiterpenes by utilizing farnesyl diphosphate as substrate, and the monoterpene geraniol from geranyl diphosphate. Among the sesquiterpenes formed by StBUS/ELS, elemol was the predominant product followed by α-bulnesene, bulnesol, and β-elemene. Further GC-MS analysis of StBUS/ELS assay products at different injection temperatures revealed elemol and bulnesol as the major products at 275{\textdegree}C and 200/150{\textdegree}C, respectively, without much change in the levels of minor products. This indicated thermal rearrangement of bulnesol into elemol at higher temperatures. Transient overexpression of StBUS/ELS in potato leaves conferred tolerance against the growth of bacteria P. syringae and Ralstonia solanacearum, and the fungus A. solani. Further, expression analysis of pathogenesis-related (PR) genes in StBUS/ELS overexpressing leaves showed no significant change in comparison to control, indicating a direct involvement of StBUS/ELS enzymatic products against pathogens. Overall, our study suggested that StBUS/ELS is a pathogen-inducible TPS encoding bulnesol/elemol synthase and could provide a direct role in defense against biotic stress in potato.

}, issn = {1399-3054}, doi = {10.1111/ppl.13199}, author = {Dwivedi, Varun and Rao, Srinivas and Bomzan, Dikki Pedenla and Kumar, Sarma Rajeev and Shanmugam, Pragadheesh V and Olsson, Shannon B and Nagegowda, Dinesh A} } @article {95775, title = {Functional traits predict tree-level phenological strategies in a mesic Indian savanna}, journal = {BIOTROPICA}, year = {2021}, month = {06/2021}, abstract = {

Leaf phenology influences terrestrial primary production by determining the period of carbon uptake. While dominant leaf habit (evergreen/deciduous) is predictable at large scales based on environmental factors, there is substantial variability in the timing of key events such as leaf flush and senescence at smaller site-level scales. How much of this variability is explained by species functional traits related to a plant{\textquoteright}s carbon economy? We monitored leaf phenology for 113 individual trees of eleven dominant species in an Indian mesic savanna. Specifically, we related leaf functional traits and wood density to the (i) timing of leaf flush, leaf maturity, peak canopy, and senescence, (ii) duration of leaf deployment, (iii) duration from start of senescence to leaflessness, and (iv) time to attainment of peak mature canopy following leaf flush. We expected species that use resources conservatively (low specific leaf area (SLA), high leaf dry matter content, low leaf nitrogen, and high wood density) to senesce later and retain their leaves longer. For all species, leaflessness was most pronounced in early dry season and leaf flushing occurred in the late dry season. Species with high leaf carbon and dry matter content showed earlier leaf maturation, attained peak mature canopies sooner, and deployed leaves longer. Species with high SLA, leaf nitrogen, and low wood density showed earlier senescence but relationships were weak. In this savanna, phenology at fine scales was indeed associated with species functional traits relating to carbon investment, but these relationships were strong only when intra-specific variation in phenology was low.

}, doi = {10.1111/btp.12993}, author = {Ongole, Shasank and Teegalapalli, Karthik and Byrapoghu, Venkateshwarlu and Ratnam, Jayashree and Sankaran, Mahesh} } @article {92223, title = {Genome-wide survey of tyrosine phosphatases in thirty mammalian genomes}, journal = {Cell Signal}, year = {2021}, month = {04/2021}, abstract = {

The age of genomics has given us a wealth of information and the tools to study whole genomes. This, in turn, has facilitated genome-wide studies among organisms that were relatively less studied in the pre-genomic era or are non-model organisms. This paves the way to the discovery of interesting evolutionary patterns, which are brought to light by genome-wide surveys of protein superfamilies. Phosphorylation is a post-translational modification that is utilised across all clades of life, and acts as an important signalling switch, regulating several cellular processes. Tyrosine phosphatases, which are found predominantly in eukaryotes, act on phosphorylated tyrosine residues and sometimes on other substrates. Extending on our previous effort to look for tyrosine phosphatases in the human genome, we have looked for sequences of the cysteine-based tyrosine phosphatase superfamily in thirty mammalian genomes from all across Mammalia and validated the sequences with the presence of the signature catalytic motif. Domain architecture annotation, followed by in-depth analysis, revealed interesting taxon-specific patterns such as subtle differences between the protein families in marsupials and early mammals versus placental mammals. Finally, we discuss an interesting case of loss of the tyrosine phosphatase domain from a gene product in the course of eutherian evolution

}, doi = {10.1016/j.cellsig.2021.110009}, author = {Bhattacharyya, Teerna and Sowdhamini, Ramanathan} } @article {103406, title = {Genomic evidence for inbreeding depression and purging of deleterious genetic variation in Indian tigers.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Dec 07}, abstract = {

Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used whole-genome sequences from 57 tigers to estimate individual inbreeding and mutation load in a small-isolated and two large-connected populations in India. As expected, the small-isolated population had substantially higher average genomic inbreeding ( = 0.57) than the large-connected ( = 0.35 and = 0.46) populations. The small-isolated population had the lowest loss-of-function mutation load, likely due to purging of highly deleterious recessive mutations. The large populations had lower missense mutation loads than the small-isolated population, but were not identical, possibly due to different demographic histories. While the number of the loss-of-function alleles in the small-isolated population was lower, these alleles were at higher frequencies and homozygosity than in the large populations. Together, our data and analyses provide evidence of 1) high mutation load, 2) purging, and 3) the highest predicted inbreeding depression, despite purging, in the small-isolated population. Frequency distributions of damaging and neutral alleles uncover genomic evidence that purifying selection has removed part of the mutation load across Indian tiger populations. These results provide genomic evidence for purifying selection in both small and large populations, but also suggest that the remaining deleterious alleles may have inbreeding-associated fitness costs. We suggest that genetic rescue from sources selected based on genome-wide differentiation could offset any possible impacts of inbreeding depression.

}, issn = {1091-6490}, doi = {10.1073/pnas.2023018118}, author = {Khan, Anubhab and Patel, Kaushalkumar and Shukla, Harsh and Viswanathan, Ashwin and van der Valk, Tom and Borthakur, Udayan and Nigam, Parag and Zachariah, Arun and Jhala, Yadavendradev V and Kardos, Marty and Ramakrishnan, Uma} } @article {103921, title = {A geometric criterion for the optimal spreading of active polymers in porous media.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 Dec 06}, pages = {7088}, abstract = {

Efficient navigation through disordered, porous environments poses a major challenge for swimming microorganisms and future synthetic cargo-carriers. We perform Brownian dynamics simulations of active stiff polymers undergoing run-reverse dynamics, and so mimic bacterial swimming, in porous media. In accord with experiments of Escherichia coli, the polymer dynamics are characterized by trapping phases interrupted by directed hopping motion through the pores. Our findings show that the spreading of active agents in porous media can be optimized by tuning their run lengths, which we rationalize using a coarse-grained model. More significantly, we discover a geometric criterion for the optimal spreading, which emerges when their run lengths are comparable to the longest straight path available in the porous medium. Our criterion unifies results for porous media with disparate pore sizes and shapes and for run-and-tumble polymers. It thus provides a fundamental principle for optimal transport of active agents in densely-packed biological and environmental settings.

}, issn = {2041-1723}, doi = {10.1038/s41467-021-26942-0}, author = {Kurzthaler, Christina and Mandal, Suvendu and Bhattacharjee, Tapomoy and L{\"o}wen, Hartmut and Datta, Sujit S and Stone, Howard A} } @article {99112, title = {Geometry of gene regulatory dynamics.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Sep 21}, abstract = {

Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different cell types that elaborate this complexity results from the activity of gene networks and was likened by Waddington to a flow through a landscape in which valleys represent alternative fates. Geometric methods allow the formal representation of such landscapes and codify the types of behaviors that result from systems of differential equations. Results from Smale and coworkers imply that systems encompassing gene network models can be represented as potential gradients with a Riemann metric, justifying the Waddington metaphor. Here, we extend this representation to include parameter dependence and enumerate all three-way cellular decisions realizable by tuning at most two parameters, which can be generalized to include spatial coordinates in a tissue. All diagrams of cell states vs. model parameters are thereby enumerated. We unify a number of standard models for spatial pattern formation by expressing them in potential form (i.e., as topographic elevation). Turing systems appear nonpotential, yet in suitable variables the dynamics are low dimensional and potential. A time-independent embedding recovers the original variables. Lateral inhibition is described by a saddle point with many unstable directions. A model for the patterning of the eye appears as relaxation in a bistable potential. Geometric reasoning provides intuitive dynamic models for development that are well adapted to fit time-lapse data.

}, issn = {1091-6490}, doi = {10.1073/pnas.2109729118}, author = {Rand, David A and Raju, Archishman and S{\'a}ez, Meritxell and Corson, Francis and Siggia, Eric D} } @article {97224, title = {Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Aug 04}, abstract = {

Gap junctions between neurons serve as electrical synapses, in addition to conducting metabolites and signaling molecules. During development, early-appearing gap junctions are thought to prefigure chemical synapses, which appear much later. We present evidence for this idea at a central, glutamatergic synapse and provide some mechanistic insights. Loss or reduction in the levels of the gap junction protein Gjd2b decreased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cerebellar Purkinje neurons (PNs) in larval zebrafish. Ultrastructural analysis in the molecular layer showed decreased synapse density. Further, mEPSCs had faster kinetics and larger amplitudes in mutant PNs, consistent with their stunted dendritic arbors. Time-lapse microscopy in wild type and mutant PNs reveals that Gjd2b puncta promote the elongation of branches and that CaMKII may be a critical mediator of this process. These results demonstrate that Gjd2b-mediated gap junctions regulate glutamatergic synapse formation and dendritic elaboration in PNs.

}, issn = {2050-084X}, doi = {10.7554/eLife.68124}, author = {Sitaraman, Sahana and Yadav, Gnaneshwar and Agarwal, Vandana and Jabeen, Shaista and Verma, Shivangi and Jadhav, Meha and Thirumalai, Vatsala} } @article {99107, title = {Global Commitments to Conserving and Monitoring Genetic Diversity Are Now Necessary and Feasible.}, journal = {Bioscience}, volume = {71}, year = {2021}, month = {2021 Sep}, pages = {964-976}, abstract = {

Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species{\textquoteright} adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.

}, issn = {0006-3568}, doi = {10.1093/biosci/biab054}, author = {Hoban, Sean and Bruford, Michael W and Funk, W Chris and Galbusera, Peter and Griffith, M Patrick and Grueber, Catherine E and Heuertz, Myriam and Hunter, Margaret E and Hvilsom, Christina and Stroil, Belma Kalamujic and Kershaw, Francine and Khoury, Colin K and Laikre, Linda and Lopes-Fernandes, Margarida and MacDonald, Anna J and Mergeay, Joachim and Meek, Mariah and Mittan, Cinnamon and Mukassabi, Tarek A and O{\textquoteright}Brien, David and Ogden, Rob and Palma-Silva, Clarisse and Ramakrishnan, Uma and Segelbacher, Gernot and Shaw, Robyn E and Sj{\"o}gren-Gulve, Per and Veli{\v c}kovi{\'c}, Nevena and Vernesi, Cristiano} } @article {94676, title = {A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions.}, journal = {Sci Total Environ}, volume = {788}, year = {2021}, month = {2021 Sep 20}, pages = {147868}, abstract = {

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium- and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a {\textquoteright}very high risk{\textquoteright} of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate {\textquoteright}rapid{\textquoteright} management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2021.147868}, author = {Vilizzi, Lorenzo and Copp, Gordon H and Hill, Jeffrey E and Adamovich, Boris and Aislabie, Luke and Akin, Daniel and Al-Faisal, Abbas J and Almeida, David and Azmai, M N Amal and Bakiu, Rigers and Bellati, Adriana and Bernier, Ren{\'e}e and Bies, Jason M and Bilge, G{\"o}k{\c c}en and Branco, Paulo and Bui, Thuyet D and Canning-Clode, Jo{\~a}o and Cardoso Ramos, Henrique Anatole and Castellanos-Galindo, Gustavo A and Castro, Nuno and Chaichana, Ratcha and Chainho, Paula and Chan, Joleen and Cunico, Almir M and Curd, Amelia and Dangchana, Punyanuch and Dashinov, Dimitriy and Davison, Phil I and de Camargo, Mariele P and Dodd, Jennifer A and Durland Donahou, Allison L and Edsman, Lennart and Ekmek{\c c}i, F G{\"u}ler and Elphinstone-Davis, Jessica and Er{\H o}s, Tibor and Evangelista, Charlotte and Fenwick, Gemma and Ferincz, {\'A}rp{\'a}d and Ferreira, Teresa and Feunteun, Eric and Filiz, Halit and Forneck, Sandra C and Gajduchenko, Helen S and Gama Monteiro, Jo{\~a}o and Gestoso, Ignacio and Giannetto, Daniela and Gilles, Allan S and Gizzi, Francesca and Glamuzina, Branko and Glamuzina, Luka and Goldsmit, Jesica and Gollasch, Stephan and Goulletquer, Philippe and Grabowska, Joanna and Harmer, Rogan and Haubrock, Phillip J and He, Dekui and Hean, Jeffrey W and Herczeg, G{\'a}bor and Howland, Kimberly L and {\.I}lhan, Ali and Interesova, Elena and Jakub{\v c}inov{\'a}, Katar{\'\i}na and Jelmert, Anders and Johnsen, Stein I and Kakareko, Tomasz and Kanongdate, Kamalaporn and Killi, Nur{\c c}in and Kim, Jeong-Eun and K{\i}rankaya, {\c S}erife G{\"u}ls{\"u}n and K{\v n}azovick{\'a}, Dominika and Kopeck{\'y}, Old{\v r}ich and Kostov, Vasil and Koutsikos, Nicholas and Kozic, Sebastian and Kuljanishvili, Tatia and Kumar, Biju and Kumar, Lohith and Kurita, Yoshihisa and Kurtul, Irmak and Lazzaro, Lorenzo and Lee, Laura and Lehtiniemi, Maiju and Leonardi, Giovanni and Leuven, Rob S E W and Li, Shan and Lipinskaya, Tatsiana and Liu, Fei and Lloyd, Lance and Lorenzoni, Massimo and Luna, Sergio Alberto and Lyons, Timothy J and Magellan, Kit and Malmstr{\o}m, Martin and Marchini, Agnese and Marr, Sean M and Masson, G{\'e}rard and Masson, Laurence and McKenzie, Cynthia H and Memedemin, Daniyar and Mendoza, Roberto and Minchin, Dan and Miossec, Laurence and Moghaddas, Seyed Daryoush and Moshobane, Moleseng C and Mumladze, Levan and Naddafi, Rahmat and Najafi-Majd, Elnaz and N{\u a}stase, Aurel and N{\u a}vodaru, Ion and Neal, J Wesley and Nienhuis, Sarah and Nimtim, Matura and Nolan, Emma T and Occhipinti-Ambrogi, Anna and Ojaveer, Henn and Olenin, Sergej and Olsson, Karin and Onikura, Norio and O{\textquoteright}Shaughnessy, Kathryn and Paganelli, Daniele and Parretti, Paola and Patoka, Ji{\v r}{\'\i} and Pavia, Richard Thomas B and Pellitteri-Rosa, Daniele and Pelletier-Rousseau, Mich{\`e}le and Peralta, Elfritzson M and Perdikaris, Costas and Pietraszewski, Dariusz and Piria, Marina and Pitois, Sophie and Pompei, Laura and Poulet, Nicolas and Preda, Cristina and Puntila-Dodd, Riikka and Qashqaei, Ali T and Rado{\v c}aj, Tena and Rahmani, Hossein and Raj, Smrithy and Reeves, David and Ristovska, Milica and Rizevsky, Viktor and Robertson, D Ross and Robertson, Peter and Ruykys, Laura and Saba, Abdulwakil O and Santos, Jos{\'e} M and Sar{\i}, Hasan M and Segurado, Pedro and Semenchenko, Vitaliy and Senanan, Wansuk and Simard, Nathalie and Simonovi{\'c}, Predrag and Sk{\'o}ra, Micha{\l} E and Slov{\'a}k {\v S}vol{\'\i}kov{\'a}, Krist{\'\i}na and Smeti, Evangelia and {\v S}m{\'\i}dov{\'a}, Tereza and {\v S}peli{\'c}, Ivan and Srebaliene, Greta and Stasolla, Gianluca and Stebbing, Paul and {\v S}tevove, Barbora and Suresh, Vettath R and Szajbert, Bettina and Ta, Kieu Anh T and Tarkan, Ali Serhan and Tempesti, Jonathan and Therriault, Thomas W and Tidbury, Hannah J and Top-Karaku{\c s}, Nildeniz and Tricarico, Elena and Troca, D{\'e}bora F A and Tsiamis, Konstantinos and Tuckett, Quenton M and Tutman, Pero and Uyan, Umut and Uzunova, Eliza and Vardakas, Leonidas and Velle, Gaute and Verreycken, Hugo and Vintsek, Lizaveta and Wei, Hui and Weiperth, Andr{\'a}s and Weyl, Olaf L F and Winter, Emily R and W{\l}odarczyk, Rados{\l}aw and Wood, Louisa E and Yang, Ruibin and Yap{\i}c{\i}, Sercan and Yeo, Shayne S B and Yo{\u g}urt{\c c}uo{\u g}lu, Baran and Yunnie, Anna L E and Zhu, Yunjie and Zi{\k e}ba, Grzegorz and {\v Z}it{\v n}anov{\'a}, Krist{\'\i}na and Clarke, Stacey} } @article {94388, title = {Glycation of Albumin and its Implication in Diabetes: A Comprehensive Analysis using Mass Spectrometry.}, journal = {Clin Chim Acta}, year = {2021}, month = {2021 Jun 02}, abstract = {

AIM: To understand the mechanism of glycation of albumin and effects on cysteinylation and methionine oxidation.

METHODS: The in vitro glycation of HSA and BSA was studied with varying concentrations of glucose. Clinical blood samples of diabetic subjects with varying HbA1c values, were analyzed to assess in vivo glycation. All samples and their tryptic digests were analyzed using liquid chromatography/mass spectrometry. Glycation sites were mapped on to the three-dimensional structure of the HSA and BSA.

RESULTS: A total thirty-one sites for glycation and eight sites of N-carboxymethyl-lysine (CML) modification were identified on albumin. The site selectivity of glycation was correlated with the environment of the reactive residue in the three-dimensional structure.

CONCLUSIONS: The maximum percentage glycation under extreme conditions was in the range of \~{}55 to 88\% in four weeks. Two major glycation sites K-233 and K-525 were identified, which together accounted for 40-50\% of total glycation. A correlation was observed between glycation and oxidation of methionine residues in samples glycated in vitro. The role of spatially proximate residues in facilitating the glycation process is evident. The tri- and tetra-glycated isoforms of albumin can serve as biomarkers for the severe uncontrolled diabetic state.

}, issn = {1873-3492}, doi = {10.1016/j.cca.2021.06.001}, author = {Kumari, Namita and Bandyopadhyay, Debarati and Kumar, Vinay and Venkatesh, D B and Prasad, Sujay and Prakash, Sunita and Krishnaswamy, P R and Balaram, P and Bhat, Navakanta} } @article {99331, title = {GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis}, journal = {EMBO JOURNAL}, year = {2021}, month = {09/2021}, pages = {e107766}, abstract = {

The Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear. Here, we show that the Golgi matrix protein GRASP55 directs the compartmentalized localization of key enzymes involved in glycosphingolipid (GSL) biosynthesis. GRASP55 binds to these enzymes and prevents their entry into COPI-based retrograde transport vesicles, thus concentrating them in the trans-Golgi. In genome-edited cells lacking GRASP55, or in cells expressing mutant enzymes without GRASP55 binding sites, these enzymes relocate to the cis-Golgi, which affects glycosphingolipid biosynthesis by changing flux across metabolic branch points. These findings reveal a mechanism by which a matrix protein regulates polarized localization of glycosylation enzymes in the Golgi and controls competition in glycan biosynthesis.

}, doi = {10.15252/embj.2021107766}, author = {Pothukuchi, Prathyush and Agliarulo, Ilenia and Pirozzi, Marinella and Rizzo, Riccardo and Russo, Domenico and Turacchio, Gabriele and Nuechel, Julian and Yang, Jia-Shu and Gehin, Charlotte and Capolupo, Laura and Hernandez-Corbacho, Maria Jose and Biswas, Ansuman and Vanacore, Giovanna and Dathan, Nina and Nitta, Takahiro and Henklein, Petra and Thattai, Mukund and Inokuchi, Jin-Ichi and Hsu, Victor W. and Plomann, Markus and Obeid, Lina M and Hannun, Yusuf A. and Luini, Alberto and D{\textquoteright}Angelo, Giovanni and Parashuraman, Seetharaman} } @article {102995, title = {Grasslands half-full: investigating drivers of spatial heterogeneity in ungulate occurrence in Indian Terai}, journal = {JOURNAL OF ZOOLOGY }, year = {2021}, month = {11/2021}, abstract = {

Grassland ecosystems have declined in their extent globally, driving declines in wild ungulate populations. Even within the remnant grasslands, ungulate distribution is highly heterogeneous for reasons that are not well understood. This in turn undermines both local and landscape level conservation efforts for these often-neglected ecosystems and the herbivores they support. We investigated grassland-ungulate relationships in the Terai region of North India, where wild ungulates are patchily distributed across alluvial grasslands, a besieged ecosystem. Specifically, we posited that spatial variation in grassland habitat use by swamp deer (Rucervus duvaucelii duvaucelii), hog deer (Axis porcinus) and spotted deer (Axis axis) would be explained by community composition, palatability of key grasses, and fire and flooding regimes in grasslands. Hierarchical clustering and multivariate ordination revealed that three dominant tall-grass communities and the narrowly distributed and more palatable short grass Cynodon-Oryza community were only marginally influenced by fire and flood histories. Ungulate habitat use, assessed using occupancy models for spatially correlated data, indicated that hog deer were ubiquitously distributed across the grasslands in the park (habitat use probability, Psi = 0.92, SE = 0.05) utilizing a diverse range of grassland types, while spotted deer (Psi = 0.80, SE = 0.17) and swamp deer (Psi = 0.45, SE = 0.10) occurrence within grasslands was relatively lower. Grass height and grassland extent positively influenced habitat use of swamp deer and spotted deer, respectively. However, grassland community composition, fire history, flood history and palatability were relatively uninformative predictors of fine-scale habitat use. Our study provides a robust baseline for future monitoring of grasslands and ungulates as well as insights for the design and implementation of grassland management interventions.

}, doi = {10.1111/jzo.12939}, author = {Rastogi, S. and Chanchani, P. and Sankaran, M. and Warrier, R.} } @article {97222, title = {Habitat preference and functional traits influence responses of tropical butterflies to varied habitat disturbance}, journal = {INTERNATIONAL JOURNAL OF TROPICAL INSECT SCIENCE}, year = {2021}, month = {08/2021}, abstract = {

Biodiversity is declining worldwide due to anthropogenic disturbances. There is a vital need to be able to predict the impacts of these disturbances on ecological communities. Species{\textquoteright} attributes such as habitat preference and functional morphological traits may help in uncovering broad patterns in their responses to anthropogenic habitat disturbance. We examined trait-habitat associations in 251 tropical butterfly species by measuring three morphological traits (body mass, wing length and proboscis length) and classifying species according to their habitat preference (forest, ecotone, open). We then correlated these measures (morphological traits and habitat preference) to responses of butterflies to two common habitat disturbances, i.e., a road passing through forest, and dominance of an invasive plant Lantana camara. Both evolutionary relatedness (i.e., family affiliation) and habitat preference explained considerable variation in butterfly morphological traits, suggesting a relationship between evolutionary relatedness, habitat preference and morphology. Both habitat preference and morphological traits influenced response to habitat disturbance: (a) forest roads were frequented by smaller butterflies (b) Lantana-dominated patches were depauperate in larger butterfly species and species with long probosces that are usually associated with deep-flowered forest plants, and (c) habitat preference was related to disturbance from both road and Lantana, with forest-specialized butterfly species showing a negative response. These results suggest that tropical butterflies show generalized responses to habitat disturbance according to their habitat preference and functional morphological traits.

}, doi = {10.1007/s42690-021-00609-1}, author = {Attiwilli, Suman and Karmakar, Tarun and Isvaran, Kavita and Kunte, Krushnamegh} } @article {101545, title = {A hard day{\textquoteright}s night: Patterns in the diurnal and nocturnal foraging behavior of Apis dorsata across lunar cycles and seasons.}, journal = {PLoS One}, volume = {16}, year = {2021}, month = {2021}, pages = {e0258604}, abstract = {

The giant honey bee Apis dorsata is unusual in being able to forage during both the day and the night. To date, the extent of this unique nocturnal foraging behavior and the environmental factors correlating with it have not been deeply investigated. We conducted the first systematic investigation into the nocturnal behavior of A. dorsata in Southern India by tracking the daily and nightly foraging activity of A. dorsata colonies in an urban environment for 8 months, over multiple seasons and lunar cycles. We found strong evidence that A. dorsata can behave in a manner that is "cathemeral" (active over the entire diel cycle) when environmental illumination is sufficient for nocturnal flight. However, workers were not always active even when the environment should have been bright enough for them to forage, suggesting that their nocturnal foraging behavior was also affected by seasonal changes in resource availability. The foraging activity observed during the day versus twilight versus night differed between seasons; notably, nocturnal activity rates were higher than diurnal activity rates during the winter. We found that at our study site A. dorsata routinely exhibits both diurnal and crepuscular activity, foraging just as intensely during the short twilight hours as during the day. The high foraging activity observed during the twilight and nighttime hours shows that A. dorsata colonies can extend their foraging beyond the daylight hours and reveals that foraging during these dimly lit hours is an integral part of their foraging ecology. This evidence of the importance of nocturnal and crepuscular foraging by A. dorsata paves the way for future studies examining the role of this species in nocturnal pollination networks, the contribution of nocturnal foraging to colony-level nutrition and energy budget, and the evolution of this unusual behavior. Future work comparing nocturnal activity in light polluted urban environments versus unpolluted natural environments is particularly encouraged to determine the generalizability of these findings.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0258604}, author = {Young, Allison M and Kodabalagi, Sangamesh and Brockmann, Axel and Dyer, Fred C} } @article {99936, title = {High behavioral variability mediated by altered neuronal excitability in mutant zebrafish.}, journal = {eNeuro}, year = {2021}, month = {2021 Sep 17}, abstract = {

Autism spectrum disorders (ASDs) are characterized by abnormal behavioral traits arising from neural circuit dysfunction. While a number of genes have been implicated in ASDs, in most cases, a clear understanding of how mutations in these genes lead to circuit dysfunction and behavioral abnormality is absent. The () gene is one such gene, associated with ASDs, intellectual disability and a range of other neurodevelopmental conditions. Yet, the role of AUTS2 in neural development and circuit function is not at all known. Here, we undertook functional analysis of Auts2a, the main homolog of AUTS2 in zebrafish, in the context of the escape behavior. Escape behavior in wild type zebrafish is critical for survival and is therefore, reliable, rapid, and has well-defined kinematic properties. mutant zebrafish are viable, have normal gross morphology and can generate escape behavior with normal kinematics. However, the behavior is unreliable and delayed, with high trial-to-trial variability in the latency. Using calcium imaging we probed the activity of Mauthner neurons during otic vesicle stimulation and observed lower probability of activation and reduced calcium transients in the mutants. With direct activation of Mauthner by antidromic stimulation, the threshold for activation in mutants was higher than that in wild type, even when inhibition was blocked. Taken together, these results point to reduced excitability of Mauthner neurons in auts2a mutant larvae leading to unreliable escape responses. Our results show a novel role for Auts2a in regulating neural excitability and reliability of behavior.AUTS2 is one among recently identified autism susceptibility candidate genes, whose function in neuronal circuits is unclear. Using zebrafish as a model organism, we probe the function of Auts2a (homolog of mammalian AUTS2) at the cellular, network and behavioral levels. The escape behavior of Auts2a mutant zebrafish is highly variable with normal short latency escapes, long latency escapes and total failures across trials in the same fish. This occurs because neuronal excitability is inappropriately set in the Mauthner neurons of mutants leading to large trial-to-trial variability in responses. The behavioral variability is fully explained by variability in firing action potentials in the Mauthner neuron, providing an integrative understanding of how behavioral variability arises from mutations at the genetic level.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0493-20.2021}, author = {Jha, Urvashi and Kondrychyn, Igor and Korzh, Vladimir and Thirumalai, Vatsala} } @article {99113, title = {High frequency of an otherwise rare phenotype in a small and isolated tiger population.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Sep 28}, abstract = {

Most endangered species exist today in small populations, many of which are isolated. Evolution in such populations is largely governed by genetic drift. Empirical evidence for drift affecting striking phenotypes based on substantial genetic data are rare. Approximately 37\% of tigers () in the Similipal Tiger Reserve (in eastern India) are pseudomelanistic, characterized by wide, merged stripes. Camera trap data across the tiger range revealed the presence of pseudomelanistic tigers only in Similipal. We investigated the genetic basis for pseudomelanism and examined the role of drift in driving this phenotype{\textquoteright}s frequency. Whole-genome data and pedigree-based association analyses from captive tigers revealed that pseudomelanism cosegregates with a conserved and functionally important coding alteration in (), a gene responsible for similar traits in other felid species. Noninvasive sampling of tigers revealed a high frequency of the Taqpep p.H454Y mutation in Similipal (12 individuals, allele frequency = 0.58) and absence from all other tiger populations (395 individuals). Population genetic analyses confirmed few (minimal number) tigers in Similipal, and its genetic isolation, with poor geneflow. Pairwise F (0.33) at the mutation site was high but not an outlier. Similipal tigers had low diversity at 81 single nucleotide polymorphisms (mean heterozygosity = 0.28, SD = 0.27). Simulations were consistent with founding events and drift as possible drivers for the observed stark difference of allele frequency. Our results highlight the role of stochastic processes in the evolution of rare phenotypes. We highlight an unusual evolutionary trajectory in a small and isolated population of an endangered species.

}, issn = {1091-6490}, doi = {10.1073/pnas.2025273118}, author = {Sagar, Vinay and Kaelin, Christopher B and Natesh, Meghana and Reddy, P Anuradha and Mohapatra, Rajesh K and Chhattani, Himanshu and Thatte, Prachi and Vaidyanathan, Srinivas and Biswas, Suvankar and Bhatt, Supriya and Paul, Shashi and Jhala, Yadavendradev V and Verma, Mayank M and Pandav, Bivash and Mondol, Samrat and Barsh, Gregory S and Swain, Debabrata and Ramakrishnan, Uma} } @article {90599, title = {High prevalence and diversity of Bartonella in small mammals from the biodiverse Western Ghats.}, journal = {PLoS Negl Trop Dis}, volume = {15}, year = {2021}, month = {2021 Mar}, pages = {e0009178}, abstract = {

Bartonella species are recognized globally as emerging zoonotic pathogens. Small mammals such as rodents and shrews are implicated as major natural reservoirs for these microbial agents. Nevertheless, in several tropical countries, like India, the diversity of Bartonella in small mammals remain unexplored and limited information exists on the natural transmission cycles (reservoirs and vectors) of these bacteria. Using a multi-locus sequencing approach, we investigated the prevalence, haplotype diversity, and phylogenetic affinities of Bartonella in small mammals and their associated mites in a mixed-use landscape in the biodiverse Western Ghats in southern India. We sampled 141 individual small mammals belonging to eight species. Bartonella was detected in five of the eight species, including three previously unknown hosts. We observed high interspecies variability of Bartonella prevalence in the host community. However, the overall prevalence (52.5\%) and haplotype diversity (0.9) was high for the individuals tested. Of the seven lineages of Bartonella identified in our samples, five lineages were phylogenetically related to putative zoonotic species-B. tribocorum, B. queenslandensis, and B. elizabethae. Haplotypes identified from mites were identical to those identified from their host species. This indicates that these Bartonella species may be zoonotic, but further work is necessary to confirm whether these are pathogenic and pose a threat to humans. Taken together, these results emphasize the presence of hitherto unexplored diversity of Bartonella in wild and synanthropic small mammals in mixed-use landscapes. The study also highlights the necessity to assess the risk of spillover to humans and other incidental hosts.

}, issn = {1935-2735}, doi = {10.1371/journal.pntd.0009178}, author = {Ansil, B R and Mendenhall, Ian H and Ramakrishnan, Uma} } @article {103918, title = {HillTau: A fast, compact abstraction for model reduction in biochemical signaling networks.}, journal = {PLoS Comput Biol}, volume = {17}, year = {2021}, month = {2021 11}, pages = {e1009621}, abstract = {

Signaling networks mediate many aspects of cellular function. The conventional, mechanistically motivated approach to modeling such networks is through mass-action chemistry, which maps directly to biological entities and facilitates experimental tests and predictions. However such models are complex, need many parameters, and are computationally costly. Here we introduce the HillTau form for signaling models. HillTau retains the direct mapping to biological observables, but it uses far fewer parameters, and is 100 to over 1000 times faster than ODE-based methods. In the HillTau formalism, the steady-state concentration of signaling molecules is approximated by the Hill equation, and the dynamics by a time-course tau. We demonstrate its use in implementing several biochemical motifs, including association, inhibition, feedforward and feedback inhibition, bistability, oscillations, and a synaptic switch obeying the BCM rule. The major use-cases for HillTau are system abstraction, model reduction, scaffolds for data-driven optimization, and fast approximations to complex cellular signaling.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1009621}, author = {Bhalla, Upinder S} } @article {86449, title = {Histone chaperone APLF level dictate implantation of mouse embryo}, journal = {J Cell Sci}, volume = {134}, year = {2021}, month = {12/2020}, abstract = {

Our recent findings demonstrated that histone chaperone and DNA repair factor Aprataxin PNK like factor (APLF) could regulate Epithelial to mesenchymal transition (EMT) during reprogramming of murine fibroblast and in breast cancer metastasis. So, we investigated the function of APLF in EMT associated with mouse development. Here we show that APLF is predominantly enhanced in trophectoderm and lineages derived from trophectoderm in pre and post-implantation embryos. Downregulation of APLF induced hatching of embryos in vitro with a significant increase in Cdh1 and Cdx2 expression. Aplf shRNA microinjected embryos failed to implant in vivo Rescue experiments neutralized the knockdown effects of APLF both in vitro and in vivo Reduced expression of Snai2, Tead4 and the gain in Cdh1 and sFlt1 level marked the differentiation of APLF-knocked down Trophoblast Stem Cells that might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role of APLF during implantation and post-implantation development of mouse embryos. We anticipate that APLF might contribute to the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.

}, doi = {10.1242/jcs.246900}, author = {Varghese, PC and Rajam, SM and Nandy, D and Jory, A and Mukherjee, A and Dutta, D} } @article {88404, title = {The Impact of Mistranslation on Phenotypic Variability and Fitness.}, journal = {Evolution}, year = {2021}, month = {01/2021}, abstract = {

Phenotypic variation is widespread in natural populations, and can significantly alter population ecology and evolution. Phenotypic variation often reflects underlying genetic variation, but also manifests via non-heritable mechanisms. For instance, translation errors result in about 10\% of cellular proteins carrying altered sequences. Thus, proteome diversification arising from translation errors can potentially generate phenotypic variability, in turn increasing variability in the fate of cells or of populations. However, the link between protein diversity and phenotypic variability remains unverified. We manipulated mistranslation levels in Escherichia coli, and measured phenotypic variability between single cells (individual level variation), as well as replicate populations (population level variation). Monitoring growth and survival, we find that mistranslation indeed increases variation across E. coli cells, but does not consistently increase variability in growth parameters across replicate populations. Interestingly, although any deviation from the wild type (WT) level of mistranslation reduces fitness in an optimal environment, the increased variation is associated with a survival benefit under stress. Hence, we suggest that mistranslation-induced phenotypic variation can impact growth and survival and has the potential to alter evolutionary trajectories. This article is protected by copyright. All rights reserved.

}, doi = {10.1111/evo.14179}, author = {Samhita, Laasya and Raval, Parth K and Stephenson, G and Thutupalli, Shashi and Agashe, Deepa} } @article {102564, title = {The importance of history in understanding large tree mortality in African savannas}, journal = {ECOGRAPHY }, year = {2021}, month = {11/2021}, abstract = {

Fire and elephant herbivory are major drivers of large tree mortality in savanna ecosystems. Although the spatial variation of these agents is well studied, less attention has been paid to how disturbance history influences tree mortality over time. In a long-term cohort study, we examined how the sequence of fire- and elephant-induced damage influences mortality of trees and determined whether risk of mortality is compounded over time. Data on over 2500 large trees were collected from 22 transects in Kruger National Park, South Africa, in 2006, and trees were resampled in 2008, 2011, 2015 and 2018. Over the 12-year period, we recorded a cumulative mortality of 47.6\% with an estimated annual mortality of 3-5\% from 2006 through 2015 and an increase to 8.8\% in 2018. The main attributed agent of tree mortality was elephant damage, occurring either once or across multiple census periods. A classification tree analysis partitioned over different census periods showed that the probability of mortality of the 10 most common tree species depended not only on the type and intensity of elephant-induced damage and fire but also on the historical sequence of damage by these agents. Elephant damage to the main stem incurred up to 12 years earlier increased risk of mortality for large trees, especially in combination with fire damage. As expected, vulnerability to damage and risk of mortality varied among species, resulting in the potential for long-term changes in species composition over large areas. Overall, this study highlights how multiple interacting agents cause emergent and lagging patterns of mortality risk for large trees in savanna ecosystems, a result that only becomes apparent through fine resolution and long-term tracking of cohorts.

}, doi = {10.1111/ecog.06012}, author = {Das, Arundhati and Thaker, Maria and Coetsee, Corli and Slotow, Rob and Vanak, Abi T.} } @article {101901, title = {In Vitro Anticancer Activity of Root{\textquoteright}s Extract toward Human Cervical Cancer and Identification of Potential Bioactive Compounds.}, journal = {Biomed Res Int}, volume = {2021}, year = {2021}, month = {2021}, pages = {4259777}, abstract = {

is traditionally used to cure several diseases including cancer, wounds, and hypertension. The present study was designed to investigate the anticancer activity of the methanolic root extract of (IC-MeOH). The water-soluble tetrazolium-1 and colony formation assays were used to check the proliferation ability of the cells. Cell apoptosis and cell cycle were measured by flow cytometry-based fluorescence-activated cell sorting. The ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was used for the metabolites profiling of IC-MeOH. Based on high-mass accuracy, spectral data, and previous reports, tentative compound identifications were assigned. Our findings revealed that IC-MeOH inhibited the proliferation of HeLa and CaSki cells. The plant extract was also found to induce a concentration- and time-dependent apoptosis and cell cycle arrest in the G0/G1 phase (IC value) in CaSki cell line. Analysis of IC-MeOH permitted the identification of 10 compounds already reported for their anticancer activity, epicatechin, curcumin, (-)-yatein, caffeic acid, myricetin, jatrorrhizine, harmaline, cinnamaldehyde, dobutamine, and syringin. In conclusion, IC-MeOH is a rich source of cytotoxic metabolites that inhibits human cervical cancer proliferation apoptosis and cell cycle arrest.

}, issn = {2314-6141}, doi = {10.1155/2021/4259777}, author = {Nayim, Paul and Sudhir, Krishna and Mbaveng, Armelle T and Kuete, Victor and Sanjukta, Mukherjee} } @article {91672, title = {Influence of Disease-Causing Mutations on Protein Structural Networks.}, journal = {Front Mol Biosci}, volume = {7}, year = {2021}, month = {2020}, pages = {620554}, abstract = {

The interactions between residues in a protein tertiary structure can be studied effectively using the approach of protein structure network (PSN). A PSN is a node-edge representation of the structure with nodes representing residues and interactions between residues represented by edges. In this study, we have employed weighted PSNs to understand the influence of disease-causing mutations on proteins of known 3D structures. We have used manually curated information on disease mutations from UniProtKB/Swiss-Prot and their corresponding protein structures of wildtype and disease variant from the protein data bank. The PSNs of the wildtype and disease-causing mutant are compared to analyse variation of global and local dissimilarity in the overall network and at specific sites. We study how a mutation at a given site can affect the structural network at a distant site which may be involved in the function of the protein. We have discussed specific examples of the disease cases where the protein structure undergoes limited structural divergence in their backbone but have large dissimilarity in their all atom networks and vice versa, wherein large conformational alterations are observed while retaining overall network. We analyse the effect of variation of network parameters that characterize alteration of function or stability.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2020.620554}, author = {Prabantu, Vasam Manjveekar and Naveenkumar, Nagarajan and Srinivasan, Narayanaswamy} } @article {83639, title = {Inhibition of plant pathogenic fungi by endophytic Trichoderma spp. through mycoparasitism and volatile organic compounds.}, journal = {Microbiol Res}, volume = {242}, year = {2021}, month = {2020 Sep 17}, pages = {126595}, abstract = {

Antagonism of plant pathogenic fungi by endophytic fungi is a well-known phenomenon. In plate assays, the antagonism could be due to mycoparasitism, competition for space or antibiosis, involving a chemical diffusate, or a volatile organic compound (VOC). In this study, we demonstrate that besides mycoparasitism, VOCs play a major role in antagonism of pathogenic fungi by four endophytic fungi belonging to the genus Trichoderma. Using a double-plate assay, we show that all the four endophytic Trichoderma species significantly inhibited mycelial growth of three of the four pathogens, (Sclerotinia sclerotiorum-TSS, Sclerotium rolfsii-CSR and Fusarium oxysporum-CFO), while that of Macrophomina phaseolina-CMP was not affected. GC-MS analysis of the pure cultures of one of the endophytic fungi studied, namely, Trichoderma longibrachiatum strain 2 (Acc. No. MK751758) and the pathogens, F. oxysporum-CFO and M. phaseolina-CMP revealed the presence of several VOCs including hydrocarbons, alcohols, ketones, aldehydes, esters, acids, ethers and different classes of terpenes. In mixed double plates, where the endophyte was grown along with either of the two plant pathogens, F. oxysporum-CFO or M. phaseolina-CMP, there was an induction of a number of new VOCs that were not detected in the pure cultures of either the endophyte or the pathogens. Several of these new VOCs are reported to possess antifungal and cytotoxic activity. We discuss these results and highlight the importance of such interactions in endophyte-pathogen interactions.

}, issn = {1618-0623}, doi = {10.1016/j.micres.2020.126595}, author = {Rajani, P and Rajasekaran, C and Vasanthakumari, M M and Olsson, Shannon B and Ravikanth, G and Uma Shaanker, R} } @article {88160, title = {InsectOR-Webserver for sensitive identification of insect olfactory receptor genes from non-model genomes.}, journal = {PLoS One}, volume = {16}, year = {2021}, month = {2021}, pages = {e0245324}, abstract = {

Insect Olfactory Receptors (ORs) are diverse family of membrane protein receptors responsible for most of the insect olfactory perception and communication, and hence they are of utmost importance for developing repellents or pesticides. Accurate gene prediction of insect ORs from newly sequenced genomes is an important but challenging task. We have developed a dedicated webserver, {\textquoteright}insectOR{\textquoteright}, to predict and validate insect OR genes using multiple gene prediction algorithms, accompanied by relevant validations. It is possible to employ this server nearly automatically and perform rapid prediction of the OR gene loci from thousands of OR-protein-to-genome alignments, resolve gene boundaries for tandem OR genes and refine them further to provide more complete OR gene models. InsectOR outperformed the popular genome annotation pipelines (MAKER and NCBI eukaryotic genome annotation) in terms of overall sensitivity at base, exon and locus level, when tested on two distantly related insect genomes. It displayed more than 95\% nucleotide level precision in both tests. Finally, given the same input data and parameters, InsectOR missed less than 2\% gene loci, in contrast to 55\% loci missed by MAKER for Drosophila melanogaster. The webserver is freely available on the web at http://caps.ncbs.res.in/insectOR/ and the basic package can be downloaded from https://github.com/sdk15/insectOR for local use. This tool will allow biologists to perform quick preliminary identification of insect olfactory receptor genes from newly sequenced genomes and also assist in their further detailed annotation. Its usage can also be extended to other divergent gene families.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0245324}, author = {Karpe, Snehal Dilip and Tiwari, Vikas and Ramanathan, Sowdhamini} } @article {103403, title = {Intact in situ Preparation of the Drosophila melanogaster Lymph Gland for a Comprehensive Analysis of Larval Hematopoiesis }, journal = {Bio Protoc}, volume = {11}, year = {2021}, month = {11/2021}, pages = {e4204}, abstract = {

Blood cells have a limited lifespan and are replenished by a small number of hematopoietic stem and progenitor cells (HSPCs). Adult vertebrate hematopoiesis occurs in the bone marrow, liver, and spleen, rendering a comprehensive analysis of the entire HSPC pool nearly impossible. The Drosophila blood system is well studied and has developmental, molecular, and functional parallels with that of vertebrates. Unlike vertebrates, post-embryonic hematopoiesis in Drosophila is essentially restricted to the larval lymph gland (LG), a multi-lobed organ that flanks the dorsal vessel. Because the anterior-most or primary lobes of the LG are easy to dissect out, their cellular and molecular characteristics have been studied in considerable detail. The 2-3 pairs of posterior lobes are more delicate and fragile and have largely been ignored. However, posterior lobes harbor a significant blood progenitor pool, and several hematopoietic mutants show differences in phenotype between the anterior and posterior lobes. Hence, a comprehensive analysis of the LG is important for a thorough understanding of Drosophila hematopoiesis. Most studies focus on isolating the primary lobes by methods that generally dislodge and damage other lobes. To obtain preparations of the whole LG, including intact posterior lobes, here we provide a detailed protocol for larval fillet dissection. This allows accessing and analyzing complete LG lobes, along with dorsal vessel and pericardial cells. We demonstrate that tissue architecture and integrity is maintained and provide methods for quantitative analysis. This protocol can be used to quickly and effectively isolate complete LGs from first instar larval to pupal stages and can be implemented with ease.

}, doi = {10.21769/BioProtoc.4204 }, author = {Rodrigues, Diana and Vijayraghavan, K. and Waltzer, Lucas and Inamdar, Maneesha S} } @article {92882, title = {Interactions between all pairs of neighboring trees in 16 forests worldwide reveal details of unique ecological processes in each forest, and provide windows into their evolutionary histories.}, journal = {PLoS Comput Biol}, volume = {17}, year = {2021}, month = {2021 Apr}, pages = {e1008853}, abstract = {

When Darwin visited the Galapagos archipelago, he observed that, in spite of the islands{\textquoteright} physical similarity, members of species that had dispersed to them recently were beginning to diverge from each other. He postulated that these divergences must have resulted primarily from interactions with sets of other species that had also diverged across these otherwise similar islands. By extrapolation, if Darwin is correct, such complex interactions must be driving species divergences across all ecosystems. However, many current general ecological theories that predict observed distributions of species in ecosystems do not take the details of between-species interactions into account. Here we quantify, in sixteen forest diversity plots (FDPs) worldwide, highly significant negative density-dependent (NDD) components of both conspecific and heterospecific between-tree interactions that affect the trees{\textquoteright} distributions, growth, recruitment, and mortality. These interactions decline smoothly in significance with increasing physical distance between trees. They also tend to decline in significance with increasing phylogenetic distance between the trees, but each FDP exhibits its own unique pattern of exceptions to this overall decline. Unique patterns of between-species interactions in ecosystems, of the general type that Darwin postulated, are likely to have contributed to the exceptions. We test the power of our null-model method by using a deliberately modified data set, and show that the method easily identifies the modifications. We examine how some of the exceptions, at the Wind River (USA) FDP, reveal new details of a known allelopathic effect of one of the Wind River gymnosperm species. Finally, we explore how similar analyses can be used to investigate details of many types of interactions in these complex ecosystems, and can provide clues to the evolution of these interactions.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1008853}, author = {Wills, Christopher and Wang, Bin and Fang, Shuai and Wang, Yunquan and Jin, Yi and Lutz, James and Thompson, Jill and Harms, Kyle E and Pulla, Sandeep and Pasion, Bonifacio and Germain, Sara and Liu, Heming and Smokey, Joseph and Su, Sheng-Hsin and Butt, Nathalie and Chu, Chengjin and Chuyong, George and Chang-Yang, Chia-Hao and Dattaraja, H S and Davies, Stuart and Ediriweera, Sisira and Esufali, Shameema and Fletcher, Christine Dawn and Gunatilleke, Nimal and Gunatilleke, Savi and Hsieh, Chang-Fu and He, Fangliang and Hubbell, Stephen and Hao, Zhanqing and Itoh, Akira and Kenfack, David and Li, Buhang and Li, Xiankun and Ma, Keping and Morecroft, Michael and Mi, Xiangcheng and Malhi, Yadvinder and Ong, Perry and Rodriguez, Lillian Jennifer and Suresh, H S and Sun, I Fang and Sukumar, Raman and Tan, Sylvester and Thomas, Duncan and Uriarte, Maria and Wang, Xihua and Wang, Xugao and Yao, T L and Zimmermann, Jess} } @article {91470, title = {An interdependent network of functional enhancers regulates transcription and EZH2 loading at the INK4a/ARF locus.}, journal = {Cell Rep}, volume = {34}, year = {2021}, month = {2021 Mar 23}, pages = {108898}, abstract = {

The INK4a/ARF locus encodes important cell-cycle regulators p14, p15, and p16. The neighboring gene desert to this locus is the most reproducible GWAS hotspot that harbors one of the densest enhancer clusters in the genome. However, how multiple enhancers that overlap with GWAS variants regulate the INK4a/ARF locus is unknown, which is an important step in linking genetic variation with associated diseases. Here, we show that INK4a/ARF promoters interact with a subset of enhancers in the cluster, independent of their H3K27ac and eRNA levels. Interacting enhancers transcriptionally control each other and INK4a/ARF promoters over long distances as an interdependent single unit. The deletion of even a single interacting enhancer results in an unexpected collapse of the entire enhancer cluster and leads to EZH2 enrichment on promoters in an ANRIL-independent manner. Dysregulated genes genome-wide mimic 9p21-associated diseases under these scenarios. Our results highlight intricate dependencies of promoter-interacting enhancers on each other.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2021.108898}, author = {Farooq, Umer and Saravanan, Bharath and Islam, Zubairul and Walavalkar, Kaivalya and Singh, Anurag Kumar and Jayani, Ranveer Singh and Meel, Sweety and Swaminathan, Sudha and Notani, Dimple} } @article {89662, title = {Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites.}, journal = {Biol Open}, year = {2021}, month = {2021 Feb 17}, abstract = {

During phospholipase C-β (PLC-β) signalling in photoreceptors, the phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS). Depletion of RDGB or its mis-localization away from the ER-PM MCS results in multiple defects in photoreceptor function. Previously, the interaction between the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be essential for accurate localization to ER-PM MCS. Here, we report that the FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this also requires the function of the C-terminal domains, DDHD and LNS2. Mutations in each of these domains results in mis-localization of RDGB leading to loss of function. While the LNS2 domain is necessary, it is not sufficient for the correct localization of RDGB, which also requires the C-terminal DDHD domain. The function of the DDHD domain is mediated through an intramolecular interaction with the LNS2 domain. Thus, interactions between the additional domains in a multi-domain PITP together lead to accurate localization at the MCS and signalling function.

}, issn = {2046-6390}, doi = {10.1242/bio.057422}, author = {Basak, Bishal and Krishnan, Harini and Padinjat, Raghu} } @article {100559, title = {Invasive nitrogen-fixing plants increase nitrogen availability and cycling rates in a montane tropical grassland}, journal = {PLANT ECOLOGY }, year = {2021}, month = {09/2021}, abstract = {

Invasive plants can impact nutrient cycling, potentially creating positive feedbacks for further invasion. We studied the impact of three woody nitrogen (N)-fixing invasive plant species on soil N-cycling and phosphatase activity in a montane tropical forest-grassland mosaic in the Nilgiri Biosphere Reserve in southern India, an ecosystem with \> 100-year history of biological invasions. Soils were collected over a year from patches invaded by Acacia mearnsii, Cytisus scoparius, and Ulex europaeus, and from uninvaded grasslands, to assess inorganic N-availability and N-mineralization rates (using in situ open-top mineralization tubes). Phosphatase activity was measured from soils collected at the beginning of the growing season. Soils of invaded areas had higher inorganic N-availability and phosphatase activity than soils of uninvaded areas. Whilst net N-mineralization rates were unchanged between invaded and uninvaded sites, net nitrification rates were higher and net ammonification rates lower in invaded areas, particularly in the dry season. Impacts of C. scoparius and U. europaeus on these variables were similar to each other, and lower than the impacts of A. mearnsii. These results show that invasive N-fixers are significantly altering nutrient availability and cycling, and also changing the proportion of the forms of inorganic N available, in the Nilgiri grasslands. Restoration activities in these invaded grasslands should explore soil N management strategies such as soil C amendments and planting of specific native species, in conjunction with other strategies, to control invasive plants.

}, doi = {10.1007/s11258-021-01188-4}, author = {Raghurama, Manaswi and Sankaran, Mahesh} } @article {94543, title = {IP3-mediated Ca2+ signals regulate larval to pupal transition under nutrient stress through the H3K36 methyltransferase Set2.}, journal = {Development}, volume = {148}, year = {2021}, month = {2021 Jun 01}, abstract = {

Persistent loss of dietary protein usually signals a shutdown of key metabolic pathways. In Drosophila larvae that have reached a {\textquoteright}critical weight{\textquoteright} and can pupariate to form viable adults, such a metabolic shutdown would needlessly lead to death. Inositol 1,4,5-trisphosphate-mediated calcium (IP3/Ca2+) release in some interneurons (vGlutVGN6341) allows Drosophila larvae to pupariate on a protein-deficient diet by partially circumventing this shutdown through upregulation of neuropeptide signaling and the expression of ecdysone synthesis genes. Here, we show that IP3/Ca2+ signals in vGlutVGN6341 neurons drive expression of Set2, a gene encoding Drosophila Histone 3 Lysine 36 methyltransferase. Furthermore, Set2 expression is required for larvae to pupariate in the absence of dietary protein. IP3/Ca2+ signal-driven Set2 expression upregulates key Ca2+-signaling genes through a novel positive-feedback loop. Transcriptomic studies, coupled with analysis of existing ChIP-seq datasets, identified genes from larval and pupal stages that normally exhibit robust H3K36 trimethyl marks on their gene bodies and concomitantly undergo stronger downregulation by knockdown of either the intracellular Ca2+ release channel IP3R or Set2. IP3/Ca2+ signals thus regulate gene expression through Set2-mediated H3K36 marks on select neuronal genes for the larval to pupal transition.

}, issn = {1477-9129}, doi = {10.1242/dev.199018}, author = {Mitra, Rishav and Richhariya, Shlesha and Jayakumar, Siddharth and Notani, Dimple and Hasan, Gaiti} } @article {100557, title = {Isolation and Quantification of Mouse γδT-cells and .}, journal = {Bio Protoc}, volume = {11}, year = {2021}, month = {2021 Sep 05}, pages = {e4148}, abstract = {

The skin plays an important role in protecting the body from pathogens and chemicals in the external environment. Upon injury, a healing program is rapidly initiated and involves extensive intercellular communication to restore tissue homeostasis. The deregulation of this crosstalk can lead to abnormal healing processes and is the foundation of many skin diseases. A relatively overlooked cell type that nevertheless plays critical roles in skin homeostasis, wound repair, and disease is the dendritic epidermal T cells (DETCs), which are also called γδT-cells. Given their varied roles in both physiological and pathological scenarios, interest in the regulation and function of DETCs has substantially increased. Moreover, their ability to regulate other immune cells has garnered substantial attention for their potential role as immunomodulators and in immunotherapies. In this article, we describe a protocol to isolate and culture DETCs and analyse them within the skin. These approaches will facilitate the investigation of their crosstalk with other cutaneous cells and the mechanisms by which they influence the status of the skin. Graphic abstract: Overall workflow to analyse DETCs and .

}, issn = {2331-8325}, doi = {10.21769/BioProtoc.4148}, author = {Rana, Isha and Badarinath, Krithika and Zirmire, Ravindra K and Jamora, Colin} } @article {102258, title = {Jumping in lantern bugs (Hemiptera, Fulgoridae).}, journal = {J Exp Biol}, year = {2021}, month = {2021 Nov 10}, abstract = {

Lantern bugs are amongst the largest of the jumping hemipteran bugs with body lengths reaching 44 mm and their masses 0.7 g. They are up to 600 times heavier than smaller hemipterans that jump powerfully using catapult mechanisms to store energy. Does a similar mechanism also propel jumping in these much larger insects? The jumping performance of two species of lantern bugs (Hemiptera, Auchenorrhyncha, family Fulgoridae) from India and Malaysia was therefore analysed from high-speed videos. The kinematics showed that jumps were propelled by rapid and synchronous movements of both hind legs with their trochantera moving first. The hind legs were 20-40\% longer than the front legs, which was attributable to longer tibiae. It took 5-6 ms to accelerate to take-off velocities reaching 4.65 m s-1 in the best jumps by female Kalidasa lanata. During these jumps, adults experienced an acceleration of 77 g, required an energy expenditure of 4800 {\textmu}J, a power output of 900 mW and exerted a force of 400 mN. The required power output of the thoracic jumping muscles was 21,000 W kg-1, 40 times greater than the maximum active contractile limit of muscle. Such a jumping performance therefore required a power amplification mechanism with energy storage in advance of the movement as in their smaller relatives. These large lantern bugs are near isometrically scaled up versions of their smaller relatives, still achieve comparable, if not higher, take-off velocities, and outperform other large jumping insects such as grasshoppers.

}, issn = {1477-9145}, doi = {10.1242/jeb.243361}, author = {Burrows, M and Ghosh, A and Sutton, G P and Yeshwanth, H M and Rogers, S M and Sane, S P} } @inbook {88400, title = {Label-Free Quantification of Phosphoinositides in Drosophila by Mass Spectrometry.}, booktitle = {Phosphoinositides}, volume = {2251}, number = {Methods Mol Biol}, year = {2021}, month = {2021}, pages = {19-37}, publisher = {Humana-Springer}, organization = {Humana-Springer}, abstract = {

Phosphoinositides (PIs), the seven phosphorylated derivatives of phosphatidylinositol, are recognized as key molecules in the control of multiple molecular events in eukaryotic cells. Within cells, PIs are low-abundance lipids making their detection and quantification challenging. While many methods that allow radiolabeling and quantification of PIs in the context of cultured cells are available, these are not useful in the context of in vivo animal models where cell and developmental processes are best studied. In this chapter, we describe radionuclide-free, mass spectrometry-based methods for the detection and quantification of PIs from Drosophila tissues in vivo. The use of these methods should facilitate the discovery of novel modes by which PIs regulate cellular and developmental processes in complex metazoans.

}, isbn = {978-1-0716-1141-8}, doi = {10.1007/978-1-0716-1142-5_2}, author = {Ghosh, Avishek and Raghu, Padinjat} } @article {89658, title = {Large frugivores matter more on an island: Insights from island-mainland comparison of plant-frugivore communities.}, journal = {Ecol Evol}, volume = {11}, year = {2021}, month = {2021 Feb}, pages = {1399-1412}, abstract = {

Endozoochory, a mutualistic interaction between plants and frugivores, is one of the key processes responsible for maintenance of tropical biodiversity. Islands, which have a smaller subset of plants and frugivores when compared with mainland communities, offer an interesting setting to understand the organization of plant-frugivore communities vis-a-vis the mainland sites. We examined the relative influence of functional traits and phylogenetic relationships on the plant-seed disperser interactions on an island and a mainland site. The island site allowed us to investigate the organization of the plant-seed disperser community in the natural absence of key frugivore groups (bulbuls and barbets) of Asian tropics. The endemic Narcondam Hornbill was the most abundant frugivore on the island and played a central role in the community. Species strength of frugivores (a measure of relevance of frugivores for plants) was positively associated with their abundance. Among plants, figs had the highest species strength and played a central role in the community. Island-mainland comparison revealed that the island plant-seed disperser community was more asymmetric, connected, and nested as compared to the mainland community. Neither phylogenetic relationships nor functional traits (after controlling for phylogenetic relationships) were able to explain the patterns of interactions between plants and frugivores on the island or the mainland pointing toward the diffused nature of plant-frugivore interactions. The diffused nature is a likely consequence of plasticity in foraging behavior and trait convergence that contribute to governing the interactions between plants and frugivores. This is one of the few studies to compare the plant-seed disperser communities between a tropical island and mainland and demonstrates key role played by a point-endemic frugivore in seed dispersal on island.

}, issn = {2045-7758}, doi = {10.1002/ece3.7151}, author = {Naniwadekar, Rohit and Gopal, Abhishek and Page, Navendu and Ghuman, Sartaj and Ramachandran, Vivek and Joshi, Jahnavi} } @article {99939, title = {Large herbivores suppress liana infestation in an African savanna.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Oct 12}, abstract = {

African savannas are the last stronghold of diverse large-mammal communities, and a major focus of savanna ecology is to understand how these animals affect the relative abundance of trees and grasses. However, savannas support diverse plant life-forms, and human-induced changes in large-herbivore assemblages-declining wildlife populations and their displacement by livestock-may cause unexpected shifts in plant community composition. We investigated how herbivory affects the prevalence of lianas (woody vines) and their impact on trees in an East African savanna. Although scarce (\<2\% of tree canopy area) and defended by toxic latex, the dominant liana, (Apocynaceae), was eaten by 15 wild large-herbivore species and was consumed in bulk by native browsers during experimental cafeteria trials. In contrast, domesticated ungulates rarely ate lianas. When we experimentally excluded all large herbivores for periods of 8 to 17 y (simulating extirpation), liana abundance increased dramatically, with up to 75\% of trees infested. Piecewise exclusion of different-sized herbivores revealed functional complementarity among size classes in suppressing lianas. Liana infestation reduced tree growth and reproduction, but herbivores quickly cleared lianas from trees after the removal of 18-y-old exclosure fences (simulating rewilding). A simple model of liana contagion showed that, without herbivores, the long-term equilibrium could be either endemic (liana-tree coexistence) or an all-liana alternative stable state. We conclude that ongoing declines of wild large-herbivore populations will disrupt the structure and functioning of many African savannas in ways that have received little attention and that may not be mitigated by replacing wildlife with livestock.

}, issn = {1091-6490}, doi = {10.1073/pnas.2101676118}, author = {Coverdale, Tyler C and O{\textquoteright}Connell, Ryan D and Hutchinson, Matthew C and Savagian, Amanda and Kartzinel, Tyler R and Palmer, Todd M and Goheen, Jacob R and Augustine, David J and Sankaran, Mahesh and Tarnita, Corina E and Pringle, Robert M} } @article {105151, title = {Life at the borderline: Responses of Ganges river dolphins to dry-season flow regulation of river and canal habitats by the Farakka barrage}, journal = {AQUATIC CONSERVATION-MARINE AND FRESHWATER ECOSYSTEMS }, year = {2021}, month = {12/2021}, abstract = {

Modification of river flows by dams and barrages has fragmented riverine habitats and threatened the survival of Indian subcontinental river dolphins. In this study, habitat use by endangered Ganges river dolphins in response to dry-season operations (December-March) of the Farakka barrage on the Ganga River, located about 20 km upstream of the India-Bangladesh border, was assessed. Ten surveys were conducted in: (i) the Ganga River below the barrage, where rapid changes in water levels were expected owing to barrage operations; (ii) the Farakka feeder canal with stable water levels; and (iii) the Hooghly River downstream of the canal. Dolphin distribution, water depth, fishing boat count and temperature were recorded in all surveys and the data were analysed in a dynamic occupancy modelling framework. Temporal trends in river discharge, primary productivity and fish availability were also estimated to explain river dolphin responses. Occupancy and colonization by dolphins increased in all stretches by spring/March, correlated with rising water temperature and increased fishing intensity, which was related to upstream migration of hilsa fish. In the Ganga River, dolphin occupancy in deep river pools remained stable, but resulted in increased overlap with fisheries as river flow declined. The feeder canal, with stable flows, witnessed increased colonization by dolphins, but also greater risk of bycatch in fishing nets. The canal that appeared as a hydrological refuge thus became an {\textquoteright}ecological trap{\textquoteright}. The findings highlight the need for integration of flow maintenance and fishery regulations in the monitoring and management of canals as effective refuges for riverine species. We advocate the inclusion of ecological flow criteria and fishery regulations to reduce dolphin bycatch mortality, in the context of establishing river dolphin conservation plans and transboundary water-sharing guidelines. The revision of the India-Bangladesh water-sharing treaty in 2026 could incorporate the above considerations.

}, doi = {10.1002/aqc.3763}, author = {Samad, Imran and Kelkar, Nachiket and Krishnaswamy, Jagdish} } @article {102047, title = {Ligand Docking Methods to Recognize Allosteric Inhibitors for G-Protein-Coupled Receptors.}, journal = {Bioinform Biol Insights}, volume = {15}, year = {2021}, month = {2021}, pages = {11779322211037769}, abstract = {

G-protein-coupled receptors (GPCRs) are membrane proteins which play an important role in many cellular processes and are excellent drug targets. Despite the existence of several US Food and Drug Administration (FDA)-approved GPCR-targeting drugs, there is a continuing challenge of side effects owing to the nonspecific nature of drug binding. We have investigated the diversity of the ligand binding site for this class of proteins against their cognate ligands using computational docking, even if their structures are known already in the ligand-complexed form. The cognate ligand of some of these receptors dock at allosteric binding site with better score than the binding at the conservative site. Interestingly, amino acid residues at such allosteric binding site are not conserved across GPCR subfamilies. Such a computational approach can assist in the prediction of specific allosteric binders for GPCRs.

}, issn = {1177-9322}, doi = {10.1177/11779322211037769}, author = {Harini, K and Jayashree, S and Tiwari, Vikas and Vishwanath, Sneha and Sowdhamini, Ramanathan} } @article {102994, title = {Linkers: A synergistic way for the synthesis of chimeric proteins.}, journal = {Protein Expr Purif}, volume = {191}, year = {2021}, month = {2021 Nov 10}, pages = {106012}, abstract = {

In the cell, the protein domains are attached with the short oligopeptide, commonly known as linker peptide. Besides bridging, the linker assists in the domain-domain interaction and protein folding into the peculiar conformations. Linkers allow or control the movement of protein domains in the dynamic cellular environment. The recent advances in the recombinant DNA technology enable the construction of multiple gene constructs in an open reading frame. The express sequences can work in a cascade to cater for myriad functions. This trend has given momentum to incorporating bridge sequences (linker) that essentially separates the independent domains. According to the cellular need, the bridging partner can be spaced at a secure gap or requires attaching or interacting physically. The flexible or rigid linker can help to achieve such conformations in chimeric fusion proteins. The linker can improve solubility, proteolytic resistance and stability of such fusion proteins. Recently, linker aided protein switches and antibody-drug conjugates are gaining the attention of researchers worldwide. Here, we thoroughly reviewed the types of the linker, strategies for linker engineering and the composition of a linker.

}, issn = {1096-0279}, doi = {10.1016/j.pep.2021.106012}, author = {Patel, Dharti Keyur and Menon, Dhanya V and Patel, Darshan H and Dave, Gayatri} } @article {102253, title = {Linking flow alteration with fish assemblage structure in a river regulated by a small hydropower project in the Western Ghats of Karnataka, India}, journal = {RIVER RESEARCH AND APPLICATIONS}, year = {2021}, month = {10/2021}, abstract = {

Small hydropower projects (SHPs) are promoted as low-impact alternatives for large hydropower. SHPs are generally commissioned on small- to medium-sized mountainous rivers, often in biodiverse regions, with backing in the form of subsidies, facultative policies and exemption from impact assessments as they are considered {\textquoteright}green{\textquoteright}. However, the ecological impacts of SHPs are understudied especially in highly seasonal tropical streams of Western Ghats of India, a global biodiversity hotspot and a distinct freshwater fish eco-region. We compared SHP-affected segments of a dammed and an undammed river in the Western Ghats of Karnataka, to assess how altered flow regime affects seasonal variability in habitat and water quality, and influences fish assemblage structure. We found that flow alteration by the SHP varied between different segments of the dammed river and with season. Furthermore, the nature of flow alteration influenced habitat variability, water quality and fish assemblage response in the dammed river. We observed that the dewatered segment of the dammed river experienced a lotic to lentic shift in habitat and water quality, which favoured fish species with eurytopic affinities. Fluctuating flows in the downstream segment subdued natural variability in flow regime and created novel habitats and water-quality conditions, affecting fish assemblages. The upstream segment of the dammed river retained natural variability in habitat and water quality, but did not mimic the undammed river in terms of fish composition. We also observed potential constraints on recruitment for migratory species of fish in the dammed river. Based on our results, we suggest how the placement of dewatered segment, and timing the closure of SHP operation in dry season based on ecological thresholds are potential solutions to mitigate the impacts of the SHPs. Furthermore, we recommend effective impact assessments, and adaptive management with active interventions to maintain genetic and ecological connectivity, as key to enhance the sustainability of the SHPs.

}, doi = {10.1002/rra.3882}, author = {Rao, Shishir and Krishnaswamy, Jagdish and Bhalla, Ravinder Singh} } @article {105152, title = {Long-term high densities of African elephants clear the understorey and promote a new stable savanna woodland community}, journal = {JOURNAL OF VEGETATION SCIENCE}, volume = {32}, year = {2021}, month = {11/2021}, pages = {e13101}, abstract = {

Questions Species defined as ecosystem engineers (e.g. elephant) are able to strongly shape their habitat. In African savannas, elephants have often been shown to reduce woody-plant abundance and diversity. However, recent studies highlight more complex elephant-induced effects on vegetation. Here, we assessed if long-term high elephant densities (\>2 km(-2)) in a large open landscape resulted in the depletion of savanna woodland woody communities or if it led to a new alternative equilibrium. Location Woodland savanna of Hwange National Park, Zimbabwe. Elephant densities at the study site have remained high for the past two decades (\>2 km(-)(2)). Methods We measured long-term (\>15 years) elephant utilisation of woody-plant communities and their effects on vegetation structure, species composition and functional traits (e.g. N leaf concentration, specific leaf area) in 12 vegetation plots. Results We observed opportunistic foraging behaviour by elephants with only a slight temporal shift in species composition, mainly explained by changes in rare species. Further, we did not observe any modification in mean functional trait values, overall height, and stem diameters of the woody-plant communities. However, we found differential changes in woody-plant abundance according to the height layer (decrease in the number of tall plants [\>200 cm] and increase in the number of short plants [\<50 cm]) and a strong reduction in crown diameter for plants in the 50-200 cm height class. Conclusion Our study strongly suggests that long-term high elephant densities have led to a stable state in savanna woodland vegetation in terms of plant community composition and their functional traits. However, high elephant densities did affect vegetation structure, which would have several important indirect effects on this ecosystem (e.g. predator-prey interactions). We hope that this study stimulates more work on the long-term effects of ecosystem engineers in large and open ecosystems.

}, doi = {10.1111/jvs.13101}, author = {Ferry, Nicolas and Dray, Stephane and Fritz, Herv{\'e} and Ipavec, Audrey and Wigley, Benjamin J. and Charles-Dominique, Tristan and Bourgarel, Mathieu and Sebele, Lovelater and Valeix, Marion} } @article {88406, title = {The Lys 280 ➔ Gln mutation mimicking disease-linked acetylation of Lys 280 in tau extends the structural core of fibrils and modulates their catalytic properties.}, journal = {Protein Sci}, year = {2021}, month = {2021 Jan 25}, abstract = {

Amyloid fibrillar aggregates isolated from the brains of patients with neurodegenerative diseases invariably have post-translational modifications (PTMs). The roles that PTMs play in modulating the structures and polymorphism of amyloid aggregates, and hence their ability to catalyze the conversion of monomeric protein to their fibrillar structure is, however, poorly understood. This is particularly true in the case of tau aggregates, where specific folds of fibrillar tau have been implicated in specific tauopathies. Several PTMs, including acetylation at Lys 280, increase aggregation of tau in the brain, and increase neurodegeneration. In this study, tau-K18 K280Q, in which the Lys 280 ➔ Gln mutation is used to mimic acetylation at Lys 280, is shown, using HX-MS measurements, to form fibrils with a structural core that is longer than that of tau-K18 fibrils. Measurements of critical concentrations show that the binding affinity of monomeric tau-K18 for its fibrillar counterpart is only marginally more than that of monomeric tau-K18 K280Q for its fibrillar counterpart. Quantitative analysis of the kinetics of seeded aggregation, using a simple Michaelis-Menten-like model, in which the monomer first binds and then undergoes conformational conversion to β-strand, shows that the fibrils of tau-K18 K280Q convert monomeric protein more slowly than do fibrils of tau-K18. In contrast, monomeric tau-K18 K280Q is converted faster to fibrils than is monomeric tau-K18. Thus, the effect of Lys 280 acetylation on tau aggregate propagation in brain cells is expected to depend on the amount of acetylated tau present, and on whether the propagating seed is acetylated at Lys 280 or not. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.4030}, author = {Kumar, Harish and Udgaonkar, Jayant B} } @article {92421, title = {The Making of Long-Lasting Memories: A Fruit Fly Perspective.}, journal = {Front Behav Neurosci. }, volume = {15}, year = {2021}, month = {03/2021}, abstract = {

Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.

}, doi = {10.3389/fnbeh.2021.662129 }, author = {Roselli, C and Ramaswami, M and Boto, T and Cervantes-Sandoval, I} } @article {87967, title = {Mapping Distinct Sequences of Structure Formation Differentiating Multiple Folding Pathways of a Small Protein.}, journal = {J Am Chem Soc}, year = {2021}, month = {2021 Jan 12}, abstract = {

To determine experimentally how the multiple folding pathways of a protein differ, in the order in which the structural parts are assembled, has been a long-standing challenge. To resolve whether structure formation during folding can progress in multiple ways, the complex folding landscape of monellin has been characterized, structurally and temporally, using the multisite time-resolved FRET methodology. After an initial heterogeneous polypeptide chain collapse, structure formation proceeds on parallel pathways. Kinetic analysis of the population evolution data across various protein segments provides a clear structural distinction between the parallel pathways. The analysis leads to a phenomenological model that describes how and when discrete segments acquire structure independently of each other in different subensembles of protein molecules. When averaged over all molecules, structure formation is seen to progress as α-helix formation, followed by core consolidation, then β-sheet formation, and last end-to-end distance compaction. Parts of the protein that are closer in the primary sequence acquire structure before parts separated by longer sequence.

}, issn = {1520-5126}, doi = {10.1021/jacs.0c11097}, author = {Bhatia, Sandhya and Krishnamoorthy, Guruswamy and Udgaonkar, Jayant B} } @article {96411, title = {Mass spectrometric analysis of cyclotides from Clitoria ternatea: Xxx-Pro bond fragmentation as convenient diagnostic of Pro residue positioning.}, journal = {Chem Asian J}, year = {2021}, month = {2021 Jul 20}, abstract = {

Cyclotides, a class of macrocyclic plant peptides, characterized by a cyclic backbone and three inter-locking disulfide bonds, may be divided into two structural subfamilies, M{\"o}bius and Bracelet, based on presence or absence of a specific proline residue. The present study describes the suite of cyclotides obtained from Clitoria ternatea , characterized by LC-MS and MS/MS techniques. Notable variations in product ion distributions were observed in cyclotides belonging to different structural subfamilies based on the number and positions of proline residues. For instance, Cter M which is an abundant M{\"o}bius cyclotide in this plant containing three proline residues, displayed distinct b- and y- ion characteristics in the MS/MS spectra compared to Cliotide T1, another commonly identified cyclotide but belonging to the Bracelet subfamily having two proline residues. The distinct fragmentation pattern of prototypical cyclotides of each structural subfamily, determined by Xxx-Pro bond fragmentation, was used to rapidly identify and sequence a novel cyclotide ctr pep 30 from this plant.

}, issn = {1861-471X}, doi = {10.1002/asia.202100585}, author = {Venkatesan, Radhika and Balaram, Padmanabhan and Kalmankar, Neha V} } @article {91673, title = {Metabolome profiling reveals impact of water limitation on grain filling in contrasting rice genotypes.}, journal = {Plant Physiol Biochem}, volume = {162}, year = {2021}, month = {2021 Feb 25}, pages = {690-698}, abstract = {

Drought significantly decreases crop productivity, especially in high water consuming crops like rice. Grain filling is one of the important critical growth phases in rice and drought during this phase leads to significant reduction in yield. In this study, a comparison was made between IR64 (drought susceptible) and Apo (drought tolerant) rice genotypes to capture the response to water limitation (50\% field capacity (FC)) compared with the control (100\%FC) during grain filling. Plants were grown in a high-throughput phenomics facility for precise imposition of moisture stress during grain filling. Apo performed better in water limited conditions with lower reduction of photosynthetic rate and maintenance of lower leaf temperature than IR64. Days from sowing to maturity, spikelet fertility and seed weight were more impeded by water limitation in IR64 than in Apo. Unlike Apo, IR64 did not show any decrease in transpiration rate at 50\%FC compared with 100\%FC. Metabolomic profiling of spikelets at grain filling showed distinct effects of water limitation on accumulation of metabolites, especially in Apo. Secondary metabolism, mainly the phenylpropanoid pathway involved in scavenging mechanisms, was upregulated in Apo. Accumulation of most amino acids was significantly higher in IR64 than in Apo. Due to higher rates of photosynthesis under stress, most carbohydrates accumulated more in Apo than in IR64 at 50\%FC. Sucrose transporters were significantly upregulated in water limited conditions especially in Apo. Overall, thanks to higher source capacity, more source to sink transport and better scavenging, Apo showed a lower reduction in yield than IR64.

}, issn = {1873-2690}, doi = {10.1016/j.plaphy.2021.02.030}, author = {Vijayaraghavareddy, Preethi and Akula, Nagashree N and Vemanna, Ramu S and Math, Raviswamy G H and Shinde, Dhananjay D and Yin, Xinyou and Struik, Paul C and Makarla, Udayakumar and Sreeman, Sheshshayee} } @article {99931, title = {Microsecond dynamics during the binding-induced folding of an intrinsically disordered protein.}, journal = {J Mol Biol}, year = {2021}, month = {2021 Sep 16}, pages = {167254}, abstract = {

Tau is an intrinsically disordered protein implicated in many neurodegenerative diseases. The repeat domain fragment of tau, tau-K18, is known to undergo a disorder to order transition in the presence of lipid micelles and vesicles, in which helices form in each of the repeat domains. Here, the mechanism of helical structure formation, induced by a phospholipid mimetic, sodium dodecyl sulfate (SDS) at sub-micellar concentrations, has been studied using multiple biophysical probes. A study of the conformational dynamics of the disordered state, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS) has indicated the presence of an intermediate state, I, in equilibrium with the unfolded state, U. The cooperative binding of the ligand (L), SDS, to I has been shown to induce the formation of a compact, helical intermediate (IL) within the dead time (\~{}37 {\textmu}s) of a continuous flow mixer. Quantitative analysis of the PET-FCS data and the ensemble microsecond kinetic data, suggests that the mechanism of induction of helical structure can be described by a U <-> I <-> IL <-> FL mechanism, in which the final helical state, FL, forms from IL with a time constant of 50-200 {\textmu}s. Finally, it has been shown that the helical conformation is an aggregation-competent state that can directly form amyloid fibrils.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2021.167254}, author = {Sen, Sreemantee and Kumar, Harish and Udgaonkar, Jayant B} } @article {80093, title = {Microtubules provide guidance cues for myofibril and sarcomere assembly and growth.}, journal = {Dev Dyn}, volume = {250}, year = {2021}, month = {07/2020}, pages = {60-73}, abstract = {

BACKGROUND: Muscle myofibrils and sarcomeres present exceptional examples of highly ordered cytoskeletal filament arrays, whose distinct spatial organization is an essential aspect of muscle cell functionality. We utilized ultra-structural analysis to investigate the assembly of myofibrils and sarcomeres within developing myotubes of the indirect flight musculature of Drosophila.

RESULTS: A temporal sequence composed of three major processes was identified: subdivision of the unorganized cytoplasm of nascent, multi-nucleated myotubes into distinct organelle-rich and filament-rich domains; initial organization of the filament-rich domains into myofibrils harboring nascent sarcomeric units; and finally, maturation of the highly-ordered pattern of sarcomeric thick (myosin-based) and thin (microfilament-based) filament arrays in parallel to myofibril radial growth. Significantly, organized microtubule arrays were present throughout these stages and exhibited dynamic changes in their spatial patterns consistent with instructive roles. Genetic manipulations confirm these notions, and imply specific and critical guidance activities of the microtubule-based cytoskeleton, as well as structural interdependence between the myosin- and actin-based filament arrays.

CONCLUSIONS: Our observations highlight a surprisingly significant, behind-the-scenes role for microtubules in establishment of myofibril and sarcomere spatial patterns and size, and provide a detailed account of the interplay between major cytoskeletal elements in generating these essential contractile myogenic units. This article is protected by copyright. All rights reserved.

}, issn = {1097-0177}, doi = {10.1002/dvdy.227}, author = {Dhanyasi, Nagaraju and VijayRaghavan, K and Shilo, Ben-Zion and Schejter, Eyal D} } @article {92426, title = {Mitochondrial state determines functionally divergent stem cell population in planaria}, journal = {Stem Cell Reports}, year = {2021}, month = {04/2021}, abstract = {

Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared with their progenitors. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.

}, doi = {10.1016/j.stemcr.2021.03.022}, author = {Mohamed, Haroon M and Lakshmanan, V and Sarkar, Souradeep R and Lei, K and Vemula, PK and Palakodeti, D} } @article {90597, title = {Modulation of Immune Responses by Particle Size and Shape.}, journal = {Front Immunol}, volume = {607945}, year = {2021}, month = {2020}, abstract = {

The immune system has to cope with a wide range of irregularly shaped pathogens that can actively move (e.g., by flagella) and also dynamically remodel their shape (e.g., transition from yeast-shaped to hyphal fungi). The goal of this review is to draw general conclusions of how the size and geometry of a pathogen affect its uptake and processing by phagocytes of the immune system. We compared both theoretical and experimental studies with different cells, model particles, and pathogenic microbes (particularly fungi) showing that particle size, shape, rigidity, and surface roughness are important parameters for cellular uptake and subsequent immune responses, particularly inflammasome activation and T cell activation. Understanding how the physical properties of particles affect immune responses can aid the design of better vaccines.

}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.607945}, author = {Baranov, Maksim V and Kumar, Manoj and Sacanna, Stefano and Thutupalli, Shashi and van den Bogaart, Geert} } @article {87089, title = {The molecular mechanism of domain-swapping of the C-terminal domain of the SARS coronavirus main protease}, journal = {Biophys J}, volume = {120}, year = {2021}, month = {12/2020}, pages = {504-516}, abstract = {

In 3D-domain-swapping, two protein monomers exchange a part of their structures to form an intertwined homodimer, whose subunits resemble the monomer. Several viral proteins domain-swap to increase their structural complexity or functional avidity. The main protease (Mpro) of the SARS coronavirus proteolyzes viral polyproteins and has been a target for anti-SARS drug design. Domain-swapping in the α-helical C-terminal domain of Mpro (MproC) locks Mpro into a hyperactive octameric form which is hypothesized to promote the early stages of viral replication. However, in the absence of a complete molecular understanding of the mechanism of domain-swapping, investigations into the biological relevance of this octameric Mpro have stalled. Isolated MproC can exist as a monomer or a domain-swapped dimer. Here, we investigate the mechanism of domain-swapping of MproC using coarse-grained structure-based models and molecular dynamics simulations. Our simulations recapitulate several experimental features of MproC folding. Further, we find that a contact between a tryptophan in the MproC domain-swapping hinge and an arginine elsewhere forms early during folding, modulates the folding route and promotes domain-swapping to the native structure. An examination of the sequence and the structure of the tryptophan containing hinge loop shows that it has a propensity to form multiple secondary structures and contacts, indicating that it could be stabilized into either the monomer- or dimer-promoting conformations by mutations or ligand binding. Finally, since all residues in the tryptophan loop are identical in SARS-CoV and SARS-CoV-2, mutations that modulate domain-swapping may provide insights into the role of octameric Mpro in the early stage viral replication of both viruses.

}, doi = {10.1016/j.bpj.2020.11.2277}, author = {Terse, VL and Gosavi, S} } @article {96415, title = {A molecular sensor for cholesterol in the human serotonin receptor.}, journal = {Sci Adv}, volume = {7}, year = {2021}, month = {2021 Jul}, abstract = {

The function of several G protein-coupled receptors (GPCRs) exhibits cholesterol sensitivity. Cholesterol sensitivity of GPCRs could be attributed to specific sequence and structural features, such as the cholesterol recognition/interaction amino acid consensus (CRAC) motif, that facilitate their cholesterol-receptor interaction. In this work, we explored the molecular basis of cholesterol sensitivity exhibited by the serotonin receptor, the most studied GPCR in the context of cholesterol sensitivity, by generating mutants of key residues in CRAC motifs in transmembrane helix 2 (TM2) and TM5 of the receptor. Our results show that a lysine residue (K101) in one of the CRAC motifs is crucial for sensing altered membrane cholesterol levels. Insights from all-atom molecular dynamics simulations showed that cholesterol-sensitive functional states of the serotonin receptor are associated with reduced conformational dynamics of extracellular loops of the receptor. These results constitute one of the first reports on the molecular mechanism underlying cholesterol sensitivity of GPCRs.

}, issn = {2375-2548}, doi = {10.1126/sciadv.abh2922}, author = {Kumar, G Aditya and Sarkar, Parijat and Stepniewski, Tomasz Maciej and Jafurulla, Md and Singh, Shishu Pal and Selent, Jana and Chattopadhyay, Amitabha} } @article {95776, title = {The molecular systematics and diversification of a taxonomically unstable group of Asian cicada tribes related to Cicadini Latreille, 1802 (Hemiptera : Cicadidae)}, journal = {INVERTEBRATE SYSTEMATICS}, year = {2021}, month = {06/2021}, abstract = {

The cicadas (Hemiptera: Cicadidae) related to tribe Cicadini exhibit some of the most remarkable phenotypes in the family, with many genera possessing striking colour patterns and unusual morphological features. This largely Asian group of 13 tribes has proven challenging for cicada taxonomists, in part because of likely convergent evolution or losses of these phenotypes. We present the first focused molecular phylogeny of this clade, including similar to 60 described genera. The genetic dataset contains 839 ingroup-informative sites (out of 2575) from mitochondrial cytochrome c oxidase subunit I, nuclear elongation factor-1 alpha, and nuclear acetyltransferase. We use Bayesian and maximum likelihood trees to test recent changes in tribe- and subtribe- level classification, and we reconstruct ancestral character states for potentially convergent traits influencing tribe descriptions. We use fossil and molecular clock calibrations to estimate the temporal and geographic context of the radiation. The tribes Gaeanini, Leptopsaltriini, Platypleurini, Psithyristriini, and Tosenini appear polyphyletic and in need of revision, in part because of convergent evolution of opaque wings and multiple convergent gains or losses of abdominal tubercles. Kalabita Moulton, 1923 is transferred from Platypleurini to Leptopsaltriini. Vittagaeana gen. nov. is established for Vittagaeana paviei comb. nov. and Vittagaeana dives comb. nov., formerly in Tosena. Sinosenini syn. nov. is synonymised with Dundubiina. Ayuthiini trib. nov. is established with two new subtribes for Ayuthia Distant, 1919 and Distantalna Boulard, 2009, formerly in Tosenini. For the earliest split in the tree, one common ancestor appears to have been Indian + Asian in geographic distribution and the other Asian. We estimate that the radiation began in the middle Cenozoic Era, possibly as recently as the early Miocene. The recent and steady pattern of diversification suggests that refinement of tribe diagnoses will prove challenging.

}, doi = {10.1071/IS20079}, author = {Hill, Kathy B. R. and Marshall, David C and Marathe, Kiran and Moulds, Maxwell S. and Lee, Young June and Pham, Thai-Hong and Mohagan, Alma B. and Sarkar, Vivek and Price, Benjamin W. and Duffels, J. P. and Schouten, Marieke A. and de Boer, Arnold J. and Kunte, Krushnamegh and Simon, Chris} } @article {92880, title = {Monsoon forced evolution of savanna and the spread of agro-pastoralism in peninsular India.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 Apr 27}, pages = {9032}, abstract = {

An unresolved issue in the vegetation ecology of the Indian subcontinent is whether its savannas, characterized by relatively open formations of deciduous trees in C-grass dominated understories, are natural or anthropogenic. Historically, these ecosystems have widely been regarded as anthropogenic-derived, degraded descendants of deciduous forests. Despite recent work showing that modern savannas in the subcontinent fall within established bioclimatic envelopes of extant savannas elsewhere, the debate persists, at least in part because the regions where savannas occur also have a long history of human presence and habitat modification. Here we show for the first time, using multiple proxies for vegetation, climate and disturbances from high-resolution, well-dated lake sediments from Lonar Crater in peninsular India, that neither anthropogenic impact nor fire regime shifts, but monsoon weakening during the past ~ 6.0\ kyr\ cal. BP, drove the expansion of savanna at the expense of forests in peninsular India. Our results provide unambiguous evidence for a climate-induced origin and spread of the modern savannas of peninsular India at around the mid-Holocene. We further propose that this savannization preceded and drove the introduction of agriculture and development of sedentism in this region, rather than vice-versa as has often been assumed.

}, issn = {2045-2322}, doi = {10.1038/s41598-021-88550-8}, author = {Riedel, Nils and Fuller, Dorian Q and Marwan, Norbert and Poretschkin, Constantin and Basavaiah, Nathani and Menzel, Philip and Ratnam, Jayashree and Prasad, Sushma and Sachse, Dirk and Sankaran, Mahesh and Sarkar, Saswati and Stebich, Martina} } @article {103922, title = {A monster of a disease.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Dec 13}, abstract = {

When compulsions and obsessive thoughts took over her world, a graduate student found strength in her identity as a scientist.

}, issn = {2050-084X}, doi = {10.7554/eLife.75862}, author = {Sitaraman, Sahana} } @article {96410, title = {mRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence and activation.}, journal = {Skelet Muscle}, volume = {11}, year = {2021}, month = {2021 Jul 08}, pages = {18}, abstract = {

BACKGROUND: During skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation.

METHODS: Using isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells.

RESULTS: Quiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1 mice exhibit defective proliferation, and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies during primary MuSC activation on myofibers, with Fmrp puncta prominent in quiescence, but Dcp1a puncta appearing during activation/proliferation. This reciprocal expression of Fmrp and Dcp1a puncta is recapitulated in a C2C12 culture model of quiescence and activation: consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta.

CONCLUSIONS: Taken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.

}, issn = {2044-5040}, doi = {10.1186/s13395-021-00270-9}, author = {Roy, Nainita and Sundar, Swetha and Pillai, Malini and Patell-Socha, Farah and Ganesh, Sravya and Aloysius, Ajoy and Rumman, Mohammed and Gala, Hardik and Hughes, Simon M and Zammit, Peter S and Dhawan, Jyotsna} } @article {98081, title = {Mycobacterium tuberculosis SufR responds to nitric oxide via its 4Fe-4S cluster and regulates Fe-S cluster biogenesis for persistence in mice.}, journal = {Redox Biol}, volume = {46}, year = {2021}, month = {2021 Jul 02}, pages = {102062}, abstract = {

The persistence of Mycobacterium tuberculosis (Mtb) is a major problem in managing tuberculosis (TB). Host-generated nitric oxide (NO) is perceived as one of the signals by Mtb to reprogram metabolism and respiration for persistence. However, the mechanisms involved in NO sensing and reorganizing Mtb{\textquoteright}s physiology are not fully understood. Since NO damages iron-sulfur (Fe-S) clusters of essential enzymes, the mechanism(s) involved in regulating Fe-S cluster biogenesis could help Mtb persist in host tissues. Here, we show that a transcription factor SufR (Rv1460) senses NO via its 4Fe-4S cluster and promotes persistence of Mtb by mobilizing the Fe-S cluster biogenesis system; suf operon (Rv1460-Rv1466). Analysis of anaerobically purified SufR by UV-visible spectroscopy, circular dichroism, and iron-sulfide estimation confirms the presence of a 4Fe-4S cluster. Atmospheric O and HO gradually degrade the 4Fe-4S cluster of SufR. Furthermore, electron paramagnetic resonance (EPR) analysis demonstrates that NO directly targets SufR 4Fe-4S cluster by forming a protein-bound dinitrosyl-iron-dithiol complex. DNase I footprinting, gel-shift, and in vitro transcription assays confirm that SufR directly regulates the expression of the suf operon in response to NO. Consistent with this, RNA-sequencing of MtbΔsufR demonstrates deregulation of the suf operon under NO stress. Strikingly, NO inflicted irreversible damage upon Fe-S clusters to exhaust respiratory and redox buffering capacity of MtbΔsufR. Lastly, MtbΔsufR failed to recover from a NO-induced non-growing state and displayed persistence defect inside immune-activated macrophages and murine lungs in a NO-dependent manner. Data suggest that SufR is a sensor of NO that supports persistence by reprogramming Fe-S cluster metabolism and bioenergetics.

}, issn = {2213-2317}, doi = {10.1016/j.redox.2021.102062}, author = {Anand, Kushi and Tripathi, Ashutosh and Shukla, Kaustubh and Malhotra, Nitish and Jamithireddy, Anil Kumar and Jha, Rajiv Kumar and Chaudhury, Susmit Narayan and Rajmani, Raju S and Ramesh, Arati and Nagaraja, Valakunja and Gopal, Balasubramanian and Nagaraju, Ganesh and Narain Seshayee, Aswin Sai and Singh, Amit} } @article {95780, title = {Natural and unnatural history of the coronavirus: The uncertain path to the pandemic}, journal = {CURRENT SCIENCE}, volume = {120}, year = {2021}, month = {06/2021}, pages = {1820-1826}, chapter = {2}, abstract = {

There is currently an ongoing debate on the origins of the SARS-CoV-2 coronavirus, the causative agent of the COVID-19 pandemic. The hypothesis that the virus emerged as a result of natural zoonotic transfer has been controversially questioned, on the basis of unusual sequence signatures in the spike protein and the absence of evidence for an intermediate animal host. This article briefly surveys the background to coronavirus research and addresses the development of the methods of gain of function research, which have been suggested to be a potential public health threat in the event of laboratory leakage.

}, doi = {10.18520/cs/v120/i12/1820-1826}, author = {Balaram, P.} } @article {99326, title = {NEDD8 Deamidation Inhibits Cullin RING Ligase Dynamics.}, journal = {Front Immunol}, volume = {12}, year = {2021}, month = {2021}, pages = {695331}, abstract = {

Cullin-RING ligases (CRLs) are a significant subset of Ubiquitin E3 ligases that regulate multiple cellular substrates involved in innate immunity, cytoskeleton modeling, and cell cycle. The glutamine deamidase Cycle inhibitory factor (Cif) from enteric bacteria inactivates CRLs to modulate these processes in the host cell. The covalent attachment of a Ubiquitin-like protein NEDD8 catalytically activates CRLs by driving conformational changes in the Cullin C-terminal domain (CTD). NEDDylation results in a shift from a compact to an open CTD conformation through non-covalent interactions between NEDD8 and the WHB subdomain of CTD, eliminating the latter{\textquoteright}s inhibitory interactions with the RING E3 ligase-Rbx1/2. It is unknown whether the non-covalent interactions are sufficient to stabilize Cullin CTD{\textquoteright}s catalytic conformation. We studied the dynamics of Cullin-CTD in the presence and absence of NEDD8 using atomistic molecular dynamics (MD) simulations. We uncovered that NEDD8 engages in non-covalent interactions with 4HB/αβ subdomains in Cullin-CTD to promote open conformations. Cif deamidates glutamine 40 in NEDD8 to inhibit the conformational change in CRLs by an unknown mechanism. We investigated the effect of glutamine deamidation on NEDD8 and its interaction with the WHB subdomain post-NEDDylation using MD simulations and NMR spectroscopy. Our results suggest that deamidation creates a new intramolecular salt bridge in NEDD8 to destabilize the NEDD8/WHB complex and reduce CRL activity.

}, issn = {1664-3224}, doi = {10.3389/fimmu.2021.695331}, author = {Mohanty, Priyesh and Chatterjee, Kiran Sankar and Das, Ranabir} } @article {96101, title = {Negative effects of nitrogen override positive effects of phosphorus on grassland legumes worldwide.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Jul 13}, abstract = {

Anthropogenic nutrient enrichment is driving global biodiversity decline and modifying ecosystem functions. Theory suggests that plant functional types that fix atmospheric nitrogen have a competitive advantage in nitrogen-poor soils, but lose this advantage with increasing nitrogen supply. By contrast, the addition of phosphorus, potassium, and other nutrients may benefit such species in low-nutrient environments by enhancing their nitrogen-fixing capacity. We present a global-scale experiment confirming these predictions for nitrogen-fixing legumes (Fabaceae) across 45 grasslands on six continents. Nitrogen addition reduced legume cover, richness, and biomass, particularly in nitrogen-poor soils, while cover of non-nitrogen-fixing plants increased. The addition of phosphorous, potassium, and other nutrients enhanced legume abundance, but did not mitigate the negative effects of nitrogen addition. Increasing nitrogen supply thus has the potential to decrease the diversity and abundance of grassland legumes worldwide regardless of the availability of other nutrients, with consequences for biodiversity, food webs, ecosystem resilience, and genetic improvement of protein-rich agricultural plant species.

}, issn = {1091-6490}, doi = {10.1073/pnas.2023718118}, author = {Tognetti, Pedro M and Prober, Suzanne M and B{\'a}ez, Selene and Chaneton, Enrique J and Firn, Jennifer and Risch, Anita C and Schuetz, Martin and Simonsen, Anna K and Yahdjian, Laura and Borer, Elizabeth T and Seabloom, Eric W and Arnillas, Carlos Alberto and Bakker, Jonathan D and Brown, Cynthia S and Cadotte, Marc W and Caldeira, Maria C and Daleo, Pedro and Dwyer, John M and Fay, Philip A and Gherardi, Laureano A and Hagenah, Nicole and Hautier, Yann and Komatsu, Kimberly J and McCulley, Rebecca L and Price, Jodi N and Standish, Rachel J and Stevens, Carly J and Wragg, Peter D and Sankaran, Mahesh} } @article {92881, title = {Nesting ecology does not explain slow-fast cognitive differences among honeybee species.}, journal = {Anim Cogn}, year = {2021}, month = {2021 Apr 27}, abstract = {

Slow-fast behavioral and life history differences have been tied to slow-fast variation in cognition that is part of the general speed-accuracy tradeoff. While there is growing evidence for such cognitive variation and its association with behavior and life history at the intraspecific level, it is unknown if a similar relationship extends to the interspecific level. Since interspecific differences in cognition have been shown to be a function of ecology and life history, such differences should be reflected in multiple traits that comprise the slow-fast cognitive axis. In this study, by measuring multiple cognitive traits in individuals, we tested for differences in the cognitive phenotype among four honeybee species, which differ in their behavior and life history in a manner that is associated with differences in their nesting ecology. Our results indicate that a set of cognitive traits consistently covary within each species, resulting in slow and fast cognitive phenotypes that largely meet the predictions of the speed-accuracy tradeoff. We also find that the four species group into two distinct clusters on a slow-fast cognitive axis, although their positions do not align with the known differences in their life history and nesting ecology. We instead find that cognitive differences among the four species are correlated with their brain size. We discuss the possible implications of these results for the role of ecology on slow-fast cognitive differences and the evolution of cognition.

}, issn = {1435-9456}, doi = {10.1007/s10071-021-01515-2}, author = {Tait, Catherine and Brockmann, Axel and Naug, Dhruba} } @article {93662, title = {A new baviine species of the genus Maripanthus Maddison from India (Araneae: Salticidae)}, journal = {REVUE SUISSE DE ZOOLOGIE}, volume = {128}, year = {2021}, month = {03/2021}, pages = {199-205}, abstract = {

A new species of the genus Maripanthus Maddison, 2020, M. gloria Caleb, sp. nov. (male female) is diagnosed and described from the Karnataka State of India. A map showing the distributional records of all known congeners is provided.

}, doi = {10.35929/RSZ.0045}, author = {Caleb, John T. D. and Francis, Clement and Bhat, Vijay Krishna} } @article {95319, title = {A new medium-sized rupicolous Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) of the C. bangara clade from granite boulder habitats in Krishnagiri, Tamil Nadu, India.}, journal = {Zootaxa}, volume = {4969}, year = {2021}, month = {2021 May 11}, pages = {351366}, abstract = {

We describe a new species of the Cnemaspis bangara clade from a rocky hillock near Kugai Periya Mariamman Temple, Krishnagiri fort, Krishnagiri District of Tamil Nadu, India. Cnemaspis krishnagiriensis sp. nov. can be diagnosed from all other peninsular Indian congeners by its medium body size (maximum SVL 40 mm), heterogeneous dorsal pholidosis, spine-like tubercles absent on flanks; presence of four femoral pores on each thigh separated on either side by nine or 10 poreless scales from three continuous precloacal pores in males; tail with enlarged, strongly keeled, conical tubercles forming four whorls on anterior portion, six tubercles in first whorl, four tubercles in second to fourth whorls, enlarged tubercles restricted to only paravertebral region on rest of the tail; median row of sub-caudals smooth and distinctly enlarged, and a unique colour pattern. The new species can be diagnosed from members of C. bangara clade by the number of dorsal tubercles rows at mid-body, the number of enlarged tubercles in paravertebral rows, the number of ventral scales across belly at mid-body, the number longitudinal ventral scales from mental to cloaca, the number of femoral and precloacal pores and poreless scales separating these series, and subtle colour pattern differences; besides 9.217.6 \% uncorrected ND2 sequence divergence. Cnemaspis krishnagiriensis sp. nov. is the fourth member of the recently described bangara clade and is the first that is known to be distributed \<900 m asl.. The discovery of yet another endemic species of Cnemaspis from lower elevations of the Mysore Plateau once again highlights the need of dedicated systematic sampling to uncover the true diversity of Cnemaspis. We also address a nomenclatural issue related to the recently described Cnemaspis stellapulvis Khandekar, Thackeray Agarwal.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4969.2.7}, author = {Agarwal, Ishan and Thackeray, Tejas and Khandekar, Akshay} } @article {90470, title = {New Research Is Shining Light on How Collateral Arteries Form in the Heart: a Future Therapeutic Direction?}, journal = {Curr Cardiol Rep}, volume = {23}, year = {2021}, month = {2021 Mar 02}, pages = {30}, abstract = {

PURPOSE OF REVIEW: Collateral arteries create artery-artery anastomoses that could serve as natural bypasses that in the heart could relieve the various complications of ischemia heart disease. Recent work using animal models have begun to reveal details of how coronary collateral arteries form.

RECENT FINDINGS: Mouse genetics has been used to study the cellular and molecular mechanisms of collateral artery development. Collateral arteries are not pre-existing in the mouse heart, and only form in response to injury. Myocardial infarction creates tissue hypoxia that triggers the expression of growth factors and chemokines that guide collaterogenesis. Collateral development is more robust in neonatal hearts when compared with adults, and contributes to neonatal heart regeneration. The identification of signaling pathways and cellular responses underlying coronary collateral artery development suggests potential translational strategies. Continued investigation into this subject could lead to the identification of targetable pathways that induce collateral arteries for cardiac revascularization.

}, issn = {1534-3170}, doi = {10.1007/s11886-021-01460-z}, author = {Red-Horse, Kristy and Das, Soumyashree} } @article {92879, title = {A new small-bodied, polymorphic emCnemaspis/em Strauch, 1887 (Squamata: Gekkonidae) allied to emC. monticola/em Manamendra-Arachchi, Batuwita amp; Pethiyagoda, 2007 from the Central Western Ghats of Karnataka, India.}, journal = {Zootaxa}, volume = {4950}, year = {2021}, month = {2021 Mar 31}, pages = {zootaxa.4950.3.5}, abstract = {

We describe a new small-bodied, polymorphic Cnemaspis from near Hongadahalla village, Sakleshpur in the Central Western Ghats of Karnataka, India. Cnemaspis schalleri sp. nov. is allied to C. monticola and can be diagnosed from all other Indian Cnemaspis by its small body size; presence of spine-like tubercles on flank; heterogeneous dorsal pholidosis; presence of both precloacal and femoral pores in males; dorsal pholidosis of tail heterogeneous, composed of small, weakly keeled, flattened, sub-imbricate scales intermixed with enlarged, strongly keeled, distinctly pointed, conical tubercles forming whorls; slightly enlarged median row of sub-caudal scales, smooth at anterior half and strongly keeled posteriorly. The new species differs from C. monticola based on the number of dorsal tubercle rows at mid-body, the number of paravertebral tubercles, the number of precloacal pores and poreless scales between precloacal and femoral pores; besides 8.9-10.7 \% uncorrected ND2 sequence divergence. We also provide the first description of topotypic males of C. monticola along with the first data on live colouration and natural history. Cnemaspis schalleri sp. nov. is the second new Cnemaspis described from around Sakleshpur within a span of less than a year with minimal field survey effort. It is almost certain than the dedicated systematic sampling across the Central Western Ghats will result in the discovery of many undescribed Cnemaspis lineages.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4950.3.5}, author = {Khandekar, Akshay and Thackeray, Tejas and Agarwal, Ishan} } @article {104887, title = {A new species of geckos of the genus Cyrtodactylus Gray, 1827 from Arunachal Pradesh, India}, journal = {Evolutionary Systematics}, volume = {5}, year = {2021}, month = {01/2021}, pages = {13-23}, abstract = {

We here describe a new species of bent-toed geckos from the northeastern Indian state of Arunachal Pradesh, which is widespread across the Dafla and Mishmi hills, occurring at elevations ranging from 179 m to 1400 m. The new species is recovered as sister to the Cyrtodactylus khasiensis clade based on a molecular phylogeny inferred from mitochondrial NADH-ubiquinone oxidoreductase, subunit 2 gene. Intraspecific uncorrected pairwise sequence divergence (p-distance) for the new species was found to be between 0 and 5\%, whereas the interspecific divergence from the closely-related congeners was between 19 and 30\%. The new species can be differentiated from members of the C. khasiensis clade using a suite of morphological characters: moderate body size (SVL 64.9{\textendash}81.7); 8{\textendash}11 supralabials; 8{\textendash}10 infralabials; 24{\textendash}26 bluntly conical, feebly keeled dorsal tubercles; 50{\textendash}60 paravertebral tubercles; ~38 ventral scales between ventrolateral folds; no precloacal groves; 6{\textendash}10 precloacofemoral pores in a continuous series; 10{\textendash}16 distal subdigital lamellae on IV of pes; subcaudal scalation of original tail without enlarged plates. This is the fourth reptile species described from Arunachal Pradesh from the expedition led by the team, and this further highlights the need for further herpetological investigations into the region.

}, doi = {10.3897/evolsyst.5.61667}, author = {Mirza, Zeeshan A and Harshal Bhosale and Ansari, Faizan and Phansalkar, Pushkar and Sawant, Mandar and Gowande, Gaurang and Patel, Harshil} } @article {104891, title = {A new species of snake of the genus Oligodon Boie in Fitzinger, 1826 (Reptilia, Serpentes) from the Western Himalayas}, journal = {Evolutionary Systematics}, volume = {5}, year = {2021}, month = {11/2021}, pages = {335-345 }, abstract = {

A new species of Oligodon Fitzinger, 1826 is described based on specimens collected from Churah Valley of Himachal Pradesh. The new species is related to O. arnensis based on molecular as well as morphological data, however differs from it in several aspects. The new species shows a pairwise sequence divergence of 6{\textendash}20\% from congeners for mitochondrial cytochrome b gene. Lack of pterygoid and palatine teeth of the new species suggests that the diet may largely comprise of eggs. Discovery of the new species is not surprising, as the Western Himalayas has been poorly explored in terms of its herpetofaunal diversity. Considerable genetic divergence in the sampled sequence suggests Oligodon arnensis is a species complex, likely represents multiple species and a revision of the group would be desirable.

}, doi = {10.3897/evolsyst.5.72564 }, author = {Mirza, Zeeshan A and Bhardwaj, Virender Kumar and Patel, Harshil} } @article {103920, title = {A new species of Zographetus Watson, 1893 (Lepidoptera: Hesperiidae) from Sikkim, eastern Himalaya, India}, journal = {ZOOTAXA }, volume = {5072}, year = {2021}, month = {12/2021}, pages = {373-379}, abstract = {

A new species, Zographetus dzonguensis sp. nov., is described based on three male specimens from Upper Dzongu, North Sikkim District, Sikkim, India. The new species is closely similar to Z. pangi from Guangdong and Z. hainanensis from Hainan, China, from which it is distinguished based on the following combination of external characters: (a) forewing with the white spot at the base of space M3 being sharply pointed at the inner edge and conspicuously more elongated, and (b) on underside of hindwing, all chocolate-brown spots being smaller, in Z. dzonguensis sp. nov. compared with both Z. pangi and Z. hainanensis. In Z. dzonguensis sp. nov., the male genitalia may be distinguished as follows: (c) tegumen and uncus are almost equal in length, (d) the dorsal outline of tegumen is relatively flat, and (e) saccus is distinctly bent upward as angle between vinculum and saccus is more acute than in Z. pangi and Z. hainanensis.

}, doi = {10.11646/zootaxa.5072.4.4}, author = {Karmakar, Tarun and Lepcha, Sonam Wangchuk and Basu, Dipendra Nath and Kunte, Krushnamegh} } @article {93673, title = {Non-covalent Interaction With SUMO Enhances the Activity of Human Cytomegalovirus Protein IE1}, journal = {Front. Cell Dev. Biol.}, year = {2021}, month = {05/2021}, abstract = {

Viruses interact with the host cellular pathways to optimize cellular conditions for replication. The Human Cytomegalovirus (HCMV) Immediate-Early protein 1 (IE1) is the first viral protein to express during infection. It is a multifunctional and conditionally essential protein for HCMV infection. SUMO signaling regulates several cellular pathways that are also targets of IE1. Consequently, IE1 exploits SUMO signaling to regulate these pathways. The covalent interaction of IE1 and SUMO (IE1-SUMOylation) is well studied. However, the non-covalent interactions between SUMO and IE1 are unknown. We report two SUMO-Interacting Motifs (SIMs) in IE1, one at the end of the core domain and another in the C-terminal domain. NMR titrations showed that IE1-SIMs bind to SUMO1 but not SUMO2. Two critical functions of IE1 are inhibition of SUMOylation of Promyelocytic leukemia protein (PML) and transactivation of viral promoters. Although the non-covalent interaction of IE1 and SUMO is not involved in the inhibition of PML SUMOylation, it contributes to the transactivation activity. The transactivation activity of IE1 was previously correlated to its ability to inhibit PML SUMOylation. Our results suggest that transactivation and inhibition of PML SUMOylation are independent activities of IE1.

}, doi = {10.3389/fcell.2021.662522}, author = {Tripathi, Vasvi and Chatterjee, Kiran Sankar and Das, Ranabir} } @article {95782, title = {Novel insights in plasticity and learning impairments in Fragile X Syndrome.}, journal = {Brain Res Bull}, year = {2021}, month = {2021 Jul 07}, abstract = {

The function of brain circuits relies on high-fidelity information transfer, precisely controlling integration of synaptic input, leading to neuronal output. Synaptic inputs arrive primarily at dendrites, where they undergo integration and summation throughout the somatodendritic domain, ultimately leading to axonal output. Emerging evidence suggests that the ability of neurons to transfer synaptic information and modulate their output is impaired in the neurodevelopmental disorder Fragile X Syndrome. Indeed, how neurons may or may not respond to sensory information during development that leads to compensation of their activity appears to be a salient feature of rodent models of Fragile X Syndrome. In this review we summarise recent findings that have shone light on the ability of neurons in sensory and limbic circuits to reliably code information. We highlight which aspects of this transform are underlain by either direct loss of FMRP in Fragile X Syndrome and which likely result from compensatory or homeostatic alterations to neuron function. Dissection of these mechanisms effect on neuronal plasticity throughout development will have direct implications for individuals with Fragile X Syndrome, directing the timing and duration of different treatment options.

}, issn = {1873-2747}, doi = {10.1016/j.brainresbull.2021.06.025}, author = {Booker, Sam A and Kind, Peter C} } @article {84571, title = {A novel monopartite begomovirus and satellites associated with yellow mosaic disease of Sida spp. in India.}, journal = {Arch Virol}, volume = {166}, year = {2021}, month = {2020 Oct 17}, pages = {299-302}, abstract = {

Begomoviruses (family Geminiviridae) cause severe diseases in many economically important crops and non-cultivated plants in the warmer regions of the world. Non-cultivated weeds have been reported to act as natural virus reservoirs. In January 2016, Sida plants with yellow mosaic symptoms were found at the edge of an agricultural field in Gujarat, India. Sequence analysis of the viral genomic components cloned from a diseased Sida plant indicated the presence of a distinct monopartite begomovirus (proposed as sida yellow mosaic Gujarat virus) along with a betasatellite (ludwigia leaf distortion betasatellite) and an alphasatellite (malvastrum yellow mosaic alphasatellite). Our results emphasize that this weed may harbor a begomovirus-alphasatellite-betasatellite complex. This host serves as a potential source of virus inoculum, which can be transmitted by whiteflies to other cultivated crops.

}, issn = {1432-8798}, doi = {10.1007/s00705-020-04843-9}, author = {Chahwala, Fenisha D and Singh, Dhananjay and Kumar, R Vinoth and Rathore, Sangeeta and Yadav, Brijesh K and Singh, Bijendra and Singh, Achuit K} } @article {94155, title = {Nutrient deposition enhances post-fire survival in non-N-fixing savanna tree seedlings}, journal = {JOURNAL OF VEGETATION SCIENCE}, volume = {32}, year = {2021}, month = {03/2021}, pages = {e13020}, abstract = {

Questions Nutrient deposition can modify plant growth and potentially alter the susceptibility of plants to disturbance events, while simultaneously influencing properties of the disturbance regimes themselves. With deposition rates accelerating, ecosystems such as savannas and tropical dry forests that are characterised by frequent disturbances such as fire, might be particularly sensitive to changes in nutrient availability. In these mixed tree-grass ecosystems, tree seedling growth rates strongly influence the ability of seedlings to survive fire, and hence, vegetation structure and tree community composition. However, the effects of nutrient deposition on the susceptibility of recruiting trees to fire remain poorly quantified. Here we ask: (a) how does nutrient deposition influence post-fire survival of tree seedlings, and hence, tree recruitment in savannas; and (b) whether the co-dominant functional groups (N-fixers and non-N-fixers) respond differently, signalling a potential for long-term changes in tree communities.

Location Savannas and tropical dry forests of India.

Methods In a field experiment, seedlings of four N-fixing and four non-N-fixing savanna tree species were grown for 18 months while exposed to a factorial combination of nitrogen (N) and phosphorus (P) addition. We quantified nutrient-mediated changes in mean seedling growth and growth of the fastest growing individuals. Seedlings were then exposed to a fire treatment at the end of 18 months, and post-fire seedling survival recorded after six months.

Results N-fixers showed substantially greater post-fire seedling survival compared to non-N-fixers in unfertilised treatments. Nutrient addition did not alter post-fire survival of N-fixers. However, fertilisation, especially with N, increased post-fire survival in non-N-fixers by increasing the growth of the fastest growing individuals.

Conclusions Nutrient deposition can dilute the relative advantage of N-fixing seedlings in terms of their post-fire survival, potentially leading to increased relative abundances of non-N-fixers in post-fire resprout communities, with long-term consequences for the composition of savanna tree communities.

}, doi = {10.1111/jvs.13020}, author = {Varma, Varun and Sankaran, Mahesh} } @article {102255, title = {Nutrient enrichment increases invertebrate herbivory and pathogen damage in grasslands}, journal = {JOURNAL OF ECOLOGY }, year = {2021}, type = {10/2021}, abstract = {

Plant damage by invertebrate herbivores and pathogens influences the dynamics of grassland ecosystems, but anthropogenic changes in nitrogen and phosphorus availability can modify these relationships. Using a globally distributed experiment, we describe leaf damage on 153 plant taxa from 27 grasslands worldwide, under ambient conditions and with experimentally elevated nitrogen and phosphorus. Invertebrate damage significantly increased with nitrogen addition, especially in grasses and non-leguminous forbs. Pathogen damage increased with nitrogen in grasses and legumes but not forbs. Effects of phosphorus were generally weaker. Damage was higher in grasslands with more precipitation, but climatic conditions did not change effects of nutrients on leaf damage. On average, invertebrate damage was relatively higher on legumes and pathogen damage was relatively higher on grasses. Community-weighted mean damage reflected these functional group patterns, with no effects of N on community-weighted pathogen damage (due to opposing responses of grasses and forbs) but stronger effects of N on community-weighted invertebrate damage (due to consistent responses of grasses and forbs). Synthesis. As human-induced inputs of nitrogen and phosphorus continue to increase, understanding their impacts on invertebrate and pathogen damage becomes increasingly important. Our results demonstrate that eutrophication frequently increases plant damage and that damage increases with precipitation across a wide array of grasslands. Invertebrate and pathogen damage in grasslands is likely to increase in the future, with potential consequences for plant, invertebrate and pathogen communities, as well as the transfer of energy and nutrients across trophic levels.

}, doi = {10.1111/1365-2745.13801}, author = {Ebeling, Anne and Strauss, Alex T. and Adler, Peter B. and Arnillas, Carlos A. and Barrio, Isabel C. and Biederman, Lori A. and Borer, Elizabeth T. and Bugalho, Miguel N. and Caldeira, Maria C. and Cadotte, Marc W. and Daleo, Pedro and Eisenhauer, Nico and Eskelinen, Anu and Fay, Philip A. and Firn, Jennifer and Graff, Pamela and Hagenah, Nicole and Haider, Sylvia and Komatsu, Kimberly J. and McCulley, Rebecca L. and Mitchell, Charles E. and Moore, Joslin L. and Pascual, Jesus and Peri, Pablo L. and Power, Sally A. and Prober, Suzanne M. and Risch, Anita C. and Roscher, Christiane and Sankaran, Mahesh and Seabloom, Eric W. and Schielzeth, Holger and Schuetz, Martin and Speziale, Karina L. and Tedder, Michelle and Virtanen, Risto and Blumenthal, Dana M.} } @article {103399, title = {Opposing community assembly patterns for dominant and jonnondominant plant species in herbaceous ecosystems globally}, journal = {ECOLOGY AND EVOLUTION }, year = {2021}, month = {11/02021}, abstract = {

Biotic and abiotic factors interact with dominant plants-the locally most frequent or with the largest coverage-and nondominant plants differently, partially because dominant plants modify the environment where nondominant plants grow. For instance, if dominant plants compete strongly, they will deplete most resources, forcing nondominant plants into a narrower niche space. Conversely, if dominant plants are constrained by the environment, they might not exhaust available resources but instead may ameliorate environmental stressors that usually limit nondominants. Hence, the nature of interactions among nondominant species could be modified by dominant species. Furthermore, these differences could translate into a disparity in the phylogenetic relatedness among dominants compared to the relatedness among nondominants. By estimating phylogenetic dispersion in 78 grasslands across five continents, we found that dominant species were clustered (e.g., co-dominant grasses), suggesting dominant species are likely organized by environmental filtering, and that nondominant species were either randomly assembled or overdispersed. Traits showed similar trends for those sites (\<50\%) with sufficient trait data. Furthermore, several lineages scattered in the phylogeny had more nondominant species than expected at random, suggesting that traits common in nondominants are phylogenetically conserved and have evolved multiple times. We also explored environmental drivers of the dominant/nondominant disparity. We found different assembly patterns for dominants and nondominants, consistent with asymmetries in assembly mechanisms. Among the different postulated mechanisms, our results suggest two complementary hypotheses seldom explored: (1) Nondominant species include lineages adapted to thrive in the environment generated by dominant species. (2) Even when dominant species reduce resources to nondominant ones, dominant species could have a stronger positive effect on some nondominants by ameliorating environmental stressors affecting them, than by depleting resources and increasing the environmental stress to those nondominants. These results show that the dominant/nondominant asymmetry has ecological and evolutionary consequences fundamental to understand plant communities.

}, doi = {10.1002/ece3.8266}, author = {Arnillas, Carlos Alberto and Borer, Elizabeth and Seabloom, Eric and Alberti, Juan and B{\'a}ez, Selene and Bakker, Jonathon and Boughton, Elizabeth and Buckley, Yvonne and Bugalho, Miguel Nuno and Donohue, Ian and Dwyer, John and Eskelinen, Anu and Firn, Jennifer and Gridzak, Riley and Hagenah, Nicole and Hautier, Yann and Helm, Aveliina and Jentsch, Anke and Knops, Johannes M. H. and Komatsu, Kimberly J. and Laanisto, Lauri and Laungani, Ramesh and McCulley, Rebecca and Moore, Joslin and Morgan, John and Peri, Pablo Luis and Power, Sally A. and Price, Jodi and Sankaran, Mahesh and Schamp, Brandon and Speziale, Karina and Standish, Rachel and Virtanen, Risto and Cadotte, Marc W.} } @article {105155, title = {Opposing community assembly patterns for dominant and nondominant plant species in herbaceous ecosystems globally.}, journal = {Ecol Evol}, volume = {11}, year = {2021}, month = {2021 Dec}, pages = {17744-17761}, abstract = {

Biotic and abiotic factors interact with dominant plants-the locally most frequent or with the largest coverage-and nondominant plants differently, partially because dominant plants modify the environment where nondominant plants grow. For instance, if dominant plants compete strongly, they will deplete most resources, forcing nondominant plants into a narrower niche space. Conversely, if dominant plants are constrained by the environment, they might not exhaust available resources but instead may ameliorate environmental stressors that usually limit nondominants. Hence, the nature of interactions among nondominant species could be modified by dominant species. Furthermore, these differences could translate into a disparity in the phylogenetic relatedness among dominants compared to the relatedness among nondominants. By estimating phylogenetic dispersion in 78\ grasslands across five continents, we found that dominant species were clustered (e.g., co-dominant grasses), suggesting dominant species are likely organized by environmental filtering, and that nondominant species were either randomly assembled or overdispersed. Traits showed similar trends for those sites (\<50\%) with sufficient trait data. Furthermore, several lineages scattered in the phylogeny had more nondominant species than expected at random, suggesting that traits common in nondominants are phylogenetically conserved and have evolved multiple times. We also explored environmental drivers of the dominant/nondominant disparity. We found different assembly patterns for dominants and nondominants, consistent with asymmetries in assembly mechanisms. Among the different postulated mechanisms, our results suggest two complementary hypotheses seldom explored: (1) Nondominant species include lineages adapted to thrive in the environment generated by dominant species. (2) Even when dominant species reduce resources to nondominant ones, dominant species could have a stronger positive effect on some nondominants by ameliorating environmental stressors affecting them, than by depleting resources and increasing the environmental stress to those nondominants. These results show that the dominant/nondominant asymmetry has ecological and evolutionary consequences fundamental to understand plant communities.

}, issn = {2045-7758}, doi = {10.1002/ece3.8266}, author = {Arnillas, Carlos Alberto and Borer, Elizabeth T and Seabloom, Eric W and Alberti, Juan and B{\'a}ez, Selene and Bakker, Jonathan D and Boughton, Elizabeth H and Buckley, Yvonne M and Bugalho, Miguel Nuno and Donohue, Ian and Dwyer, John and Firn, Jennifer and Gridzak, Riley and Hagenah, Nicole and Hautier, Yann and Helm, Aveliina and Jentsch, Anke and Knops, Johannes M H and Komatsu, Kimberly J and Laanisto, Lauri and Laungani, Ramesh and McCulley, Rebecca and Moore, Joslin L and Morgan, John W and Peri, Pablo Luis and Power, Sally A and Price, Jodi and Sankaran, Mahesh and Schamp, Brandon and Speziale, Karina and Standish, Rachel and Virtanen, Risto and Cadotte, Marc W} } @article {102257, title = {Optimized protocol to create deletion in adherent cell lines using CRISPR/Cas9 system.}, journal = {STAR Protoc}, volume = {2}, year = {2021}, month = {2021 Dec 17}, pages = {100857}, abstract = {

The CRISPR/Cas9 system is a powerful tool for genome editing and is adaptable for a wide range of applications. Here, we have put together a step-by-step protocol for generating knockout cell lines (coding or non-coding region) using CRISPR/Cas9 tool. The protocol below has been tested on adherent cell lines such as HeLa and MCF7. However, it may easily be adapted to other adherent cell lines with minor variations. For complete details on the use and execution of this protocol, please refer to Farooq et\ al. (2021).

}, issn = {2666-1667}, doi = {10.1016/j.xpro.2021.100857}, author = {Farooq, Umer and Notani, Dimple} } @article {96414, title = {Optimizing testing for COVID-19 in India.}, journal = {PLoS Comput Biol}, volume = {17}, year = {2021}, month = {2021 Jul}, pages = {e1009126}, abstract = {

COVID-19 testing across India uses a mix of two types of tests. Rapid Antigen Tests (RATs) are relatively inexpensive point-of-care lateral-flow-assay tests, but they are also less sensitive. The reverse-transcriptase polymerase-chain-reaction (RT-PCR) test has close to 100\% sensitivity and specificity in a laboratory setting, but delays in returning results, as well as increased costs relative to RATs, may vitiate this advantage. India-wide, about 49\% of COVID-19 tests are RATs, but some Indian states, including the large states of Uttar Pradesh (pop. 227.9 million) and Bihar (pop. 121.3 million) use a much higher proportion of such tests. Here we show, using simulations based on epidemiological network models, that the judicious use of RATs can yield epidemiological outcomes comparable to those obtained through RT-PCR-based testing and isolation of positives, provided a few conditions are met. These are (a) that RAT test sensitivity is not too low, (b) that a reasonably large fraction of the population, of order 0.5\% per day, can be tested, (c) that those testing positive are isolated for a sufficient duration, and that (d) testing is accompanied by other non-pharmaceutical interventions for increased effectiveness. We assess optimal testing regimes, taking into account test sensitivity and specificity, background seroprevalence and current test pricing. We find, surprisingly, that even 100\% RAT test regimes should be acceptable, from both an epidemiological as well as a economic standpoint, provided the conditions outlined above are met.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1009126}, author = {Cherian, Philip and Krishna, Sandeep and Menon, Gautam I} } @inbook {82598, title = {Patterned Optogenetic Stimulation Using a DMD Projector.}, booktitle = {Channelrhodopsin}, volume = {2191}, number = {Methods Mol Biol}, year = {2021}, month = {2021}, pages = {173-188}, publisher = {Humana-Springer}, organization = {Humana-Springer}, abstract = {

Optical manipulation is a powerful way to control neural activity in vitro and in vivo with millisecond precision. Patterning of light provides the remarkable ability to simultaneously target spatially segregated neurons from a population. Commercially available projectors provide one of the simplest and most economical ways of achieving spatial light modulation at millisecond timescales. Here, we describe the protocol for constructing a projector-based spatio-temporal light patterning system integrated with a microscope on a typical electrophysiology rig. The set-up is well suited for applications requiring rapid, distinct, and combinatorial inputs, akin to brain activity. This equipment involved is fairly economical (\<$5000 including all optical and mechanical components), and the set-up is easy to assemble and program.

}, isbn = {978-1-0716-0829-6}, doi = {10.1007/978-1-0716-0830-2_11}, author = {Bhatia, Aanchal and Moza, Sahil and Bhalla, Upinder S} } @article {93655, title = {Performance of larval parasitoid, Bracon brevicornis on two Spodoptera hosts: implication in bio-control of Spodoptera frugiperda}, journal = {JOURNAL OF PEST SCIENCE}, year = {2021}, month = {05/2021}, abstract = {

Successful pest management using parasitoids requires careful evaluation of host-parasitoid interactions. Here, we report the performance of larval ecto-parasitoid wasp, Bracon brevicornis (Wesmael) on important agricultural pests, Spodoptera litura (Fabricius) and S. frugiperda (J.E. Smith). Biology of B. brevicornis was studied on different host instars under laboratory and cage setup. In no-choice assay, the parasitoid development was highest on fifth-instar S. litura larvae as the wasp laid similar to 253 eggs with 62\% hatching, 76\% pupae formation and 78\% adult emergence. Similarly, these parameters were highest on fifth instar S. frugiperda larvae (293 eggs, 57\% hatching, 80\% pupae formation, 70\% adult emergence). In two-choice assay, B. brevicornis preferred fourth or fifth over third instar larvae of both hosts. Successful parasitism depends on host paralysis and suppression of host immunity. B. brevicornis interaction downregulated cellular immunity of both hosts as shown by reduced hemocyte viability and spreading. The percent parasitism rate of B. brevicornis was unaltered in the presence of host plant, Zea mays in cage study. 76 and 84\% parasitism was observed on fifth-instar larvae of S. litura and S. frugiperda, respectively. We evaluated the performance of B. brevicornis as a biocontrol agent on S. frugiperda in maize field. Our results show 54\% average reduction in infestation after release of B. brevicornis. Taken together, we report the performance of B. brevicornis on important insect pests for the first time in laboratory and field conditions. Our findings indicate that B. brevicornis is a promising candidate for integrated pest management.

}, doi = {10.1007/s10340-021-01385-0}, author = {Ghosh, Enakshi and Varshney, Richa and Venkatesan, Radhika} } @article {89985, title = {Phenotypic Clumping Decreases With Flock Richness in Mixed-Species Bird Flocks}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, year = {2021}, month = {01/2021}, abstract = {

Animals that live in groups may experience positive interactions such as cooperative behavior or negative interactions such as competition from group members depending on group size and similarity between individuals. The effect of group size and phenotypic and ecological similarity on group assembly has not been well-studied. Mixed-species flocks are important subsets of bird communities worldwide. We examined associations within these in relation to flock size, to understand rules of flock assembly, in the Western Ghats of India. We examined the relationship between phenotypic clumping and flock richness using four variables-body size, foraging behavior, foraging height and taxonomic relatedness. Using a null model approach, we found that small flocks were more phenotypically clumped for body size than expected by chance; however, phenotypic clumping decreased as flocks increased in size and approached expected phenotypic variation in large flocks. This pattern was not as clear for foraging height and foraging behavior. We then examined a dataset of 55 flock matrices from 24 sites across the world. We found that sites with smaller flocks had higher values of phenotypic clumping for body size and sites with larger flocks were less phenotypically clumped. This relationship was weakly negative for foraging behavior and not statistically significant for taxonomic relatedness. Unlike most single-species groups, participants in mixed-species flocks appear to be able to separate on different axes of trait similarity. They can gain benefits from similarity on one axis while mitigating competition by dissimilarity on others. Consistent with our results, we speculate that flock assembly was deterministic up to a certain point with participants being similar in body size, but larger flocks tended to approach random phenotypic assemblages of species.

}, doi = { 10.3389/fevo.2020.537816}, author = {Bangal, Priti and Sridhar, Hari and Shanker, Kartik} } @article {89986, title = {The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 Feb 18}, pages = {4178}, abstract = {

The X family is one of the eight families of DNA polymerases (dPols) and members of this family are known to participate in the later stages of Base Excision Repair. Many prokaryotic members of this family possess a Polymerase and Histidinol Phosphatase (PHP) domain at their C-termini. The PHP domain has been shown to possess 3{\textquoteright}-5{\textquoteright} exonuclease activity and may represent the proofreading function in these dPols. PolX from Staphylococcus aureus also possesses the PHP domain at the C-terminus, and we show that this domain has an intrinsic Mn dependent 3{\textquoteright}-5{\textquoteright} exonuclease capable of removing misincorporated dNMPs from the primer. The misincorporation of oxidized nucleotides such as 8oxodGTP and rNTPs are known to be pro-mutagenic and can lead to genomic instability. Here, we show that the PHP domain aids DNA replication by the removal of misincorporated oxidized nucleotides and rNMPs. Overall, our study shows that the proofreading activity of the PHP domain plays a critical role in maintaining genomic integrity and stability. The exonuclease activity of this enzyme can, therefore, be the target of therapeutic intervention to combat infection by methicillin-resistant-Staphylococcus-aureus.

}, issn = {2045-2322}, doi = {10.1038/s41598-021-83498-1}, author = {Nagpal, Shilpi and Nair, Deepak T} } @article {78098, title = {Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life.}, journal = {Syst Biol}, volume = {70}, year = {2021}, month = {2020 May 02}, pages = {49-66}, abstract = {

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94\% of the families and 44\% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree-species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets.

}, issn = {1076-836X}, doi = {10.1093/sysbio/syaa034}, author = {Hime, Paul M and Lemmon, Alan R and Lemmon, Emily C Moriarty and Prendini, Elizabeth and Brown, Jeremy M and Thomson, Robert C and Kratovil, Justin D and Noonan, Brice P and Pyron, R Alexander and Peloso, Pedro L V and Kortyna, Michelle L and Keogh, J Scott and Donnellan, Stephen C and Mueller, Rachel Lockridge and Raxworthy, Christopher J and Kunte, Krushnamegh and Ron, Santiago R and Das, Sandeep and Gaitonde, Nikhil and Green, David M and Labisko, Jim and Che, Jing and Weisrock, David W} } @article {95003, title = {Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.}, journal = {Proc Natl Acad Sci U S A}, volume = {118}, year = {2021}, month = {2021 Jun 29}, abstract = {

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.

}, issn = {1091-6490}, doi = {10.1073/pnas.2026786118}, author = {Yang, Xingbo and Heinemann, Matthias and Howard, Jonathon and Huber, Greg and Iyer-Biswas, Srividya and Le Treut, Guillaume and Lynch, Michael and Montooth, Kristi L and Needleman, Daniel J and Pigolotti, Simone and Rodenfels, Jonathan and Ronceray, Pierre and Shankar, Sadasivan and Tavassoly, Iman and Thutupalli, Shashi and Titov, Denis V and Wang, Jin and Foster, Peter J} } @article {95004, title = {Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.}, journal = {Front Mol Neurosci}, volume = {14}, year = {2021}, month = {2021}, pages = {658435}, abstract = {

SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists in the expression of channel isoforms in distinct brain regions and various subcellular compartments, which contributes to an equally diverse set of specific neuronal functions. The current review emphasizes the collective behavior of the three classes of mAHP channels and discusses how these channels function together although they play specialized roles. We discuss the biophysical properties of these channels, signaling pathways that influence the activity of the three mAHP channels, various chemical modulators that alter channel activity and their therapeutic potential in treating various neurological anomalies. Additionally, we discuss the role of mAHP channels in the pathophysiology of various neurological diseases and how their modulation can alleviate some of the symptoms.

}, issn = {1662-5099}, doi = {10.3389/fnmol.2021.658435}, author = {Dwivedi, Deepanjali and Bhalla, Upinder S} } @article {91469, title = {Plk4 triggers autonomous de novo centriole biogenesis and maturation.}, journal = {J Cell Biol}, volume = {220}, year = {2021}, month = {2021 May 03}, abstract = {

Centrioles form centrosomes and cilia. In most proliferating cells, centrioles assemble through canonical duplication, which is spatially, temporally, and numerically regulated by the cell cycle and the presence of mature centrioles. However, in certain cell types, centrioles assemble de novo, yet by poorly understood mechanisms. Herein, we established a controlled system to investigate de novo centriole biogenesis, using Drosophila melanogaster egg explants overexpressing Polo-like kinase 4 (Plk4), a trigger for centriole biogenesis. We show that at a high Plk4 concentration, centrioles form de novo, mature, and duplicate, independently of cell cycle progression and of the presence of other centrioles. Plk4 concentration determines the temporal onset of centriole assembly. Moreover, our results suggest that distinct biochemical kinetics regulate de novo and canonical biogenesis. Finally, we investigated which other factors modulate de novo centriole assembly and found that proteins of the pericentriolar material (PCM), and in particular γ-tubulin, promote biogenesis, likely by locally concentrating critical components.

}, issn = {1540-8140}, doi = {10.1083/jcb.202008090}, author = {Nabais, Catarina and Pessoa, Delphine and de-Carvalho, Jorge and van Zanten, Thomas and Duarte, Paulo and Mayor, Satyajit and Carneiro, Jorge and Telley, Ivo A and Bettencourt-Dias, M{\'o}nica} } @article {93671, title = {Pluripotent Stem Cell Derived Neurons as In Vitro Models for Studying Autosomal Recessive Parkinson{\textquoteright}s Disease (ARPD): PLA2G6 and Other Gene Loci.}, journal = {Adv Exp Med Biol}, year = {2021}, month = {2021 May 15}, abstract = {

Parkinson{\textquoteright}s disease (PD) is a neurodegenerative motor disorder which is largely sporadic; however, some familial forms have been identified. Genetic PD can be inherited by autosomal, dominant or recessive mutations. While the dominant mutations mirror the prototype of PD with adult-onset and L-dopa-responsive cases, autosomal recessive PD (ARPD) exhibit atypical phenotypes with additional clinical manifestations. Young-onset PD is also very common with mutations in recessive gene loci. The main genes associated with ARPD are Parkin, PINK1, DJ-1, ATP13A2, FBXO7 and PLA2G6. Calcium dyshomeostasis is a mainstay in all types of PD, be it genetic or sporadic. Intriguingly, calcium imbalances manifesting as altered Store-Operated Calcium Entry (SOCE) is suggested in PLA2G6-linked PARK 14 PD. The common pathways underlying ARPD pathology, including mitochondrial abnormalities and autophagic dysfunction, can be investigated ex vivo using induced pluripotent stem cell (iPSC) technology and are discussed here. PD pathophysiology is not faithfully replicated by animal models, and, therefore, nigral dopaminergic neurons generated from iPSC serve as improved human cellular models. With no cure to date and treatments aiming at symptomatic relief, these in vitro models derived through midbrain floor-plate induction provide a platform to understand the molecular and biochemical pathways underlying PD etiology in a patient-specific manner.

}, issn = {0065-2598}, doi = {10.1007/5584_2021_643}, author = {Gopurappilly, Renjitha} } @article {92431, title = {Purkinje neurons with loss of STIM1 exhibit age-dependent changes in gene expression and synaptic components}, journal = {J Neurosci.}, year = {2021}, month = {03/2021}, abstract = {

The Stromal interaction molecule 1 (STIM1), is an ER-Ca2+ sensor and an essential component of ER-Ca2+ store operated Ca2+ entry (SOCE). Loss of STIM1 affects metabotropic Glutamate Receptor 1 (mGluR1) mediated synaptic transmission, neuronal Ca2+ homeostasis and intrinsic plasticity in Purkinje Neurons (PNs). Long-term changes of intracellular Ca2+ signaling in PNs lead to neurodegenerative conditions, as evident in individuals with mutations of the ER-Ca2+ channel, the Inositol 1,4,5-triphosphate receptor (IP3R). Here, we asked if changes in such intrinsic neuronal properties, due to loss of STIM1, have an age-dependent impact on PNs. Consequently, we analyzed mRNA expression profiles and cerebellar morphology in PN specific STIM1 knockout mice (STIM1PKO ) of both sexes across ages. Our study identified a requirement for STIM1 mediated Ca2+ signaling in maintaining the expression of genes belonging to key biological networks of synaptic function and neurite development amongst others. Gene expression changes correlated with altered patterns of dendritic morphology and greater innervation of PN dendrites by climbing fibers, in ageing STIM1PKO mice. Together, our data identify STIM1 as an important regulator of Ca2+ homeostasis and neuronal excitability in turn required for maintaining the optimal transcriptional profile of PNs with age. Our findings are significant in the context of understanding how dysregulated calcium signals impact cellular mechanisms in multiple neurodegenerative disorders.Significance StatementIn Purkinje neurons (PNs) the Stromal interaction molecule 1 (STIM1) is required for mGluR1-dependent synaptic transmission, refilling of ER Ca2+ stores, regulation of spike frequency and cerebellar memory consolidation. Here, we provide evidence for a novel role of STIM1 in maintaining the gene expression profile and optimal synaptic connectivity of PNs. Expression of genes related to neurite development and synaptic organization networks are altered in PNs with persistent loss of STIM1. In agreement with these findings the dendritic morphology of PNs and climbing fiber innervations on PNs also undergo significant changes with age. These findings identify a new role for dysregulated intracellular calcium signaling in neurodegenerative disorders and provide novel therapeutic insights.

}, doi = {10.1523/JNEUROSCI.2401-20.2021}, author = {Dhanya, SK and Hasan, Gaiti} } @article {102046, title = {Rational Design of Protein-Specific Folding Modifiers.}, journal = {J Am Chem Soc}, year = {2021}, month = {2021 Nov 01}, abstract = {

Protein-folding can go wrong and , with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein. Using stopped-flow kinetics, NMR spectroscopy, F{\"o}rster resonance energy transfer, single-molecule force measurements, and molecular dynamics simulations, we demonstrate that a xenonucleus can make the refolding of ubiquitin faster by 33 {\textpm} 5\%, while variants of the same peptide have little or no effect. Our approach provides a novel method for constructing specific, genetically encodable folding catalysts for suitable proteins that have a well-defined contiguous folding nucleus.

}, issn = {1520-5126}, doi = {10.1021/jacs.1c09611}, author = {Das, Anirban and Yadav, Anju and Gupta, Mona and R, Purushotham and Terse, Vishram L and Vishvakarma, Vicky and Singh, Sameer and Nandi, Tathagata and Banerjee, Arkadeep and Mandal, Kalyaneswar and Gosavi, Shachi and Das, Ranabir and Ainavarapu, Sri Rama Koti and Maiti, Sudipta} } @article {103405, title = {Recapitulating whole genome based population genetic structure for Indian wild tigers through an ancestry informative marker panel}, journal = { Heredity (Edinb)}, year = {2021}, month = {12/2021}, abstract = {

Identification of genetic structure within wildlife populations have implications in their conservation and management. Accurately inferring population genetic structure requires whole-genome data across the geographical range of the species, which can be resource-intensive. A cheaper strategy is to employ a subset of markers that can efficiently recapitulate the population genetic structure inferred by the whole genome data. Such ancestry informative markers (AIMs), have rarely been developed for endangered species such as tigers utilizing single nucleotide polymorphisms (SNPs). Here, we first identify the population structure of the Indian tiger using whole-genome sequences and then develop an AIMs panel with a minimum number of SNPs that can recapitulate this structure. We identified four population clusters of Indian tigers with North-East, North-West, and South Indian tigers forming three separate groups, and Terai and Central Indian tigers forming a single cluster. To evaluate the robustness of our AIMs, we applied it to a separate dataset of tigers from across India. Out of 92 SNPs present in our AIMs panel, 49 were present in the new dataset. These 49 SNPs were sufficient to recapitulate the population genetic structure obtained from the whole genome data. To the best of our knowledge, this is the first-ever SNP-based AIMs panel for big cats, which can be used as a cost-effective alternative to whole-genome sequencing for detecting the biogeographical origin of Indian tigers. Our study can be used as a guideline for developing an AIMs panel for the management of other endangered species where obtaining whole genome sequences are difficult.

}, doi = {10.1038/s41437-021-00477-y}, author = {Khan, Anubhab and Krishna, S.M. and Ramakrishnan, Uma and Das, Ranajit} } @article {89659, title = {Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection.}, journal = {Mol Biol Evol}, year = {2021}, month = {2021 Feb 16}, abstract = {

Species conservation can be improved by knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, their evolutionary history and genomic variation remains poorly known, especially for Indian tigers. With 70\% of the worlds wild tigers living in India, such knowledge is critical. We re-sequenced 65 individual tiger genomes representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding or founding events, possibly due to small and fragmented protected areas. We suggest the impacts of ongoing connectivity loss on inbreeding and persistence of Indian tigers be closely monitored. Surprisingly, demographic models suggest recent divergence (within the last 20,000 years) between subspecies, and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection related to metabolic adaptation to cold, while Sumatran tigers show evidence of weak selection for genes involved in body size regulation. We recommend detailed investigation of local adaptation in Amur and Sumatran tigers prior to initiating genetic rescue.

}, issn = {1537-1719}, doi = {10.1093/molbev/msab032}, author = {Armstrong, Ellie E and Khan, Anubhab and Taylor, Ryan W and Gouy, Alexandre and Greenbaum, Gili and Thi{\'e}ry, Alexandre and Kang, Jonathan T L and Redondo, Sergio A and Prost, Stefan and Barsh, Gregory and Kaelin, Christopher and Phalke, Sameer and Chugani, Anup and Gilbert, Martin and Miquelle, Dale and Zachariah, Arun and Borthakur, Udayan and Reddy, Anuradha and Louis, Edward and Ryder, Oliver A and Jhala, Y V and Petrov, Dmitri and Excoffier, Laurent and Hadly, Elizabeth and Ramakrishnan, Uma} } @article {87277, title = {Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms}, journal = {Chem Senses}, volume = {46}, year = {2021}, month = {12/2020}, abstract = {

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean{\textpm}SD, C19+: -82.5{\textpm}27.2 points; C19-: -59.8{\textpm}37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50\% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings <=2 indicate high odds of symptomatic COVID-19 (4\<OR\<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

}, doi = {10.1093/chemse/bjaa081}, author = {Gerkin, RC and Ohla, K and Veldhuizen, MG and Joseph, PV and Kelly, CE and Bakke, AJ and Steele, KE and Farruggia, MC and Pellegrino, R and Pepino, MY and Bouysset, C and Soler, GM and Pereda-Loth, V and Dibattista, M and Cooper, KW and Croijmans, I and Di Pizio, A and Ozdener, MH and Fjaeldstad, AW and Lin, C and Sandell, MA and Singh, PB and Brindha, VE and Olsson, SB and Saraiva, LR and Ahuja, G and Alwashahi, MK and Bhutani, S and D{\textquoteright}Errico, A and Fornazieri, MA and Golebiowski, J and Hwang, LD and {\"O}zt{\"u}rk, L and Roura, E and Spinelli, S and Whitcroft, KL and Faraji, F and Fischmeister, FP and Heinbockel, T and Hsieh, JW and Huart, C and Konstantinidis, I and Menini, A and Morini, G and Olofsson, JK and Philpott, CM and Pierron, D and Shields, VDC and Voznessenskaya, VV and Albayay, J and Altundag, A and Bensafi, M and Bock, MA and Calcinoni, O and Fredborg, W and Laudamiel, C and Lim, J and Lundstr{\"o}m, JN and Macchi, A and Meyer, P and Moein, ST and Santamar{\'\i}a, E and Sengupta, D and Dominguez, PR and Yanik, H and Hummel, T and Hayes, JE and Reed, DR and Niv, MY and Munger, SD and Parma, V and GCCR Group} } @article {96750, title = {Reciprocal regulation of spontaneous synaptic vesicle fusion by Fragile X mental retardation protein and group I metabotropic glutamate receptors.}, journal = {J Neurochem}, year = {2021}, month = {2021 Jul 29}, abstract = {

Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a range of aberrations in synaptic signaling pathways and plasticity associated with group I metabotropic glutamate (mGlu) receptors. These studies, however, have mostly focused on the postsynaptic functions of FMRP and mGlu receptor activation, and relatively little is known about their presynaptic effects. Neurotransmitter release is mediated via multiple forms of synaptic vesicle (SV) fusion, each of which contribute to specific neuronal functions. The impacts of mGlu receptor activation and loss of FMRP on these SV fusion events remains unexplored. Here we combined electrophysiological and fluorescence imaging analyses on primary hippocampal cultures prepared from a Fmr1 knockout (KO) rat model. Compared to wild-type (WT) hippocampal neurons, KO neurons displayed an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), as well as spontaneous SV fusion events. Pharmacological activation of mGlu receptors in WT neurons caused a similar increase in spontaneous SV fusion and sEPSC frequency. Notably, this increase in SV fusion was not observed when spontaneous activity was blocked using the sodium channel antagonist tetrodotoxin. Importantly, the effect of mGlu receptor activation on spontaneous SV fusion was occluded in Fmr1 KO neurons. Together, our results reveal that FMRP represses spontaneous presynaptic SV fusion, whereas mGlu receptor activation increases this event. This reciprocal control appears to be mediated via their regulation of intrinsic neuronal excitability.

}, issn = {1471-4159}, doi = {10.1111/jnc.15484}, author = {Subrahmanyam, Rohini and Dwivedi, Deepanjali and Rashid, Zubin and Bonnycastle, Katherine and Cousin, Michael A and Chattarji, Sumantra} } @article {85179, title = {Redefining genetic essentiality in Mycobacterium tuberculosis.}, journal = {Gene}, volume = {765}, year = {2021}, month = {2021 Jan 10}, pages = {145091}, abstract = {

Sequencing transposon mutant libraries have been pivotal in annotating essential and non-essential genes in bacteria. This is particularly very helpful in the case of Mycobacterium tuberculosis with a large part of its genome without known function. It is not known whether there are any variations in the essentiality states as a function of optimal growth in the absence of any selection pressure. We here grow a high-density mutant library of M. tuberculosis through serial cultures and monitor the temporal fluctuations in insertion frequencies across all TA dinucleotides in the genome. Genes that cause morphological and physiological heterogeneity or enable metabolic bypass were found to gradually lose insertions, while genes comprising the toxin-antitoxin systems were found to get enriched with insertions during growth in nutrient replete conditions. High levels of fluctuations were observed in genes involved in cell wall and cell processes, intermediary metabolism, and genes involved in virulence, suggesting new modes of adaptation undertaken by the mutants. We also report the essentiality status of several newly annotated genetic features.

}, issn = {1879-0038}, doi = {10.1016/j.gene.2020.145091}, author = {Patil, Saniya and Palande, Aseem and Lodhiya, Tejan and Pandit, Awadhesh and Mukherjee, Raju} } @article {91137, title = {Repeated victorious and defeat experiences induce similar apical dendritic spine remodeling in CA1 hippocampus of rats.}, journal = {Behav Brain Res}, volume = {406}, year = {2021}, month = {2021 Mar 13}, pages = {113243}, abstract = {

In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (\>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study. Both winners and losers were socially housed during the experiments; winners with females to stimulate territorial behavior, and losers with two other losing male rats. Twenty-four hours after the last social encounter, brains from experienced residential winners and repeatedly defeated intruder rats were collected and neuronal morphology in selected brain regions was studied via Golgi-Cox staining. Results indicate that spine density in the apical dendrites of the hippocampal CA1 reduced similarly in both winners and losers. In addition, winners showed increased spine densities at the proximal segments (20-30 μm) of the basolateral amygdala neurons and losers tended to show a decreased spine density at the more proximal segments of the infralimbic region of prefrontal cortex neurons. No effect of winning and losing was observed in the medial amygdala. The atrophic effect of repeated defeats in hippocampal and prefrontal regions was anticipated despite the fact that social housing of the repeatedly losing intruder males may have played a protective role. The reduction of hippocampal spine density in the winners seems surprising but supports previous findings in hierarchical dominant males in rat colonies. The dominants showed even greater shrinkage of the apical dendritic arbors of hippocampal CA3 pyramidal neurons compared to the stressed subordinates.

}, issn = {1872-7549}, doi = {10.1016/j.bbr.2021.113243}, author = {Patel, Deepika and Anilkumar, Shobha and Chattarji, Sumantra and de Boer, Sietse F and Buwalda, Bauke} } @article {91471, title = {Resolving Site-Specific Heterogeneity of the Unfolded State under Folding Conditions.}, journal = {J Phys Chem Lett}, year = {2021}, month = {2021 Mar 25}, pages = {3295-3302}, abstract = {

Understanding the properties of the unfolded state under folding conditions is of fundamental importance for gaining mechanistic insight into folding as well as misfolding reactions. Toward achieving this objective, the folding reaction of a small protein, monellin, has been resolved structurally and temporally, with the use of the multisite time-resolved FRET methodology. The present study establishes that the initial polypeptide chain collapse is not only heterogeneous but also structurally asymmetric and nonuniform. The population-averaged size for the segments spanning parts of the β-sheet decreases much more than that for the α-helix. Multisite measurements enabled specific and nonspecific components of the initial chain collapse to be discerned. The expanded and compact intermediate subensembles have the properties of a nonspecifically collapsed (hence, random-coil-like) and specifically collapsed (hence, globular) polymer, respectively. During subsequent folding, both the subensembles underwent contraction to varying extents at the four monitored segments, which was close to gradual in nature. The expanded intermediate subensemble exhibited an additional very slow contraction, suggestive of the presence of non-native interactions that result in a higher effective viscosity slowing down intrachain motions under folding conditions.

}, issn = {1948-7185}, doi = {10.1021/acs.jpclett.1c00098}, author = {Bhatia, Sandhya and Krishnamoorthy, Guruswamy and Udgaonkar, Jayant B} } @article {96679, title = {Restoring tropical forest{\textendash}grassland mosaics invaded by woody exotics}, journal = {Restor Ecol }, year = {2021}, month = {07/2021}, abstract = {

Although important for biological conservation and provisioning of several ecosystem services, tropical forest{\textendash}grassland mosaics face several threats, one of which is woody invasion in grasslands of these mosaics{\textemdash}an issue proving to be challenging to solve. We present a framework to guide grassland restoration in these mosaics that takes into account their unique ecology, outlines a general chronological sequence of restoration activities, and helps identify research priorities to guide restoration efforts. Specifically, we outline approaches to (1) increase the cost-effectiveness of restoration programs (e.g. selecting restoration targets and priority sites); (2) restore edaphic processes impacted by woody invasion; (3) maximize the establishment of native grass and forb species, and (4) maintain restored communities in the long-term by minimizing re-invasions. We apply this framework to montane southern Indian forest-grassland mosaics (locally called shola-grassland mosaics) invaded by nitrogen-fixing woody exotics to identify research priorities that can act as {\textquotedblleft}game-changers{\textquotedblright} in the restoration of these ecosystems. These include (1) identifying invaded areas where passive restoration can be effective, (2) understanding the role of endogenous disturbances, particularly fire, in the spread and management of invasive species and the prevention of re-invasion, and (3) assessing the role of large-scale seed farming and emerging seed technologies for the use of seeds to effectively re-introduce native grassland species. Restoration frameworks that take into account unique ecologies are needed to make the most of the UN Decade on Ecosystem Restoration, and we present such a framework for forest-grassland mosaics{\textemdash}an important ecosystem that is generally neglected.

}, doi = {10.1111/rec.13491}, author = {Raghurama, Manaswi and Sankaran, Mahesh} } @article {91468, title = {A reversal in sensory processing accompanies ongoing ecological divergence and speciation in .}, journal = {Proc Biol Sci}, volume = {288}, year = {2021}, month = {2021 Mar 31}, pages = {20210192}, abstract = {

Changes in behaviour often drive rapid adaptive evolution and speciation. However, the mechanistic basis for behavioural shifts is largely unknown. The tephritid fruit fly is an example of ecological specialization and speciation in action via a recent host plant shift from hawthorn to apple. These flies primarily use specific odours to locate fruit, and because they mate only on or near host fruit, changes in odour preference for apples versus hawthorns translate directly to prezygotic reproductive isolation, initiating speciation. Using a variety of techniques, we found a reversal between apple and hawthorn flies in the sensory processing of key odours associated with host fruit preference at the first olfactory synapse, linking changes in the antennal lobe of the brain with ongoing ecological divergence. Indeed, changes to specific neural pathways of any sensory modality may be a broad mechanism for changes in animal behaviour, catalysing the genesis of new biodiversity.

}, issn = {1471-2954}, doi = {10.1098/rspb.2021.0192}, author = {Tait, Cheyenne and Kharva, Hinal and Schubert, Marco and Kritsch, Daniel and Sombke, Andy and Rybak, J{\"u}rgen and Feder, Jeffrey L and Olsson, Shannon B} } @article {102989, title = {A review of the Drepanosticta carmichaeli-group, with the description of D. wildermuthi sp. nov. from the Central Highlands of Vietnam (Odonata: Zygoptera: Platystictidae).}, journal = {Zootaxa}, volume = {5067}, year = {2021}, month = {2021 Nov 10}, pages = {187-210}, abstract = {

A modified and expanded definition of the Drepanosticta carmichaeli-group is given. This includes the species: D. annandalei Fraser, 1924, D. brownelli Tinkham, 1938, D. carmichaeli (Laidlaw, 1915), D. emtrai Dow, Kompier Phan, 2018, D. hongkongensis Wilson, 1997, D. jurzitzai Hmlinen, 1999, D. sumatrana Sasamoto Karube, 2007, D. tenella Lieftinck, 1935, D. vietnamica Asahina, 1997 and D. wildermuthi sp. nov.). The species of the group are reviewed and in most cases illustrated, diagnostic notes are given wherever possible. Drepanosticta polychromatica Fraser, 1931 is considered to be a junior synonym of D. carmichaeli and variation in D. carmichaeli is discussed. Drepanosticta wildermuthi sp. nov. from the Central Highlands of Vietnam (holotype male from Bao Loc district, Lam Dong Province) is described. The female of D. jurzitzai Hmlinen, 1999 is described for the first time. A key to the males of the Drepanosticta carmichaeli-group is provided.

}, keywords = {Animals, Female, Male, Odonata, Vietnam}, issn = {1175-5334}, doi = {10.11646/zootaxa.5067.2.2}, author = {Phan, Quoc Toan and Yokoi, Naoto and Makbun, Noppadon and Joshi, Shantanu and Subramanian, K A and Ngo, Quoc Phu and Dow, Rory A} } @article {82950, title = {Rice-specific Argonaute 17 controls reproductive growth and yield-associated phenotypes.}, journal = {Plant Mol Biol}, volume = {105}, year = {2021}, month = {2020 Sep 22}, pages = {99-114}, abstract = {

KEY MESSAGE: This manuscript describes the functions of an Argonaute protein named AGO17 in rice. AGO17 is required for the development of rice reproductive tissues. Argonaute (AGO) proteins are a well-conserved multigene family of regulators mediating gene silencing across eukaryotes. Monocot plants have additional members of AGO, the functions of which are poorly understood. Among the non-dicot AGO1 clade members in monocots, AGO17 expresses highly in reproductive tissues. Here we show that overexpression of Oryza sativa indica AGO17 in rice resulted in robust growth and increased yield, whereas its silencing resulted in reduced panicle length, less fertility, and poor growth. Small (s)RNA transcriptome analysis revealed misregulation of several miRNAs and other categories of sRNAs in silenced and overexpression lines, in agreement with its likely competition with other AGO1 clade members. Targets of differentially expressed miRNAs included previously unreported target RNAs coding for proteins involved in development, phase transition, and transport. Our results indicate a distinctive role for OsAGO17 in rice reproductive development that could be harnessed to improve yield.

}, issn = {1573-5028}, doi = {10.1007/s11103-020-01071-2}, author = {Pachamuthu, Kannan and Swetha, Chenna and Basu, Debjani and Das, Soumita and Singh, Indira and Sundar, Vivek Hari and Sujith, T N and Shivaprasad, Padubidri V} } @article {95781, title = {RNA diversification by a self-reproducing ribozyme revealed by deep sequencing and kinetic modelling.}, journal = {Chem Commun (Camb)}, year = {2021}, month = {2021 Jul 08}, abstract = {

We demonstrate that a recombinase ribozyme achieves multiple functions in the same reaction network: self-reproduction, iterative elongation and circularization of other RNAs, leading to synthesis of diverse products predicted by a kinetic model. This shows that key mechanisms can be integrated and controlled toward Darwinian evolution in RNA reaction networks.

}, issn = {1364-548X}, doi = {10.1039/d1cc02290c}, author = {Jeancolas, Cyrille and Matsubara, Yoshiya J and Vybornyi, Mykhailo and Lambert, Camille N and Blokhuis, Alex and Alline, Thomas and Griffiths, Andrew D and Ameta, Sandeep and Krishna, Sandeep and Nghe, Philippe} } @article {99110, title = {The roles of serotonin in cell adhesion and migration, and cytoskeletal remodeling.}, journal = {Cell Adh Migr}, volume = {15}, year = {2021}, month = {2021 12}, pages = {261-271}, abstract = {

Serotonin is well known\ as a neurotransmitter. Its roles in neuronal processes such as learning, memory or cognition are well established, and also in\ disorders\ such as\ depression, schizophrenia, bipolar disorder,\ and dementia. However,\ its\ effects on adhesion and cytoskeletal remodelling which are strongly affected by 5-HT receptors,\ are\ not\ as\ well studied\ with some exceptions\ for e.g.\ platelet aggregation.\ Neuronal function is strongly dependent on cell-cell\ contacts\ and\ adhesion-related processes.\ Therefore the role\ played by\ serotonin\ in psychiatric illness,\ as well as\ in the\ positive and negative effects of neuropsychiatric drugs\ through\ cell-related\ adhesion\ can be of great significance. In this review, we explore\ the role of serotonin in some of these\ aspects based on recent findings.

}, issn = {1933-6926}, doi = {10.1080/19336918.2021.1963574}, author = {John Jayakumar, Joe Anand Kumar and Panicker, Mitradas M} } @article {102565, title = {A salience hypothesis of stress in PTSD.}, journal = {Eur J Neurosci}, year = {2021}, month = {2021 Nov 11}, abstract = {

Attention to key features of contexts and things is a necessary tool for all organisms. Detecting these salient features of cues, or simply, salience, can also be affected by exposure to traumatic stress, as has been widely reported in individuals suffering from Post-Traumatic Stress Disorder (PTSD). Interestingly, similar observations have been robustly replicated across many animal models of stress as well. By using evidence from such rodent stress paradigms, in the present review we explore PTSD through the lens of salience processing. In this context, we propose that interaction between the neurotrophin BDNF and glucocorticoid determines the long lasting cellular and behavioural consequences of stress salience. We also describe the dual effect of glucocorticoid therapy in the amelioration of PTSD symptoms. Finally, by integrating in vivo observations at multiple scales of plasticity, we propose a unifying hypothesis that pivots on a crucial role of glucocorticoid signalling in dynamically orchestrating stress salience.

}, issn = {1460-9568}, doi = {10.1111/ejn.15526}, author = {Chakraborty, Prabahan and Chattarji, Sumantra and Jeanneteau, Freddy} } @article {96165, title = {Search Behavior of Individual Foragers Involves Neurotransmitter Systems Characteristic for Social Scouting}, journal = {Front. Insect Sci}, year = {2021}, month = {06/2021}, abstract = {

In honey bees search behavior occurs as social and solitary behavior. In the context of foraging, searching for food sources is performed by behavioral specialized foragers, the scouts. When the scouts have found a new food source, they recruit other foragers (recruits). These recruits never search for a new food source on their own. However, when the food source is experimentally removed, they start searching for that food source. Our study provides a detailed description of this solitary search behavior and the variation of this behavior among individual foragers. Furthermore, mass spectrometric measurement showed that the initiation and performance of this solitary search behavior is associated with changes in glutamate, GABA, histamine, aspartate, and the catecholaminergic system in the optic lobes and central brain area. These findings strikingly correspond with the results of an earlier study that showed that scouts and recruits differ in the expression of glutamate and GABA receptors. Together, the results of both studies provide first clear support for the hypothesis that behavioral specialization in honey bees is based on adjusting modulatory systems involved in solitary behavior to increase the probability or frequency of that behavior.

}, doi = {10.3389/finsc.2021.664978}, author = {Chatterjee, Arumoy and Bais, Deepika and Brockmann, Axel and Ramesh, Divya} } @article {95904, title = {Seasonal drought regulates species distributions and assembly of tree communities across a tropical wet forest region}, journal = {GLOBAL ECOLOGY AND BIOGEOGRAPHY}, year = {2021}, month = {07/2021}, abstract = {

Aim How seasonal drought influences tree species distributions might shape future vegetation composition with impending changes to rainfall patterns. Theory suggests that across a seasonal drought gradient, dry-tolerant species might have wider distributions than species sensitive to seasonal drought, which will be restricted to less seasonal conditions. As wet-associated species drop out with increasing seasonality, the community will contain mainly dry-tolerant species. Time period Present. Location Western Ghats Biodiversity Hotspot in peninsular India. Major taxa studied Woody angiosperms. Methods Across a 1,200 km seasonal drought gradient, we modelled occurrences of 183 species using Gaussian logistic regression in a hierarchical Bayesian framework. We used the first-order model coefficients to attribute the association of species to seasonality (dry/wet) and second-order coefficients to assess modal responses. For 92 species, we checked for an interaction between dry/wet association and two traits: wood density and specific leaf area (SLA). Finally, we assessed the consequences of the seasonality associations of species for regional community assembly. Results Of 183 species, 38\% were significantly wet associated, 27\% dry associated and 34\% indifferent to seasonality. Nearly 80\% of species had estimated modes of occurrence within the seasonality range considered here. Species with lower SLA and lower wood density were more likely to occur in more seasonal sites where dry-associated species formed the majority of co-occurring species. The proportion of wet-associated species increased only after intermediate levels of seasonality. The community proportion of extreme wet-associated species decreased prominently from less to more seasonal sites. Main conclusions Dry-associated species persisted in less seasonal sites, but not vice versa. A shift toward more seasonal rainfall might favour dry-associated species and shrink the ranges of wet-associated species. Future work should assess how the intensity and duration of drought and interactions with other drivers of global change regulate the relative performance of species at more and less seasonal sites.

}, doi = {10.1111/geb.13350}, author = {Krishnadas, Meghna and Sankaran, Mahesh and Page, Navendu and Joshi, Jahnavi and Machado, Siddarth and Nataraj, Nandita and Chengappa, Sannuvanda K. and Kumar, Vijay and Kumar, Ajith and Krishnamani, Ramanathan and Hampe, Arndt} } @article {97221, title = {Seasonal forage and diet quality in two subtropical ungulates in the Himalaya}, journal = {European Journal Of Wildlife Research}, volume = {67}, year = {2021}, month = {08/2021}, abstract = {

Drastic seasonal changes in higher latitudes and altitudes impact the phenology of plant growth forms differently and thus diet of ungulates feeding on them. We examined how fecal nitrogen (N), an indicator of diet quality, varied with season against the background variation in forage biomass and N in habitats of two sympatric ungulates in subtropical Himalaya. We conducted this study in Kyongnosla Alpine Sanctuary, Sikkim, where the Himalayan goral Naemorhedus goral occurred from 3000 to 3600 m and Himalayan musk deer Moschus chrysogaster from 3300 to 4200 m. We measured biomass and N content of forbs and graminoids and browse in their habitats and proportions of monocots and dicots and N content in their fecal pellets. Seasonal variation in biomass, primarily determined by forbs, was similar in goral and musk deer habitats. Goral had a graminoid-dominated diet switching to dicots in autumn and winter. Musk deer had a dicot-dominated diet in all seasons. Fecal N in both the ungulates was higher than forage N in all seasons except spring when the latter was greater. Forage and fecal N declined sharply from spring as seasons progressed. Fecal N in goral was considerably lower than in musk deer in all seasons, probably below maintenance levels in autumn and winter. As evident from peaks and duration of high diet quality, goral is likely a capital breeder and musk deer an income breeder. Results suggest that linkages between diet and reproductive seasonality in ungulates will have important implications in face of climate change.

}, doi = {10.1007/s10344-021-01518-x}, author = {Srivastava, Tanushree and Kumar, Ajith} } @article {90237, title = {Securing biodiversity, securing our future: A national mission on biodiversity and human well-being for India}, journal = {BIOLOGICAL CONSERVATION}, volume = {253}, year = {2021}, month = {01/2021}, abstract = {

Highly populated tropical countries face tremendous pressures in reconciling the needs for improved economic security and the protection of declining biodiversity. India is no exception and its biodiversity is under severe pressure due to complex interactions among land use change, other human economic activities, and climate change. Preservation and restoration of biodiversity is perhaps the cheapest and least risky way to mitigate the impacts of threats such as climate change, diminishing food and nutritional security, declining economy, absence of affordable healthcare, rising zoonotic diseases and lack of capacity to address these issues. Here we describe a framework for biodiversity conservation - the National Mission on Biodiversity and Human Well-Being (NMBHWB) for India - which integrates biodiversity, ecosystem services, climate change, agriculture, health, bio-economy and capacity building in the realm of biodiversity science. We provide an overview of the seven Programs of the Mission which make it interdisciplinary, integrative, and comprehensive in its approach. The Mission explicitly links research with policy-making and implementation for effective management of biodiversity with sustainable development. With its emphasis on convergence and synergies among various goals, themes and project sites, the Mission will further develop new models for stakeholder consultations and co-production of knowledge. We posit that the NMBHWB will enable India to realize the United Nations Sustainable Development Goals and Targets while advancing India{\textquoteright}s commitments to the Paris Agreement on climate change and other international environmental conventions and treaties.

}, doi = {10.1016/j.biocon.2020.108867}, author = {Bawa, Kamaljit S and Sengupta, Asmita and Chavan, Vishwas and Chellam, Ravi and Ganesan, R. and Krishnaswamy, Jagdish and Mathur, Vinod B. and Nawn, Nandan and Olsson, Shannon B and Pandit, Nitin and Quader, Suhel and Rajagopal, Prabhakar and Ramakrishnan, Uma and Ravikanth, G. and Sankaran, Mahesh and Shankar, Darshan and Seidler, Reinmar and Shaanker, R. Uma and Vanak, Abi Tamim} } @article {93657, title = {Seed fates of four rainforest tree species in the fragmented forests of Anamalais in the southern Western Ghats, India}, journal = {ACTA OECOLOGICA-INTERNATIONAL JOURNAL OF ECOLOGY}, year = {2021}, month = {05/2021}, abstract = {

Seed predation is one of the key ecosystem processes governing the plant population and community structure in forests. Forest fragmentation and habitat loss have been shown to affect seed predation, leading to altered tree recruitment. However, the effects of fragmentation and habitat loss on seed predation are highly variable and context-specific, with limited information from South Asia. For four rainforest tree species in a production landscape of tea and coffee, we examined the influence of forest type (benchmark, N = 3, and fragmented, N = 5, forests) and seed size on the proportion of seeds, 1) predated by vertebrate seed predators, 2) predated by invertebrate seed predators, and 3) removed by vertebrate seed predators. The seed fates were tracked by placing the seeds in four 1 x 1 m plots under the canopy of the tree (N \>= 11 individuals per tree species and 48 trees overall), and camera traps were placed under a subset of trees (N = 29, trap-nights = 712). Overall, we recorded nine species of seed predators, and that the seed predator species composition differed among the four tree species. However, there was no significant difference in either seed predator species composition or their visitations across the forest types. The seeds were more likely to be predated (on average 6\% higher predation) by vertebrate seed predators in the fragments than in the benchmark forests. Medium-seeded species were more likely to be predated by vertebrate seed predators than large-seeded species (on average 41\% higher predation). Invertebrate seed predation and seed removal by vertebrate seed predators had a weak relationship with forest type, with higher invertebrate seed predation in the fragments and higher seed removal in the benchmark forests. With altered seed dispersal patterns resulting from habitat fragmentation and habitat loss, differential seed predation can alter regeneration patterns, thereby influencing adult tree communities in fragmented forests.

}, doi = {10.1016/j.actao.2020.103698}, author = {Gopal, Abhishek and Mudappa, Divya and Raman, TRS and Naniwadekar, Rohit} } @article {92883, title = {Self-Reproduction and Darwinian Evolution in Autocatalytic Chemical Reaction Systems.}, journal = {Life (Basel)}, volume = {11}, year = {2021}, month = {2021 Apr 01}, abstract = {

Understanding the emergence of life from (primitive) abiotic components has arguably been one of the deepest and yet one of the most elusive scientific questions. Notwithstanding the lack of a clear definition for a living system, it is widely argued that heredity (involving self-reproduction) along with compartmentalization and metabolism are key features that contrast living systems from their non-living counterparts. A minimal living system may be viewed as "a self-sustaining chemical system capable of Darwinian evolution". It has been proposed that autocatalytic sets of chemical reactions (ACSs) could serve as a mechanism to establish chemical compositional identity, heritable self-reproduction, and evolution in a minimal chemical system. Following years of theoretical work, autocatalytic chemical systems have been constructed experimentally using a wide variety of substrates, and most studies, thus far, have focused on the demonstration of chemical self-reproduction under specific conditions. While several recent experimental studies have raised the possibility of carrying out some aspects of experimental evolution using autocatalytic reaction networks, there remain many open challenges. In this review, we start by evaluating theoretical studies of ACSs specifically with a view to establish the conditions required for such chemical systems to exhibit self-reproduction and Darwinian evolution. Then, we follow with an extensive overview of experimental ACS systems and use the theoretically established conditions to critically evaluate these empirical systems for their potential to exhibit Darwinian evolution. We identify various technical and conceptual challenges limiting experimental progress and, finally, conclude with some remarks about open questions.

}, issn = {2075-1729}, doi = {10.3390/life11040308}, author = {Ameta, Sandeep and Matsubara, Yoshiya J and Chakraborty, Nayan and Krishna, Sandeep and Thutupalli, Shashi} } @article {88402, title = {Sex differences in the delayed impact of acute stress on the amygdala.}, journal = {Neurobiol Stress}, volume = {14}, year = {2021}, month = {2021 May}, pages = {100292}, abstract = {

There is accumulating evidence that stress triggers specific temporal patterns of morphological plasticity in the amygdala, a brain area that plays a pivotal role in the debilitating emotional symptoms of stress-related psychiatric disorders. Acute immobilization stress is known to cause a delayed increase in the density of dendritic spines on principal neurons in the basolateral amygdala (BLA) of rats. These neuronal changes are also accompanied by a delayed enhancement in anxiety-like behavior. However, these earlier studies used male rats, and the delayed behavioral and synaptic effects of acute stress on the BLA of female rats remain unexplored. Here, using whole-cell recordings in rat brain slices, we find that a single exposure to 2-h immobilization stress leads to an increase, 10 days later, in the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded from lateral amygdala (LA) principal neurons in male rats. Further, acute stress also causes a reduction in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in LA neurons 10 days after acute stress. In striking contrast, excitatory and inhibitory synaptic transmission in the LA of female rats does not exhibit any delayed change despite exposure to the same acute stress. Finally, we examined the functional impact of these contrasting synaptic changes at the behavioral level. Male rats exhibit a delayed increase in anxiety-like behavior on the elevated plus-maze 10 days after acute stress. However, the same stress does not lead to a delayed anxiogenic effect in female rats. Together, these results demonstrate that the delayed modulation of the balance of synaptic excitation and inhibition in the amygdala, as well as anxiety-like behavior, differ between males and females. These findings provide a framework, across biological scales, for analyzing how affective symptoms of stress disorders vary between the sexes.

}, issn = {2352-2895}, doi = {10.1016/j.ynstr.2020.100292}, author = {Gupta, Kanika and Chattarji, Sumantra} } @article {97218, title = {Sphingolipid metabolism during TLR4-mediated macrophage activation.}, journal = {Br J Pharmacol}, year = {2021}, month = {2021 Aug 06}, abstract = {

Macrophage activation in response to stimulation of Toll-like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulate the inflammatory response. TLR4-mediated pro-inflammatory macrophage activation is characterised by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompany classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here we review the importance of TLR4-mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4-driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasise the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro-inflammatory and pro-resolution phases of LPS/TLR4 activation in macrophages.

}, issn = {1476-5381}, doi = {10.1111/bph.15642}, author = {Olona, Antoni and Hateley, Charlotte and Muralidharan, Sneha and Wenk, Markus R and Torta, Federico and Behmoaras, Jacques} } @article {95906, title = {Strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors.}, journal = {PLoS Pathog}, volume = {17}, year = {2021}, month = {2021 Jul 12}, pages = {e1009706}, abstract = {

Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in RBD traffic via both CG and clathrin-mediated endocytosis. Endosomal acidification inhibitors like BafilomycinA1 and NH4Cl, which inhibit the CG pathway, reduce the uptake of RBD and impede Spike-pseudoviral infection in both AGS and AGS-ACE2 cells. The inhibition by BafilomycinA1 was found to be distinct from Chloroquine which neither affects RBD uptake nor alters endosomal pH, yet attenuates Spike-pseudovirus entry. By screening a subset of FDA-approved inhibitors for functionality similar to BafilomycinA1, we identified Niclosamide as a SARS-CoV-2 entry inhibitor. Further validation using a clinical isolate of SARS-CoV-2 in AGS-ACE2 and Vero cells confirmed its antiviral effect. We propose that Niclosamide, and other drugs which neutralize endosomal pH as well as inhibit the endocytic uptake, could provide broader applicability in subverting infection of viruses entering host cells via a pH-dependent endocytic pathway.

}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1009706}, author = {Prabhakara, Chaitra and Godbole, Rashmi and Sil, Parijat and Jahnavi, Sowmya and Gulzar, Shah-E-Jahan and van Zanten, Thomas S and Sheth, Dhruv and Subhash, Neeraja and Chandra, Anchal and Shivaraj, Akshatha and Panikulam, Patricia and U, Ibrahim and Nuthakki, Vijay Kumar and Puthiyapurayil, Theja Parassini and Ahmed, Riyaz and Najar, Ashaq Hussain and Lingamallu, Sai Manoz and Das, Snigdhadev and Mahajan, Bhagyashri and Vemula, Praveen and Bharate, Sandip B and Singh, Parvinder Pal and Vishwakarma, Ram and Guha, Arjun and Sundaramurthy, Varadharajan and Mayor, Satyajit} } @article {93057, title = {Stress enhances hippocampal neuronal synchrony and alters ripple-spike interaction.}, journal = {Neurobiol Stress}, volume = {14}, year = {2021}, month = {2021 May}, pages = {100327}, abstract = {

Adverse effects of chronic stress include anxiety, depression, and memory deficits. Some of these stress-induced behavioural deficits are mediated by impaired hippocampal function. Much of our current understanding about how stress affects the hippocampus has been derived from post-mortem analyses of brain slices at fixed time points. Consequently, neural signatures of an ongoing stressful experiences in the intact brain of awake animals and their links to later hippocampal dysfunction remain poorly understood. Further, no information is available on the impact of stress on sharp-wave ripples (SPW-Rs), high frequency oscillation transients crucial for memory consolidation. Here, we used tetrode recordings to analyze the dynamic impact of 10 days of immobilization stress on neural activity in area CA1 of mice. While there was a net decrease in pyramidal cell activity in stressed animals, a greater fraction of CA1 spikes occurred specifically during sharp-wave ripples, resulting in an increase in neuronal synchrony. After repeated stress some of these alterations were visible during rest even in the absence of stress. These findings offer new insights into stress-induced changes in ripple-spike interactions and mechanisms through which chronic stress may interfere with subsequent information processing.

}, issn = {2352-2895}, doi = {10.1016/j.ynstr.2021.100327}, author = {Tomar, Anupratap and Polygalov, Denis and Chattarji, Sumantra and McHugh, Thomas J} } @article {103404, title = {Stressed rats fail to exhibit avoidance reactions to innately aversive social calls.}, journal = {Neuropsychopharmacology}, year = {2021}, month = {2021 Nov 30}, abstract = {

Disruptions in amygdalar function, a brain area involved in encoding emotionally salient information, has been implicated in stress-related affective disorders. Earlier animal studies on the behavioral consequences of stress-induced abnormalities in the amygdala focused on learned behaviors using fear conditioning paradigms. If and how stress affects unconditioned, innate fear responses to ethologically natural aversive stimuli remains unexplored. Hence, we subjected rats to aversive ultrasonic vocalization calls emitted on one end of a linear track. Unstressed control rats exhibited a robust avoidance response by spending more time away from the source of the playback calls. Unexpectedly, prior exposure to chronic immobilization stress prevented this avoidance reaction, rather than enhancing it. Further, this stress-induced impairment extended to other innately aversive stimuli, such as white noise and electric shock in an inhibitory avoidance task. However, conditioned fear responses were enhanced by the same stress. Inactivation of the basolateral amygdala (BLA) in control rats prevented this avoidance reaction evoked by the playback. Consistent with this, analysis of the immediate early gene cFos revealed higher activity in the BLA of control, but not stressed rats, after exposure to the playback. Further, in vivo recordings in freely behaving control rats exposed to playback showed enhanced theta activity in the BLA, which also was absent in stressed rats. These findings offer a new framework for studying stress-induced alterations in amygdala-dependent maladaptive responses to more naturally threatening and emotionally relevant social stimuli. The divergent impact of stress on defensive responses--impaired avoidance responses together with increased conditioned fear--also has important implications for models of learned helplessness and depression.

}, issn = {1740-634X}, doi = {10.1038/s41386-021-01230-z}, author = {Shukla, Ashutosh and Chattarji, Sumantra} } @article {96416, title = {Structural basis for the hyperthermostability of an archaeal enzyme induced by succinimide formation.}, journal = {Biophys J}, year = {2021}, month = {2021 Jul 21}, abstract = {

Stability of proteins from hyperthermophiles (organisms existing under boiling water conditions) enabled by a reduction of conformational flexibility is realized through various mechanisms. A succinimide (SNN) arising from the post-translational cyclization of the side chains of aspartyl/asparaginyl residues with the backbone amide -NH of the succeeding residue would restrain the torsion angle Ψ and can serve as a new route for hyperthermostability. However, such a succinimide is typically prone to hydrolysis, transforming to either an aspartyl or β-isoaspartyl residue. Here, we present the crystal structure of Methanocaldococcus jannaschii glutamine amidotransferase (MjGATase) and using enhanced sampling molecular dynamics simulations, address the mechanism of its increased thermostability, up to 100 C, imparted by an unexpectedly stable succinimidyl residue (SNN) at position 109. The stability of SNN109 to hydrolysis is seen to arise from its electrostatic shielding by the side chain carboxylate group of its succeeding residue Asp110 as well as through n{\textrightarrow}π interactions between SNN109 and its preceding residue Glu108, both of which prevent water access to SNN. The stable succinimidyl residue induces the formation of an α-turn structure involving 13-atom hydrogen bonding which locks the local conformation, reducing protein flexibility. The destabilization of the protein upon replacement of SNN with a Φ-restricted prolyl residue highlights the specificity of the succinimidyl residue in imparting hyperthermostability to the enzyme. The conservation of succinimide-forming tripeptide sequence (E(N/D)(E/D)) in several archaeal GATases strongly suggests an adaptation of this otherwise detrimental post-translational modification as a harbinger of thermostability.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2021.07.014}, author = {Dongre, Aparna Vilas and Das, Sudip and Bellur, Asutosh and Kumar, Sanjeev and Chandrashekarmath, Anusha and Karmakar, Tarak and Balaram, Padmanabhan and Balasubramanian, Sundaram and Balaram, Hemalatha} } @article {99938, title = {Structural Characterization of the Cooperativity of Unfolding of a Heterodimeric Protein Using Hydrogen Exchange-Mass Spectrometry.}, journal = {J Mol Biol}, year = {2021}, month = {2021 Sep 23}, pages = {167268}, abstract = {

Little is known about how the sequence of structural changes in one chain of a heterodimeric protein is coupled to those in the other chain during protein folding and unfolding reactions, and whether individual secondary structural changes in the two chains occur in one or many coordinated steps. Here, the unfolding mechanism of a small heterodimeric protein, double chain monellin, has been characterized using hydrogen exchange-mass spectrometry. Transient structure opening, which enables HX, was found to be describable by a five state N <-> I <-> I <-> I <-> U mechanism. Structural changes occur gradually in the first three steps, and cooperatively in the last step. β strands 2, 4 and 5, as well as the α-helix undergo transient unfolding during all three non-cooperative steps, while β1 and the two loops on both sides of the helix undergo transient unfolding during the first two steps. In the absence of GdnHCl, only β3 in chain A of the protein unfolds during the last cooperative step, while in the presence of 1 M GdnHCl, not only β3, but also β2 in chain B unfolds cooperatively. Hence, the extent of cooperative structural change and size of the cooperative unfolding unit increase when the protein is destabilized by denaturant. The naturally evolved two-chain variant of monellin folds and unfolds in a more cooperative manner than does a single chain variant created artificially, suggesting that increasing folding cooperativity, even at the cost of decreasing stability, may be a driving force in the evolution of proteins.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2021.167268}, author = {Bhattacharjee, Rupam and Udgaonkar, Jayant B} } @article {94675, title = {Super-resolution visualization and modeling of human chromosomal regions reveals cohesin-dependent loop structures.}, journal = {Genome Biol}, volume = {22}, year = {2021}, month = {2021 May 11}, pages = {150}, abstract = {

BACKGROUND: The 3D organization of the chromatin fiber in cell nuclei plays a key role in the regulation of gene expression. Genome-wide techniques to score DNA-DNA contacts, such as Hi-C, reveal the partitioning of chromosomes into epigenetically defined active and repressed compartments and smaller "topologically associated" domains. These domains are often associated with chromatin loops, which largely disappear upon removal of cohesin. Because most Hi-C implementations average contact frequencies over millions of cells and do not provide direct spatial information, it remains unclear whether and how frequently chromatin domains and loops exist in single cells.

RESULTS: We combine 3D single-molecule localization microscopy with a low-cost fluorescence labeling strategy that does not denature the DNA, to visualize large portions of single human chromosomes in situ at high resolution. In parallel, we develop multi-scale, whole nucleus polymer simulations, that predict chromatin structures at scales ranging from 5\ kb up to entire chromosomes. We image chromosomes in G1 and M phase and examine the effect of cohesin on interphase chromatin structure. Depletion of cohesin leads to increased prevalence of loose chromatin stretches, increased gyration radii, and reduced smoothness of imaged chromatin regions. By comparison to model predictions, we estimate that 6-25 or more purely cohesin-dependent chromatin loops coexist per megabase of DNA in single cells, suggesting that the vast majority of the genome is enclosed in loops.

CONCLUSION: Our results provide new constraints on chromatin structure and showcase an affordable non-invasive approach to study genome organization in single cells.

}, issn = {1474-760X}, doi = {10.1186/s13059-021-02343-w}, author = {Hao, Xian and Parmar, Jyotsana J and Lelandais, Beno{\^\i}t and Aristov, Andrey and Ouyang, Wei and Weber, Christian and Zimmer, Christophe} } @article {88159, title = {SWITCHES: Searchable web interface for topologies of CHEmical switches.}, journal = {Bioinformatics}, year = {2021}, month = {2021 Jan 18}, abstract = {

: Bistable biochemical switches are key motifs in cellular state decisions and long-term storage of cellular {\textquoteright}memory{\textquoteright}. There are a few known biological switches that have been well characterized, however these examples are insufficient for systematic surveys of properties of these important systems. Here we present a resource of all possible bistable biochemical reaction networks with up to 6 reactions between 3 molecules, and 3 reactions between 4 molecules. Over 35,000 reaction topologies were constructed by identifying unique combinations of reactions between a fixed number of molecules. Then, these topologies were populated with rates within a biologically realistic range. The Searchable Web Interface for Topologies of CHEmical Switches (SWITCHES, https://switches.ncbs.res.in) provides a bistability and parameter analysis of over 7 million models from this systematic survey of chemical reaction space. This database will be useful for theoreticians interested in analyzing stability in chemical systems and also experimentalists for creating robust synthetic biological switches.

AVAILABILITY AND IMPLEMENTATION: Freely available on the web at https://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz, and Apache, with all major browsers supported.

}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btab006}, author = {HarshaRani, G V and Moza, S and Ramakrishnan, N and Bhalla, U S} } @article {104889, title = {On the systematics and the phylogenetic position of the poorly known, montane dragon-lizard species Pseudocalotes austeniana (Annandale, 1908) (Squamata, Agamidae, Draconinae)}, journal = {Evolutionary Systematics}, volume = {5}, year = {2021}, month = {06/2021}, pages = {141-150 }, abstract = {

The montane agamid species Pseudocalotes austeniana has had a complicated taxonomic history, as the species was initially described as a member of the genus Salea Gray, 1845. Later, the species was placed in a monotypic genus Mictopholis Smith, 1935, which was erected only to include this species; however, the species was later on transferred to the genus Pseudocalotes Fitzinger, 1843, owing to the morphological similarities, and lack of strong characters to diagnose the genus Mictopholis. Nonetheless, its precise phylogenetic and systematic position has remained unresolved due to the lack of molecular sequence data. During a herpetological expedition to Arunachal Pradesh, specimens of P. austeniana were collected from the hills near the type locality. The mitochondrial 16S rRNA, ND2 and ND4, and the nuclear RAG1 regions were subjected to molecular phylogenetics. Maximum Likelihood and Bayesian Inference gene trees revealed that P. austeniana is a member of the subfamily Draconinae. The analyses showed that the genus Pseudocalotes is polyphyletic, and P. austeniana was embedded within the genus Japalura Gray, 1853 sensu stricto. We here, thus, propose to transfer the species P. austeniana to the genus Japlaura, as Japalura austeniana comb. nov. Biogeographic and evolutionary significance of the findings are discussed.

}, doi = {10.3897/evolsyst.5.67137}, author = {Gowande, Gaurang and Bhosale, Harshal and Phansalkar, Pushkar and Sawant, Mandar and Mirza, Zeeshan A} } @article {92877, title = {A tale of two rhythms: Locked clocks and chaos in biology.}, journal = {Cell Syst}, volume = {12}, year = {2021}, month = {2021 Apr 21}, pages = {291-303}, abstract = {

The fundamental mechanisms that control and regulate biological organisms exhibit a surprising level of complexity. Oscillators are perhaps the simplest motifs that produce time-varying dynamics and are ubiquitous in biological systems. It is also known that such biological oscillators interact with each other-for instance, circadian oscillators affect the cell cycle, and somitogenesis clock proteins in adjacent cells affect each other in developing embryos. Therefore, it is vital to understand the effects that can emerge from non-linear interaction between oscillations. Here, we show how oscillations typically arise in biology and take the reader on a tour through the great variety in dynamics that can emerge even from a single pair of coupled oscillators. We explain how chaotic dynamics can emerge and outline the methods of detecting this in experimental time traces. Finally, we discuss the potential role of such complex dynamical features in biological systems.

}, issn = {2405-4720}, doi = {10.1016/j.cels.2021.03.003}, author = {Heltberg, Mathias L and Krishna, Sandeep and Kadanoff, Leo P and Jensen, Mogens H} } @article {100629, title = {Taxonomic notes on two jumping spider species of the genus Epocilla Thorell, 1887 (Araneae: Salticidae: Chrysillini) from India and Pakistan}, journal = {ARTHROPODA SELECTA }, volume = {30}, year = {2021}, month = {06/2021}, pages = {221-229}, chapter = {2}, abstract = {

The types of Marpissa tigrina Tikader, 1965 and M. kalapani Tikader, 1977 that are kept in the National Zoological collection, Zoological Survey of India (Kolkata) are re-examined and illustrated. A new combination, Epocilla aura (Dyal, 1935) comb.n. (ex. Thiania), is proposed and three new synonyms are established: Epocilla pakhtunkhwa Ali et Maddison, 2018 syn.n. and Marpissa tigrina Tikader, 1965 syn.n. with E. aura, and Marpissa kalapani Tikader, 1977 syn.n. with Epocilla calcarata (Karsch, 1880). The distributional records of these species from India and Pakistan are mapped.

}, author = {Caleb, John T. D. and Sanap, Rajesh V and Prajapati, Dhruv A. and Bambhaniya, Prakash} } @article {88611, title = {Temporal and spatial foraging patterns of three Asian honey bee species in Bangalore, India}, journal = {Apidologie }, year = {2021}, month = {02/21}, abstract = {

Honey bees (genus Apis) are important pollinators in Asian tropical agricultural and natural ecosystems, yet the Asian species remain vastly understudied compared to the European honey bee, Apis mellifera. We studied the temporal and spatial foraging patterns of three co-occurring Asian honey bee species in Bangalore, India, to gain a better understanding of how they coexist. We found evidence for temporal resource partitioning, with Apis cerana having activity peaks in the early mornings, Apis florea initiating foraging later in the day, and Apis dorsata having the potential to do much of its foraging activity at night, even when the moon is not yet up. Apart from the established species differences in foraging ranges, we found limited evidence of spatial partitioning of the landscape. Although individual colonies foraging in parallel often focused their foraging effort on different patches, all three species preferred foraging in cultivated garden areas to seminatural or urban areas. These observations add to the growing evidence for a key role of gardens as foraging habitat for bees in cities.

}, doi = {10.1007/s13592-020-00839-1}, author = {Young, A.M. and Kohl, P.L. and Rutschmann, B. and teffen-Dewenter, I and Brockmann, A} } @article {99109, title = {Testing the super-enhancer concept.}, journal = {Nat Rev Genet}, year = {2021}, month = {2021 Sep 03}, issn = {1471-0064}, doi = {10.1038/s41576-021-00398-w}, author = {Blobel, Gerd A and Higgs, Douglas R and Mitchell, Jennifer A and Notani, Dimple and Young, Richard A} } @article {92220, title = {Toxicity, behavioural and biochemical effect of Piper betle L. essential oil and its constituents against housefly, Musca domestica L.}, journal = {Pestic Biochem Physiol}, volume = {174}, year = {2021}, month = {05/2021}, abstract = {

Housefly, Musca domestica L. is a pest of public health importance and is responsible for spreading diseases like typhoid, diarrhoea, plague etc. Indiscriminate reliance on synthetic insecticides has led to development of insecticide resistance and ill effect to humans and nontarget animals. This demands an alternative and safer pest control option. This study evaluates the biological effect of Piper betle L essential oil and its constituent eugenol, eugenol acetate, and β - caryophyllene on the housefly. The major components present in P. betel EO were safrole (44.25\%), eugenol (5.16\%), β -caryophyllene (5.98\%), β -selinene (5.93\%), α-selinene (5.27\%) and eugenol acetate (9.77\%). Eugenol caused 4.5fold higher ovicidal activity (EC50 86.99 μg/ml) than P. betle EO (EC50 390.37 μg/ml). Eugenol caused fumigant toxicity to adults (LC50 88.38 mg/dm3). On contact toxicity by topical application, eugenol acetate, eugenol and β-caryophyllene caused higher mortality to larval and adult stages than EO. FESEM (Field Emission Scanning Electron Microscope) images reveal that exposure to P. betle EO causes the shrinkage of the larval cuticle. Both EO and eugenol induced the detoxifying enzymes Carboxyl esterase (Car E) and Glutathione S - transferases (GST) in larvae and adults. EO and eugenol at 0.2\% caused effective repellence and oviposition deterrence to M. domestica adults and this merits their use as alternative strategy to manage M. domestica.

}, doi = {10.1016/j.pestbp.2021.104804}, author = {Subaharan, K and Senthoorraja, R and Manjunath, S and Thimmegowda, GG and Pragadheesh, VS and Bakthavatsalam, N and Mohan, MG and Senthil-Nathan, S and David, KJ and Basavarajappa, S and Ballal, C} } @article {94156, title = {Tracking mitochondrial density and positioning along a growing neuronal process in individual neuron using a long-term growth and imaging microfluidic device.}, journal = {eNeuro}, year = {2021}, month = {2021 May 21}, abstract = {

The long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and sub-cellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show inter-animal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in sub-cellular events such as organelle positions, we developed a microfluidic device to feed and immobilize for high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal process Sub-cellular imaging of an individual neuron in multiple animals, over 36 hours in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase in the accumulation of synaptic vesicles at synapses. Long-term imaging of individual touch receptor neurons shows that the addition of new mitochondria takes place along the entire neuronal process length at a rate of \~{}0.6 mitochondria per hour. The threshold for the addition of a new mitochondrion occurs when the average separation between the two pre-existing mitochondria exceeds 24 {\textmu}m. Our assay provides a new opportunity to move beyond simple observations obtained from assays to allow the discovery of genes that regulate positioning of mitochondria in neurons.Axonal transport of mitochondria is required for the normal function and health of a developing animal with continuously growing axonal processes. Existing technologies are unable to monitor the addition of a new mitochondrion in a growing axon , as it requires continuous or intermittent tracking of the same individual neuron over several hours to days. We have developed a microfluidic device that enables long-term high-resolution imaging of individual in an anesthetic-free setting. Using this device, we observe that the addition of a new mitochondrion can occur anywhere along the entire neuronal process, likely mediated by actively transported mitochondria, and at docking sites that occur with high probability when the separation between adjacent mitochondria crosses 24 {\textmu}m threshold.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0360-20.2021}, author = {Mondal, Sudip and Dubey, Jyoti and Awasthi, Anjali and Sure, Guruprasad Reddy and Vasudevan, Amruta and Koushika, Sandhya P} } @article {95517, title = {Trends in Wildlife Connectivity Science from the Biodiverse and Human-Dominated South Asia}, journal = {JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE}, year = {2021}, month = {06/2021}, abstract = {

The threat of habitat fragmentation and population isolation looms large over much of biodiversity in this human-dominated epoch. Species-rich South Asia is made particularly vulnerable by its high human density and anthropogenic habitat modification. Therefore, reliably estimating wildlife connectivity and the factors underpinning it become crucial in mitigating extinction risk due to isolation. We analysed peer-reviewed literature on connectivity and corridors for terrestrial mammals in South Asia to identify trends in connectivity research. We identify key research gaps and highlight future directions that may aid efforts to robustly study connectivity. We found a significant bias towards charismatic megafauna and their habitats. Methodologically, although we observed a range of approaches reflecting some of the advances and innovations in the field, several studies lacked data on animal movement/behaviour, leading to potentially biased inferences of how species disperse through human-modified landscapes. New avenues for connectivity research, though currently under-explored in South Asia, offer alternatives to the heavily used but less-reliable habitat suitability models. We highlight the advantages of landscape genetic methods that reflect effective dispersal and are made feasible through non-invasive and increasingly more cost-effective sampling methods. We also identify important gaps or areas of focus that need to be addressed going forward, including accounting for animal movement/behaviour, human impacts and landscape change for dynamic and adaptive connectivity planning for the future.

}, doi = {10.1007/s41745-021-00240-6}, author = {Thatte, Prachi and Tyagi, Abhinav and Neelakantan, Amrita and Natesh, Meghana and Sen, Mihika and Thekaekara, Tarsh} } @article {93661, title = {The truth about scats and dogs: Next-generation sequencing and spatial capture-recapture models offer opportunities for conservation monitoring of an endangered social canid}, journal = {BIOLOGICAL CONSERVATION}, year = {2021}, month = {04/2021}, abstract = {

Obtaining accurate population counts of endangered species is central to conservation biology, with implications for gaining ecological insights, informing management strategies, and judicial use of conservation funds. Despite decades of progress in methodological developments in the realm of population ecology, reliable density estimates are unavailable for many species of conservation concern. The dhole (Asiatic wild dog Cuon alpinus) is one such endangered large carnivore found in the tropical forests of south and southeast Asia. Here, we (i) develop next-generation sequencing resources to identify individual dholes from genetic samples, (ii) apply these methods to identify individuals in the wild, from scat (fecal) samples collected through systematic field surveys and (iii) generate reliable estimates of dhole densities in Wayanad Wildlife Sanctuary (Western Ghats, India) using Spatial Capture-Recapture {\textquoteright}SCR{\textquoteright} models. We estimate dhole densities to be 12-14.2 individuals/100 sq. km based on a set of SCR models, with similar to 50 individuals within Wayanad{\textquoteright}s administrative boundary. Our study presents a methodological improvement in generating population estimates of an important apex predator while also offering ecologically informative insights on a species in dire need of science-based management efforts. Replicating this study across connected reserves and over time can serve as a unified framework for understanding population dynamics, population structures, landscape connectivity and metapopulation-level conservation requirements. We propose that the approach presented here may be adopted as an economically and logistically feasible protocol for conservation monitoring of dholes and other ecologically important species plagued by similar issues of data-deficiency, and insufficient funding and resources.

}, doi = {10.1016/j.biocon.2021.109028}, author = {Srivathsa, Arjun and Rodrigues, Ryan G and Toh, Kok Ben and Zachariah, Arun and Taylor, Ryan W and Oli, Madan K and Ramakrishnan, Uma} } @article {105154, title = {A Tunable Palette of Molecular Rotors Allows Multicolor, Ratiometric Fluorescence Imaging and Direct Mapping of Mitochondrial Heterogeneity.}, journal = {ACS Appl Bio Mater}, volume = {4}, year = {2021}, month = {2021 May 17}, pages = {4361-4372}, abstract = {

Environment-sensitive molecular probes offer the potential for a comprehensive mapping of the complex cellular milieu. We present here a radically new strategy of multiplexing highly sensitive, spectrally tuned fluorescent dyes for sensing cellular microenvironment. To achieve this multicolor, ratiometric cellular imaging, we first developed a series of highly sensitive, tunable molecular rotors for mitochondrial imaging, with emission wavelengths spanning the visible spectrum. These fluorogenic merocyanine dyes are all sensitive to solvent viscosity despite distinctive photophysical features. Our results show that merocyanine dyes can show a rotor-like behavior despite significant changes to the conventional donor-acceptor or push-pull scaffolds, thereby revealing conserved features of rotor dye chemistry. Developing closely related but spectrally separated dyes that have distinct response functions allows us to do "two-color, two-dye" imaging of the mitochondrial microenvironment. Our results with multidye, combinatorial imaging provide a direct visualization of the intrinsic heterogeneity of the mitochondrial microenvironment. The overall mitochondrial microenvironment (including contributions from local membrane order) as reported through two-color fluorescence "ratio" changes of multiplexed rotor dyes shows dynamic heterogeneity with distinct spatiotemporal signatures that evolve over time and respond to chemical perturbations. Our results offer a powerful illustration of how multiplexed dye imaging allows the quantitative imaging of mitochondrial membrane order and cellular microenvironment.

}, issn = {2576-6422}, doi = {10.1021/acsabm.1c00135}, author = {Raja, Sufi O and Sivaraman, Gandhi and Biswas, Sayan and Singh, Gaurav and Kalim, Fouzia and Kandaswamy, Ponnuvel and Gulyani, Akash} } @article {96102, title = {Tyramine 1 Receptor Distribution in the Brain of Corbiculate Bees Points to a Conserved Function.}, journal = {Brain Behav Evol}, year = {2021}, month = {2021 Jul 15}, pages = {1-13}, abstract = {

Sucrose represents an important carbohydrate source for most bee species. In the Western honeybee (Apis mellifera) it was shown that individual sucrose responsiveness correlates with the task performed in the colony, supporting the response threshold theory which states that individuals with the lowest threshold for a task-associated stimuli will perform the associated task. Tyramine was shown to modulate sucrose responsiveness, most likely via the tyramine 1 receptor. This receptor is located in brain areas important for the processing of gustatory stimuli. We asked whether the spatial expression pattern of the tyramine 1 receptor is a unique adaptation of honeybees or if its expression represents a conserved trait. Using a specific tyramine receptor 1 antibody, we compared the spatial expression of this receptor in the brain of different corbiculate bee species, including eusocial honeybees, bumblebees, stingless bees, and the solitary bee Osmia bicornis as an outgroup. We found a similar labeling pattern in the mushroom bodies, the central complex, the dorsal lobe, and the gnathal ganglia, indicating a conserved receptor expression. With respect to sucrose responsiveness this result is of special importance. We assume that the tyramine 1 receptor expression in these neuropiles provides the basis for modulation of sucrose responsiveness. Furthermore, the tyramine 1 receptor expression seems to be independent of size, as labeling is similar in bee species that differ greatly in their body size. However, the situation in the optic lobes appears to be different. Here, the lobula of stingless bees is clearly labeled by the tyramine receptor 1 antibody, whereas this labeling is absent in other species. This indicates that the regulation of this receptor is different in the optic lobes, while its function in this neuropile remains unclear.

}, issn = {1421-9743}, doi = {10.1159/000517014}, author = {Thamm, Markus and Wagler, Katharina and Brockmann, Axel and Scheiner, Ricarda} } @article {102260, title = {UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons}, journal = { Genetics}, volume = {219}, year = {2021}, month = {11/2021}, pages = {iyab139}, abstract = {

Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. Our study shows that UNC-16, a Caenorhabditis elegans JIP3 homolog, inhibits axonal regeneration by regulating initiation and rate of regrowth. This occurs through the inhibition of the regeneration-promoting activity of the long isoform of DLK-1 and independently of the inhibitory short isoform of DLK-1. We show that UNC-16 promotes DLK-1 punctate localization in a concentration-dependent manner limiting the availability of the long isoform of DLK-1 at the cut site, minutes after injury. UNC-16 negatively regulates actin dynamics through DLK-1 and microtubule dynamics partially via DLK-1. We show that post-injury cytoskeletal dynamics in unc-16 mutants are also partially dependent on CEBP-1. The faster regeneration seen in unc-16 mutants does not lead to functional recovery. Our data suggest that the inhibitory control by UNC-16 and the short isoform of DLK-1 balances the intrinsic growth-promoting function of the long isoform of DLK-1 in vivo. We propose a model where UNC-16{\textquoteright}s inhibitory role in regeneration occurs through both a tight temporal and spatial control of DLK-1 and cytoskeletal dynamics.

}, doi = {10.1093/genetics/iyab139 }, author = {Kulkarni, SS and Sabharwal, V. and Sheoran, S. and Basu, A. and Matsumoto, K. and Hisamoto, N. and Ghosh-Roy, A. and Koushika, Sandhya P} } @article {97223, title = {Understanding the Folding Mediated Assembly of the Bacteriophage MS2 Coat Protein Dimers.}, journal = {J Phys Chem B}, year = {2021}, month = {2021 Aug 02}, abstract = {

The capsids of RNA viruses such as MS2 are great models for studying protein self-assembly because they are made almost entirely of multiple copies of a single coat protein (CP). Although CP is the minimal repeating unit of the capsid, previous studies have shown that CP exists as a homodimer (CP2) even in an acid-disassembled system, indicating that CP2 is an obligate dimer. Here, we investigate the molecular basis of this obligate dimerization using coarse-grained structure-based models and molecular dynamics simulations. We find that, unlike monomeric proteins of similar size, CP populates a single partially folded ensemble whose "foldedness" is sensitive to denaturing conditions. In contrast, CP2 folds similarly to single-domain proteins populating only the folded and the unfolded ensembles, separated by a prominent folding free energy barrier. Several intramonomer contacts form early, but the CP2 folding barrier is crossed only when the intermonomer contacts are made. A dissection of the structure of CP2 through mutant folding simulations shows that the folding barrier arises both from the topology of CP and the interface contacts of CP2. Together, our results show that CP2 is an obligate dimer because of kinetic stability, that is, dimerization induces a folding barrier and that makes it difficult for proteins in the dimer minimum to partially unfold and access the monomeric state without completely unfolding. We discuss the advantages of this obligate dimerization in the context of dimer design and virus stability.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.1c03928}, author = {Lalwani, DP and Gosavi, Shachi} } @article {96103, title = {An {\textquoteright}up{\textquoteright} oriented methionine-aromatic structural motif in SUMO is critical for its stability and activity.}, journal = {J Biol Chem}, year = {2021}, month = {2021 Jul 15}, pages = {100970}, abstract = {

Protein structural bioinformatic analyses suggest preferential associations between methionine and aromatic amino acid residues in proteins. Ab initio energy calculations highlight a conformation-dependent stabilizing interaction between the interacting sulfur-aromatic molecular pair. However, the relevance of buried methionine-aromatic motifs to protein folding and function is relatively unexplored. The Small Ubiquitin-Like Modifier (SUMO) is a β-grasp fold protein and a common post-translational modifier that affects diverse cellular processes, including transcriptional regulation, chromatin remodeling, metabolic regulation, mitosis, and meiosis. SUMO is a member of the Ubiquitin-Like (UBL) protein family. Herein, we report that a highly conserved and buried methionine-phenylalanine motif is a unique signature of SUMO proteins but absent in other homologous UBL proteins. We also detect that a specific {\textquoteright}up{\textquoteright} conformation between the methionine-phenylalanine pair of interacting residues in SUMO is critical to its β-grasp fold. The noncovalent interactions of SUMO with its ligands are dependent on the methionine-phenylalanine pair. MD simulations, NMR, and biophysical and biochemical studies suggest that perturbation of the methionine-aromatic motif disrupts native contacts, modulates noncovalent interactions, and attenuates SUMOylation activity. Our results highlight the importance of conserved orientations of Met-aromatic structural motifs inside a protein core for its structure and function.

}, issn = {1083-351X}, doi = {10.1016/j.jbc.2021.100970}, author = {Chatterjee, Kiran Sankar and Das, Ranabir} } @article {93052, title = {Using CRISPR-Cas9-based genome engineering tools in Drosophila melanogaster.}, journal = {Prog Mol Biol Transl Sci}, volume = {180}, year = {2021}, month = {2021}, pages = {85-121}, abstract = {

Drosophila melanogaster has been used as a model organism for over a century. Mutant-based analyses have been used extensively to understand the genetic basis of different cellular processes, including development, neuronal function and diseases. Most of the earlier genetic mutants and specific tools were generated by random insertions and deletion strategies and then mapped to specific genomic loci. Since all genomic regions are not equally accessible to random mutations and insertions, many genes still remain uncharacterized. Low efficiency of targeted genomic manipulation approaches that rely on homologous recombination, and difficulty in generating resources for sequence-specific endonucleases, such as ZFNs (Zinc Finger Nucleases) and TALENs (Transcription Activator-Like Effector Nucleases), could not make these gene targeting techniques very popular. However, recently RNA directed DNA endonucleases, such as CRISPR-Cas, have transformed genome engineering owing to their comparative ease, versatility, and low expense. With the added advantage of preexisting genetic tools, CRISPR-Cas-based manipulations are being extensively used in Drosophila melanogaster and simultaneously being fine-tuned for specific experimental requirements. In this chapter, I will discuss various uses of CRISPR-Cas-based genetic engineering and specific design methods in Drosophila melanogaster. I will summarize various already available tools that are being utilized in conjunction with CRISPR-Cas technology to generate specific genetic manipulation and are being optimized to address specific questions. Finally, I will discuss the future directions of Drosophila genetics research and how CRISPR-Cas can be utilized to target specific questions, addressing which has not been possible thus far.

}, issn = {1878-0814}, doi = {10.1016/bs.pmbts.2021.01.006}, author = {Trivedi, Deepti} } @article {85185, title = {Using Integrative Modeling Platform to Compute, Validate, and Archive a Model of a Protein Complex Structure.}, journal = {Protein Sci}, volume = {30}, year = {2021}, month = {2020 Nov 09}, pages = {250-261}, abstract = {

Biology is advanced by producing structural models of biological systems, such as protein complexes. Some systems are recalcitrant to traditional structure determination methods. In such cases, it may still be possible to produce useful models by integrative structure determination that depends on simultaneous use of multiple types of data. An ensemble of models that are sufficiently consistent with the data is produced by a structural sampling method guided by a data-dependent scoring function. The variation in the ensemble of models quantified the uncertainty of the structure, generally resulting from the uncertainty in the input information and actual structural heterogeneity in the samples used to produce the data. Here, we describe how to generate, assess, and interpret ensembles of integrative structural models using our open source Integrative Modeling Platform program (https://integrativemodeling.org). This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.3995}, author = {Saltzberg, Daniel J and Viswanath, Shruthi and Echeverria, Ignacia and Chemmama, Ilan E and Webb, Ben and Sali, Andrej} } @article {87007, title = {Variable interplay of UV-induced DNA damage and repair at transcription factor binding sites}, journal = {Nucleic Acids Res}, volume = {49}, year = {2021}, month = {12/2020}, pages = {891-901}, abstract = {

An abnormally high rate of UV-light related mutations appears at transcription factor binding sites (TFBS) across melanomas. The binding of transcription factors (TFs) to the DNA impairs the repair of UV-induced lesions and certain TFs have been shown to increase the rate of generation of these lesions at their binding sites. However, the precise contribution of these two elements to the increase in mutation rate at TFBS in these malignant cells is not understood. Here, exploiting nucleotide-resolution data, we computed the rate of formation and repair of UV-lesions within the binding sites of TFs of different families. We observed, at certain dipyrimidine positions within the binding site of TFs in the Tryptophan Cluster family, an increased rate of formation of UV-induced lesions, corroborating previous studies. Nevertheless, across most families of TFs, the observed increased mutation rate within the entire DNA region covered by the protein results from the decreased repair efficiency. While the rate of mutations across all TFBS does not agree with the amount of UV-induced lesions observed immediately after UV exposure, it strongly agrees with that observed after 48 h. This corroborates the determinant role of the impaired repair in the observed increase of mutation rate.

}, doi = {10.1093/nar/gkaa1219}, author = {Frigola, J and Sabarinathan, R and Gonzalez-Perez, A and Lopez-Bigas, N} } @article {89124, title = {Varying impacts of logging frequency on tree communities and carbon storage across evergreen and deciduous tropical forests in the Andaman Islands, India}, journal = {FOREST ECOLOGY AND MANAGEMENT}, year = {2021}, month = {02/20201}, abstract = {

The majority of Earth{\textquoteright}s tropical forests have been selectively logged; some on repeated occasions. Selective logging is known to affect forest structure, composition and function in various ways, but how such effects vary with logging frequency and across forest types remains unclear. In the Andaman Archipelago in India, we examined adult and pole-sized trees in baseline (unlogged since 1990s), once-logged (logged between 2007 and 2014) and twice-logged (logged in early 1990s and between 2007 and 2014) evergreen and deciduous forests, and tested whether higher logging frequency was associated with lower canopy cover, tree density, tree diversity, aboveground carbon stocks and divergence in species composition, including increased relative abundances of deciduous species in these forests. While once-logged evergreen and deciduous forests were similar to their respective baselines for most attributes assessed, and twice-logged evergreen forests had 22-24\% lower adult tree density and diversity, twice-logged deciduous forests had 17-50\% lower canopy cover, pole density, adult species diversity and above-ground carbon stocks, and 12\% higher deciduous fractions compared to the baselines. Collectively our results reveal lasting impacts of repeated selective logging, even at relative low intensity, on tree communities and carbon storage. These impacts can potentially be mitigated by reducing logging frequency and retaining unlogged patches in logged landscapes, but management must also incorporate heterogeneity in responses and recovery across different forest types. In the Andaman Islands, all forests may require more than 15-25 years between logging events, with deciduous forests potentially requiring more stringent extraction limits compared to evergreen forests.

}, doi = {10.1016/j.foreco.2020.118791}, author = {Surendra, Akshay and Osuri, A. M and Ratnam, Jayashree} } @article {99106, title = {"Viscotaxis"- Directed Migration of Mesenchymal Stem Cells in Response to Loss Modulus Gradient.}, journal = {Acta Biomater}, year = {2021}, month = {2021 Aug 29}, abstract = {

Directed cell migration plays a crucial role in physiological and pathological conditions. One important mechanical cue, known to influence cell migration, is the gradient of substrate elastic modulus (E). However, the cellular microenvironment is viscoelastic and hence the elastic property alone is not sufficient to define its material characteristics. To bridge this gap, in this study, we investigated the influence of the gradient of viscous property of the substrate, as defined by loss modulus (G) on cell migration. We cultured human mesenchymal stem cells (hMSCs) on a collagen-coated polyacrylamide gel with constant storage modulus (G) but with a gradient in the loss modulus (G). We found hMSCs to migrate from high to low loss modulus. We have termed this form of directional cellular migration as "Viscotaxis". We hypothesize that the high loss modulus regime deforms more due to creep in the long timescale when subjected to cellular traction. Such differential deformation drives the observed Viscotaxis. To verify our hypothesis, we disrupted the actomyosin contractility with myosin inhibitor blebbistatin and ROCK inhibitor Y27632, and found the directional migration to disappear. Further, such time-dependent creep of the high loss material should lead to lower traction, shorter lifetime of the focal adhesions, and dynamic cell morphology, which was indeed found to be the case. Together, findings in this paper highlight the importance of considering the viscous modulus while preparing stiffness-based substrates for the field of tissue engineering. STATEMENT OF SIGNIFICANCE: While the effect of substrate elastic modulus has been investigated extensively in the context of cell biology, the role of substrate viscoelasticity is poorly understood. This omission is surprising as our body is not elastic, but viscoelastic. Hence, the role of viscoelasticity needs to be investigated at depth in various cellular contexts. One such important context is cell migration. Cell migration is important in morphogenesis, immune response, wound healing, and cancer, to name a few. While it is known that cells migrate when presented with a substrate with a rigidity gradient, cellular behavior in response to viscoelastic gradient has never been investigated. The findings of this paper not only reveal a completely novel cellular taxis or directed migration, it also improves our understanding of cell mechanics significantly.

}, issn = {1878-7568}, doi = {10.1016/j.actbio.2021.08.039}, author = {Shirke, Pallavi Uday and Goswami, Hiya and Kumar, Vardhman and Shah, Darshan and Beri, Sarayu and Das, Siddhartha and Bellare, Jayesh and Mayor, Satyajit and Venkatesh, K V and Seth, Jyoti R and Majumder, Abhijit} } @article {92226, title = {Whirligig beetles as corralled active Brownian particles.}, journal = {J R Soc Interface}, volume = {18}, year = {2021}, month = {04/2021}, pages = {20210114}, abstract = {

We study the collective dynamics of groups of whirligig beetles Dineutus discolor (Coleoptera: Gyrinidae) swimming freely on the surface of water. We extract individual trajectories for each beetle, including positions and orientations, and use this to discover (i) a density-dependent speed scaling like v \~{} ρ-ν with ν ≈ 0.4 over two orders of magnitude in density (ii) an inertial delay for velocity alignment of approximately 13 ms and (iii) coexisting high and low-density phases, consistent with motility-induced phase separation (MIPS). We modify a standard active Brownian particle (ABP) model to a corralled ABP (CABP) model that functions in open space by incorporating a density-dependent reorientation of the beetles, towards the cluster. We use our new model to test our hypothesis that an motility-induced phase separation (MIPS) (or a MIPS like effect) can explain the co-occurrence of high- and low-density phases we see in our data. The fitted model then successfully recovers a MIPS-like condensed phase for N = 200 and the absence of such a phase for smaller group sizes N = 50, 100.

}, doi = {10.1098/rsif.2021.0114}, author = {Devereux, HL and Twomey, CR and Turner, MS and Thutupalli, Shashi} } @article {102566, title = {Wings and halteres act as coupled dual-oscillators in flies.}, journal = {Elife}, volume = {10}, year = {2021}, month = {2021 Nov 16}, abstract = {

The mechanics of Dipteran thorax is dictated by a network of exoskeletal linkages which, when deformed by the flight muscles, generate coordinated wing movements. In Diptera, the forewings power flight, whereas the hindwings have evolved into specialized structures called halteres which provide rapid mechanosensory feedback for flight stabilization. Although actuated by independent muscles, wing and haltere motion is precisely phase-coordinated at high frequencies. Because wingbeat frequency is a product of wing-thorax resonance, any wear-and-tear of wings or thorax should impair flight ability. How robust is the Dipteran flight system against such perturbations? Here, we show that wings and halteres are independently-driven, coupled oscillators. We systematically reduced the wing length in flies and observed how wing-haltere synchronization was affected. The wing-wing system is a strongly-coupled oscillator, whereas the wing-haltere system is weakly-coupled through mechanical linkages which synchronize phase and frequency. Wing-haltere link acts in a unidirectional manner; altering wingbeat frequency affects haltere frequency, but not vice-versa. Exoskeletal linkages are thus key morphological features of the Dipteran thorax which ensure wing-haltere synchrony, despite severe wing damage.

}, issn = {2050-084X}, doi = {10.7554/eLife.53824}, author = {Deora, Tanvi and Sane, Siddharth S and Sane, Sanjay P} } @article {79721, title = {A 2-Tyr-1-carboxylate Mononuclear Iron Center Forms the Active Site of a Paracoccus Dimethylformamidase.}, journal = {Angew Chem Int Ed Engl}, year = {2020}, month = {2020 May 25}, abstract = {

N,N-dimethyl formamide (DMF) is an extensively used organic solvent but is also a potent pollutant. Certain bacterial species from genera such as Paracoccus, Pseudomonas, and Alcaligenes have evolved to use DMF as a sole carbon and nitrogen source for growth via degradation by a dimethylformamidase (DMFase). We show that DMFase from Paracoccus sp. strain DMF is a halophilic and thermostable enzyme comprising a multimeric complex of the α β or (α β ) type. One of the three domains of the large subunit and the small subunit are hitherto undescribed protein folds of unknown evolutionary origin. The active site consists of a mononuclear iron coordinated by two Tyr side-chain phenolates and one carboxylate from Glu. The Fe ion in the active site catalyzes the hydrolytic cleavage of the amide bond in DMF. Kinetic characterization reveals that the enzyme shows cooperativity between subunits, and mutagenesis and structural data provide clues to the catalytic mechanism.

}, issn = {1521-3773}, doi = {10.1002/anie.202005332}, author = {Arya, Chetan Kumar and Yadav, Swati and Fine, Jonathan and Casanal, Ana and Chopra, Gaurav and Ramanathan, Gurunath and Vinothkumar, Kutti R and Subramanian, Ramaswamy} } @article {74446, title = {Adaptive evolution of honeybee dance dialects.}, journal = {Proc Biol Sci}, volume = {287}, year = {2020}, month = {2020 Mar 11}, pages = {20200190}, abstract = {

Efficient communication is highly important for the evolutionary success of social animals. Honeybees (genus ) are unique in that they communicate the spatial information of resources using a symbolic {\textquoteright}language{\textquoteright}, the waggle dance. Different honeybee species differ in foraging ecology but it remains unknown whether this shaped variation in the dance. We studied distance dialects-interspecific differences in how waggle duration relates to flight distance-and tested the hypothesis that these evolved to maximize communication precision over the bees{\textquoteright} foraging ranges. We performed feeder experiments with , and in India and found that had the steepest dialect, i.e. a rapid increase in waggle duration with increasing feeder distance, had an intermediate, and had the lowest dialect. By decoding dances for natural food sites, we inferred that the foraging range was smallest in , intermediate in and largest in . The inverse correlation between foraging range and dialect was corroborated when comparing six (sub)species across the geographical range of the genus including previously published data. We conclude that dance dialects constitute adaptations resulting from a trade-off between the spatial range and the spatial accuracy of communication.

}, issn = {1471-2954}, doi = {10.1098/rspb.2020.0190}, author = {Kohl, Patrick L and Thulasi, Neethu and Rutschmann, Benjamin and George, Ebi A and Steffan-Dewenter, Ingolf and Brockmann, Axel} } @article {79867, title = {Adaptive plasticity in wing melanisation of a montane butterfly across a Himalayan elevational gradient}, journal = {ECOLOGICAL ENTOMOLOGY}, year = {2020}, type = {07/2020}, abstract = {

Traits that are significant to the thermal ecology of temperate or montane species are expected to prominently co-vary with the thermal environment experienced by an organism. The HimalayanPieris canidiabutterfly exhibits considerable variation in wing melanisation. We investigated: (i) whether variation in wing melanisation and (ii) activity period of this montane butterfly was influenced by the seasonally and elevationally changing thermal landscape. We discovered that wing melanisation varied across elevation, seasons, sex, and wing surfaces, with the variation strongly structured in space and time: colder seasons and higher elevations produced more melanic individuals. Notably, melanisation did not vary uniformly across all wing surfaces: (i) melanisation of the ventral hindwing co-varied much more prominently with elevation, but (ii) melanisation on all other surfaces varied with seasonal changes in the thermal environment. Observed wing surface-specific patterns indicated thermoregulatory function for this variation in melanisation. Such wing surface-specific responses to seasonal and elevational variation in temperature have rarely been reported in montane insects. Moreover, daily and seasonal thermal cycles were found to strongly influence activity periods of this species, suggesting the potential limits to wing melanisation plasticity. Overall, these results showed that the seasonal and elevational gradients in temperature influence the thermal phenotype as well as activity periods of this Himalayan butterfly. It will be critical to study the phenotypic evolution of such montane insects in response to the ongoing climate change, which is already showing significant signs in this iconic mountain range.

}, doi = {10.1111/een.12911}, author = {Gautam, Shubham and Kunte, Krushnamegh} } @article {78111, title = {Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses.}, journal = {Aust N Z J Psychiatry}, year = {2020}, month = {2020 Jun 15}, pages = {4867420931157}, abstract = {

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study.

METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder ( = 61), obsessive-compulsive disorder ( = 58), schizophrenia ( = 52), substance dependence ( = 59) or co-occurring diagnoses ( = 38), while 241 were at-risk first-degree relatives who were either unaffected ( = 210) or had other depressive or anxiety disorders ( = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated.

RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder.

CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

}, issn = {1440-1614}, doi = {10.1177/0004867420931157}, author = {Someshwar, Amala and Holla, Bharath and Pansari Agarwal, Preeti and Thomas, Anza and Jose, Anand and Joseph, Boban and Raju, Birudu and Karle, Hariprasad and Muthukumaran, M and Kodancha, Prabhath G and Kumar, Pramod and Reddy, Preethi V and Kumar Nadella, Ravi and Naik, Sanjay T and Mitra, Sayantanava and Mallappagiri, Sreenivasulu and Sreeraj, Vanteemar S and Balachander, Srinivas and Ganesh, Suhas and Murthy, Pratima and Benegal, Vivek and Reddy, Janardhan Yc and Jain, Sanjeev and Mahadevan, Jayant and Viswanath, Biju} } @article {73042, title = {Amide temperature coefficients in characterizing the allosteric effects of ligand binding on local stability in proteins.}, journal = {Biochem Biophys Res Commun}, year = {2020}, month = {2020 Feb 04}, abstract = {

Proteins can stabilize upon binding a ligand. Due to allosteric effects, the changes in stability can occur at regions far from the protein:ligand interface. Efficient methods to measure the changes in local stability upon ligand binding will be useful to understand allostery and may be helpful in protein engineering. In this work, we suggest the measurement of backbone amide temperature coefficients to probe the effect of ligand binding on the local stability of β-sheet rich proteins. The method was applied for two protein:ligand complexes with different binding affinities. The protein includes a beta-sheet network connected by hydrogen bonds. The measured temperature coefficient data captured the stabilizing effect of ligand binding, which propagated across the beta-sheet network of the protein. Intriguingly, the impact on the local and global stability of the protein was proportional to the strength of protein:ligand interaction.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2020.01.144}, author = {Chatterjee, Kiran Sankar and Hembram, Dambarudhar Shiba Sankar and Das, Ranabir} } @article {80107, title = {Analyses of non-coding somatic drivers in 2,658~cancer whole genomes.}, journal = {Nature}, volume = {578}, year = {2020}, month = {2020 02}, pages = {102-111}, abstract = {

The discovery of drivers of cancer has traditionally focused on protein-coding genes. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658\ genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers, raise doubts about others and identify novel candidates, including point mutations in the 5{\textquoteright} region of TP53, in the 3{\textquoteright} untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although\ point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

}, keywords = {Databases, Genetic, DNA Breaks, Gene Expression Regulation, Neoplastic, Genome, Human, Genome-Wide Association Study, Humans, INDEL Mutation, Mutation, Neoplasms}, issn = {1476-4687}, doi = {10.1038/s41586-020-1965-x}, author = {Rheinbay, Esther and Nielsen, Morten Muhlig and Abascal, Federico and Wala, Jeremiah A and Shapira, Ofer and Tiao, Grace and Hornsh{\o}j, Henrik and Hess, Julian M and Juul, Randi Istrup and Lin, Ziao and Feuerbach, Lars and Sabarinathan, Radhakrishnan and Madsen, Tobias and Kim, Jaegil and Mularoni, Loris and Shuai, Shimin and Lanz{\'o}s, Andr{\'e}s and Herrmann, Carl and Maruvka, Yosef E and Shen, Ciyue and Amin, Samirkumar B and Bandopadhayay, Pratiti and Bertl, Johanna and Boroevich, Keith A and Busanovich, John and Carlevaro-Fita, Joana and Chakravarty, Dimple and Chan, Calvin Wing Yiu and Craft, David and Dhingra, Priyanka and Diamanti, Klev and Fonseca, Nuno A and Gonzalez-Perez, Abel and Guo, Qianyun and Hamilton, Mark P and Haradhvala, Nicholas J and Hong, Chen and Isaev, Keren and Johnson, Todd A and Juul, Malene and Kahles, Andre and Kahraman, Abdullah and Kim, Youngwook and Komorowski, Jan and Kumar, Kiran and Kumar, Sushant and Lee, Donghoon and Lehmann, Kjong-Van and Li, Yilong and Liu, Eric Minwei and Lochovsky, Lucas and Park, Keunchil and Pich, Oriol and Roberts, Nicola D and Saksena, Gordon and Schumacher, Steven E and Sidiropoulos, Nikos and Sieverling, Lina and Sinnott-Armstrong, Nasa and Stewart, Chip and Tamborero, David and Tubio, Jose M C and Umer, Husen M and Uusk{\"u}la-Reimand, Liis and Wadelius, Claes and Wadi, Lina and Yao, Xiaotong and Zhang, Cheng-Zhong and Zhang, Jing and Haber, James E and Hobolth, Asger and Imielinski, Marcin and Kellis, Manolis and Lawrence, Michael S and von Mering, Christian and Nakagawa, Hidewaki and Raphael, Benjamin J and Rubin, Mark A and Sander, Chris and Stein, Lincoln D and Stuart, Joshua M and Tsunoda, Tatsuhiko and Wheeler, David A and Johnson, Rory and Reimand, J{\"u}ri and Gerstein, Mark and Khurana, Ekta and Campbell, Peter J and Lopez-Bigas, Nuria and Weischenfeldt, Joachim and Beroukhim, Rameen and Martincorena, I{\~n}igo and Pedersen, Jakob Skou and Getz, Gad} } @article {74440, title = {Another new Cyrtodactylus (Squamata: Gekkonidae) from Guwahati, Assam, India}, journal = {ZOOTAXA}, volume = {4732}, year = {2020}, month = {02/2020}, pages = {375-392}, abstract = {

We describe a new species of Cyrtodactylus from Guwahati city in the state of Assam, India and provide additional data on the recently described Cyrtodactylus guwahatiensis. Cyrtodactylus urbanus sp. nov. falls in the newly defined khasiensis group within the Indo-Burma clade of Cyrtodactylus and is the poorly supported sister taxon to Cyrtodactylus khasiensis. The new species differs from other members of the khasiensis group in mitochondrial sequence data (12.5-17.1\% uncorrected pairwise ND2 sequence divergence) as well as aspects of morphology including the number and arrangement of precloacal pores in males, the number of mid-ventral scales and paravertebral tubercles, and colour pattern. This is the second Cyrtodactylus endemic to the Guwahati region, the fourth from Assam and the twelfth from Northeast India.

}, doi = {10.11646/zootaxa.4732.3.2}, author = {Purkayastha, Jayaditya and Das, Madhurima and Bohra, Sanath Chandra and Bauer, Aaron M and Agarwal, Ishan} } @article {82442, title = {Antipredatory Responses of Mosquito Pupae to Non-Lethal Predation Threat-Behavioral Plasticity Across Life-History Stages.}, journal = {Environ Entomol}, year = {2020}, month = {2020 Sep 04}, abstract = {

Antipredatory behavioral responses tend to be energetically expensive, and prey species thus need to resolve trade-offs between these behaviors and other activities such as foraging and mating. While these trade-offs have been well-studied across taxa, less is known about how costs and benefits vary in different life-history contexts, and associated consequences. To address this question, we compared responses of the yellow fever mosquito (Aedes aegypti [Diptera: Culicidae]) to predation threat from guppy (Poecilia reticulata [Cyprinodontiformes: Poeciliidae]) across two life-history stages-larvae (data from previous study) and pupae (from this study). Pupae are motile but do not feed and are comparable to larvae in terms of behavior. To understand how physiological costs affect the threat sensitivity of pupae, we used sex (with size as a covariate) as a proxy for stored energy reserves, and quantified movement and space use patterns of male (small-sized) and female (large-sized) pupae when exposed to predation threat. We found that pupae did not alter movement when exposed to predator cues but instead altered spatial use by spending more time at the bottom of the water column. We found no effect of pupa sex (or size) on the behavioral responses we measured. We conclude that pupa behavior, both antipredatory and otherwise, is primarily targeted at minimizing energy expenditure, as compared with larval behavior, which appears to balance energy expenditure between the opposing pressures of foraging and of avoiding predation. We suggest that antipredatory defenses in metamorphosing prey are modulated by varying energetic trade-offs associated with different life-history stages.

}, issn = {1938-2936}, doi = {10.1093/ee/nvaa101}, author = {Chandrasegaran, Karthikeyan and Sriramamurthy, Rasikapriyaa and Singh, Avehi and Ravichandran, Pooja and Quader, Suhel} } @article {78173, title = {Are shed hair genomes the most effective noninvasive resource for estimating relationships in the wild?}, journal = {Ecol Evol}, volume = {10}, year = {2020}, month = {05/2020}, pages = {4583-4594}, abstract = {

Knowledge of relationships in wild populations is critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, study genetic connectivity, study genotype-phenotype associations, trace individuals, or track wildlife trade, many identified individuals need to be genotyped at thousands of loci, mostly from noninvasive samples. This requires us to (a) identify the most common noninvasive sample available from identified individuals, (b) assess the ability to acquire genome-wide data from such samples, and (c) evaluate the quality of such genome-wide data, and its ability to reconstruct relationships between animals within a population.We followed identified individuals from a wild endangered tiger population and found that shed hair samples were the most common compared to scat samples, opportunistically found carcasses, and opportunistic invasive samples. We extracted DNA from these samples, prepared whole genome sequencing libraries, and sequenced genomes from these.Whole genome sequencing methods resulted in between 25\%-98\% of the genome sequenced for five such samples. Exploratory population genetic analyses revealed that these data were free of holistic biases and could recover expected population structure and relatedness. Mitochondrial genomes recovered matrilineages in accordance with long-term monitoring data. Even with just five samples, we were able to uncover the matrilineage for three individuals with unknown ancestry.In summary, we demonstrated that noninvasive shed hair samples yield adequate quality and quantity of DNA in conjunction with sensitive library preparation methods, and provide reliable data from hundreds of thousands of SNPs across the genome. This makes shed hair an ideal noninvasive resource for studying individual-based genetics of elusive endangered species in the wild.Knowledge of relationships in wild populations is critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, study genetic connectivity, study genotype-phenotype associations, trace individuals, or track wildlife trade, many identified individuals need to be genotyped at thousands of loci, mostly from noninvasive samples. This requires us to (a) identify the most common noninvasive sample available from identified individuals, (b) assess the ability to acquire genome-wide data from such samples, and (c) evaluate the quality of such genome-wide data, and its ability to reconstruct relationships between animals within a population.We followed identified individuals from a wild endangered tiger population and found that shed hair samples were the most common compared to scat samples, opportunistically found carcasses, and opportunistic invasive samples. We extracted DNA from these samples, prepared whole genome sequencing libraries, and sequenced genomes from these.Whole genome sequencing methods resulted in between 25\%-98\% of the genome sequenced for five such samples. Exploratory population genetic analyses revealed that these data were free of holistic biases and could recover expected population structure and relatedness. Mitochondrial genomes recovered matrilineages in accordance with long-term monitoring data. Even with just five samples, we were able to uncover the matrilineage for three individuals with unknown ancestry.In summary, we demonstrated that noninvasive shed hair samples yield adequate quality and quantity of DNA in conjunction with sensitive library preparation methods, and provide reliable data from hundreds of thousands of SNPs across the genome. This makes shed hair an ideal noninvasive resource for studying individual-based genetics of elusive endangered species in the wild.

}, doi = {10.1002/ece3.6157}, author = {Khan, A and Patel, K and Bhattacharjee, S and Sharma, S and Chugani, AN and Sivaraman, K and Hosawad, V and Sahu,YK and Reddy, GV and Ramakrishnan, U} } @article {79864, title = {Assessing the status of critically endangered Kondana soft-furred rat (Millardia kondana) using integrative taxonomy: combining evidence from morphological, molecular and environmental niche modeling}, journal = {MAMMALIA}, volume = {84}, year = {2020}, month = {07/2020}, pages = {392-406}, abstract = {

Kondana soft-furred rat is a critically endangered (CR) species, known from a single locality - Sinhgad in the northern Western Ghats, India. However, the taxonomic status of this species is uncertain due to its close resemblance to the widely distributed soft-furred field rat Millardia meltada, which has serious implications on the conservation status of Millardia kondana. In this study, we assessed the current taxonomic status of M. kondana through an integrative approach combining morphological, molecular and environmental niche modeling analyses. We collected morphological data from the specimens around Sinhgad as well as preserved specimens in the museum. Both morphological and two-dimensional (2D) morphometrical analyses showed a significant difference between M. kondana and M. meltada. Molecular phylogeny based on cytochrome b gene revealed a sister relationship between M. kondana and M. meltada, and both species form distinct well-supported monophyletic clades. Niche modeling also predicted niche segregation between the two species: M. kondana preferred areas with a high elevation and precipitation seasonality while M. meltada favored regions with a low elevation and precipitation. We confirmed that M. kondana is taxonomically distinct from M. meltada, and based on our estimates of its occurrence and occupancy, M. kondana continues to be treated as CR until further detailed investigations.

}, doi = {10.1515/mammalia-2019-0056}, author = {Bajaru, Sameer B and Lajmi, Aparna and Manakadan, Ranjit and Kulavmode, Amol R. and Ramakrishnan, Uma} } @article {78160, title = {Association of a begomovirus-satellite complex with yellow vein and leaf curl disease of hollyhock (Alcea rosea) in India.}, journal = {Arch Virol}, year = {2020}, month = {2020 Jun 18}, abstract = {

Geminiviruses cause considerable yield loss in several crop plants worldwide. In 2016, several hollyhock plants displaying yellow mosaic and leaf curling symptoms were noticed in a nursery of Jawaharlal Nehru University, New Delhi, India. Analysis of the collected samples indicated an association of monopartite and bipartite begomoviruses with satellites. Three begomoviruses (including a member of a new begomovirus species), two alphasatellites, and a betasatellite were isolated from yellow-mosaic-disease-affected plants. Similarly, a begomovirus, two alphasatellites, and a betasatellite were found to be associated with leaf curl disease of hollyhock. These begomoviruses and satellites were found to be recombinants. By harboring diverse begomoviruses and satellite DNAs, hollyhock may serve as a potential source of virus inoculum.

}, issn = {1432-8798}, doi = {10.1007/s00705-020-04696-2}, author = {Kumar, Manish and Vinoth Kumar, R and Chakraborty, Supriya} } @article {73034, title = {Association of With the Apical Domain of Hepatocytes Is Necessary for the Parasite{\textquoteright}s Liver Stage Development.}, journal = {Front Cell Infect Microbiol}, volume = {9}, year = {2020}, month = {2019}, pages = {451}, abstract = {

parasites undergo a dramatic transformation during the liver stage of their life cycle, amplifying over 10,000-fold inside infected hepatocytes within a few days. Such a rapid growth requires large-scale interactions with, and manipulations of, host cell functions. Whereas hepatocyte polarity is well-known to be critical for liver function, little is presently known about its involvement during the liver stage of development. Apical domains of hepatocytes are critical components of their polarity machinery and constitute the bile canalicular network, which is central to liver function. Here, we employed high resolution 3-D imaging and advanced image analysis of -infected liver tissues to show that the parasite associates preferentially with the apical domain of hepatocytes and induces alterations in the organization of these regions, resulting in localized changes in the bile canalicular architecture in the liver tissue. Pharmacological perturbation of the bile canalicular network by modulation of AMPK activity reduces the parasite{\textquoteright}s association with bile canaliculi and arrests the parasite development. Our findings using -infected liver tissues reveal a host- interaction at the level of liver tissue organization. We demonstrate for the first time a role for bile canaliculi, a central component of the hepatocyte polarity machinery, during the liver stage of development.

}, issn = {2235-2988}, doi = {10.3389/fcimb.2019.00451}, author = {Balasubramanian, Lakshmi and Zuzarte-Lu{\'\i}s, Vanessa and Syed, Tabish and Mullick, Debakshi and Deb, Saptarathi and Ranga-Prasad, Harish and Meissner, Jana and Almeida, Ana and Furstenhaupt, Tobias and Siddiqi, Kaleem and Prud{\^e}ncio, Miguel and Rodrigues, Cecilia M P and Mota, Maria and Sundaramurthy, Varadharajan} } @article {84575, title = {Asymmetric chromosome segregation and cell division in DNA damage-induced bacterial filaments.}, journal = {Mol Biol Cell}, volume = {31}, year = {2020}, month = {12/2020}, pages = {2920-2931}, abstract = {

Faithful propagation of life requires coordination of DNA replication and segregation with cell growth and division. In bacteria, this results in cell size homeostasis and periodicity in replication and division. The situation is perturbed under stress such as DNA damage, which induces filamentation as cell cycle progression is blocked to allow for repair. Mechanisms that release this morphological state for re-entry into wild type growth are unclear. Here we show that damage-induced filaments divide asymmetrically, producing short daughter cells that tend to be devoid of damage and have wild type size and growth dynamics. The Min system primarily determines division site location in the filament, with additional regulation of division completion by chromosome segregation. Collectively, we propose that coordination between chromosome (and specifically segregation and cell division may result in asymmetric division in damage-induced filaments and facilitate recovery from a stressed state.

}, issn = {1939-4586}, doi = {10.1091/mbc.E20-08-0547}, author = {Raghunathan, Suchitha and Chimthanawala, Afroze and Krishna, Sandeep and Vecchiarelli, Anthony G and Badrinarayanan, Anjana} } @article {80781, title = {The bacterial quorum sensing signal DSF hijacks sterol biosynthesis to suppress plant innate immunity.}, journal = {Life Sci Alliance}, volume = {3}, year = {2020}, month = {2020 Oct}, abstract = {

Quorum sensing (QS) is a recognized phenomenon that is crucial for regulating population-related behaviors in bacteria. However, the direct specific effect of QS molecules on host biology is largely understudied. In this work, we show that the QS molecule DSF (-11-methyl-dodecenoic acid) produced by pv. can suppress pathogen-associated molecular pattern-triggered immunity (PTI) in , mediated by flagellin-induced activation of flagellin receptor FLS2. The DSF-mediated attenuation of innate immunity results from the alteration of FLS2 nanoclusters and endocytic internalization of plasma membrane FLS2. DSF altered the lipid profile of , with a particular increase in the phytosterol species, which impairs the general endocytosis pathway mediated by clathrin and FLS2 nano-clustering on the plasma membrane. The DSF effect on receptor dynamics and host immune responses could be entirely reversed by sterol removal. Together, our results highlighted the importance of sterol homeostasis to plasma membrane organization and demonstrate a novel mechanism by which pathogenic bacteria use their communicating molecule to manipulate pathogen-associated molecular pattern-triggered host immunity.

}, issn = {2575-1077}, doi = {10.26508/lsa.202000720}, author = {Tran, Tuan Minh and Ma, Zhiming and Triebl, Alexander and Nath, Sangeeta and Cheng, Yingying and Gong, Ben-Qiang and Han, Xiao and Wang, Junqi and Li, Jian-Feng and Wenk, Markus R and Torta, Federico and Mayor, Satyajit and Yang, Liang and Miao, Yansong} } @article {86516, title = {Baffling: a condition-dependent alternative mate attraction strategy using self-made tools in tree crickets.}, journal = {Proc Biol Sci}, volume = {287}, year = {2020}, month = {2020 Dec 23}, pages = {20202229}, abstract = {

Intense sexual selection in the form of mate choice can facilitate the evolution of different alternative reproductive strategies, which can be condition-dependent. Tree cricket males produce long-distance acoustic signals which are used by conspecific females for mate localization and mate choice. Our study shows that baffling, an acoustic call amplification strategy employed by male tree crickets using self-made tools, is a classic example of a condition-dependent alternative strategy. We show that though most males can baffle, less preferred males, such as smaller and lower-amplitude callers, predominantly use this alternative strategy. Baffling allows these males to increase their call amplitude and advertisement range, which attracts a higher number of females. Baffling also gives these males a mating benefit because females mate for longer durations with them. Our results suggest that the advantage of baffling in terms of gain in the number of sperm cells transferred while mating is primarily limited to less preferred males, thus maintaining the polymorphism of calling strategies in the population. We summarize that baffling is a condition-dependent strategy used by less preferred tree cricket males to obtain mating benefits.

}, issn = {1471-2954}, doi = {10.1098/rspb.2020.2229}, author = {Deb, Rittik and Modak, Sambita and Balakrishnan, Rohini} } @article {78108, title = {Beyond the coding genome: non-coding mutations and cancer.}, journal = {Front Biosci (Landmark Ed)}, volume = {25}, year = {2020}, month = {2020 Jun 01}, pages = {1828-1838}, abstract = {

Latest advancements in genomics involving individuals from different races and geographical locations has led to the identification of thousands of common as well as rare genetic variants and copy number variations (CNVs). These studies have surprisingly revealed that the majority of genetic variation is not present within the coding region but rather in the non-coding region of the genome, which is also termed as "Medical Genome". This short review describes how mutations/variations within; regulatory sequences, architectural proteins and transcriptional regulators give rise to the aberrant gene expression profiles that drives cellular transformations and malignancies.

}, issn = {1093-4715}, author = {Walavalkar, Kaivalya and Notani, Dimple} } @article {87088, title = {Brain circuits at risk in psychiatric diseases and pharmacological pathways.}, journal = {Therapie}, volume = {S0040-5957}, year = {2020}, month = {12/2020}, pages = {30222-5}, abstract = {

The multiple brain circuits involved in psychiatric diseases may appear daunting, but we prefer to concentrate on a select few, with a particular sensitivity to stress and neurodevelopmental issues, with a clear pharmacotherapy. This review is structured around 1. the key circuits, their role in health and disease, and the neurotransmitters maintaining them, 2. The influence of upbringing, stress, chronobiology, inflammation and infection, 3. The genetic and epigenetic influence on these circuits, particularly regarding copy number variants and neuronal plasticity, 4. The use and abuse of pharmacological agents with the particular risks of stress and chronobiology at critical periods. A major emphasis is placed on the links between hippocampus, prefrontal cortex and amygdala/periaqueductal grey which control specific aspects of cognition, mood, pain and even violence. Some of the research findings were from the innovative medicine initiative (IMI) NEWMEDS, a 22M{\texteuro} academic/industrial consortium on the brain circuits critical for psychiatric disease.

}, doi = {10.1016/j.therap.2020.12.005}, author = {Spedding, M and Chattarji, S and Spedding, C and Jay, TM} } @article {87674, title = {Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.}, journal = {Commun Biol}, volume = {3}, year = {2020}, month = {2020 02 05}, pages = {56}, abstract = {

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.

}, issn = {2399-3642}, doi = {10.1038/s42003-019-0741-7}, author = {Carlevaro-Fita, Joana and Lanz{\'o}s, Andr{\'e}s and Feuerbach, Lars and Hong, Chen and Mas-Ponte, David and Pedersen, Jakob Skou and Johnson, Rory} } @article {80778, title = {Caspar SUMOylation regulates lifespan.}, journal = {MicroPubl Biol}, volume = {2020}, year = {2020}, month = {2020 Aug 02}, issn = {2578-9430}, doi = {10.17912/micropub.biology.000288}, author = {Kaduskar, Bhagyashree and Trivedi, Deepti and Ratnaparkhi, Girish S} } @article {72068, title = {Cetacean Distribution and Diversity in Lakshadweep Waters, India, Using a Platform of Opportunity: October 2015 to April 2016}, journal = {AQUATIC MAMMALS}, volume = {46}, year = {2020}, month = {01/2020}, pages = {80-92}, abstract = {

Prior stranding records suggest that at least 12 cetacean species occur within the Lakshadweep archipelago off the southwest coast of India. These islands consist of coral atolls and form the northern part of the undersea Chagos-Laccadive ridge. Distinct oceanographic features, seasonal monsoon cycles, and high productivity make this region a potentially rich cetacean habitat. In this article, we report findings from the first systematic visual cetacean surveys, which were conducted from high-speed passenger ferries that sail between nine Lakshadweep islands. The surveys were carried out between October 2015 and April 2016 during both the northeast monsoon (October to December) and inter-monsoon (January to April) seasons. We used a line-transect survey framework to record sightings as well as group size estimates. We documented 139 sightings over 3,880 km of which 78 sightings were during systematic survey effort. Eight odontocete species were confirmed from these sightings: Stenella longirostris, S. attenuata, S. coeruleoalba, Tursiops spp., Globicephala macrorhynchus, Pseudorca crassidens, Grampus griseus, and Feresa attenuata. One Balaenoptera sp. was also encountered during this survey. S. longirostris was sighted the most often (n = 22) followed by Tursiops spp. (n = 18) and G. macrorhynchus (n = 13). We documented significantly higher sightings in the northeast monsoon season compared to the inter-monsoon season. Along ferry routes, cetacean species differed significantly from each other with respect to their associations with seafloor slope gradients and distances to nearest landmass. We encountered mixed species assemblages of G. macrorhynchus with Tursiops sp. and S. attenuata with Tursiops sp. Given the confirmed high cetacean diversity and occurrence in this region, there is a need for in-depth, long-term studies on biogeography, ecology, and population status of cetaceans here.

}, doi = {10.1578/AM.46.1.2020.80}, author = {Panicker, Divya and Sutaria, Dipani and Kumar, Ajith and Stafford, Kathleen M} } @article {82954, title = {Changing ecologies, shifting behaviours: Behavioural responses of a rainforest primate, the lion-tailed macaque Macaca silenus, to a matrix of anthropogenic habitats in southern India.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0238695}, abstract = {

With the uncontrolled expansion of anthropogenic modifications of the environment, wildlife species are forced to interact with humans, often leading to conflict situations that have detrimental effects for both wildlife and humans. Such interactions are escalating globally, making it crucial for us to devise strategies for both, the management of conflict and the conservation of these often-threatened species. We studied a case of potentially detrimental human-wildlife interactions between an endemic, habitat-specialist primate, the lion-tailed macaque Macaca silenus and resident human communities that has developed in recent years in the Western Ghats mountains of southern India. Primates provide useful model systems to understand the extent and nature of behavioural changes exhibited by wildlife in response to anthropogenic habitats with varying degrees of human influence. We documented behaviours, including foraging and intra-species social interactions, to examine the decisions made by the macaques as they exploited four human-modified habitats, which, for the purpose of this study, have been qualitatively characterised to include structural features of the habitat, type of food resources available and the presence of humans. Access to human-origin food, either cooked or packaged, acquired directly from homes or garbage pits, in the human-dominated habitat appeared to significantly reduce active foraging and searching for food, allowing them to engage in other behavioural activities, such as resting. Furthermore, patterns of reciprocated affiliation dissipated in certain human-dominated habitats, with individuals seeming to have adopted novel behavioural strategies, leading to altered social dynamics in the troop, possibly in response to provisioning. This study thus highlights the importance of understanding behavioural changes displayed by animals in response to human interactions; such knowledge could be crucial for the planning and implementation of management and conservation strategies for endangered species such as the lion-tailed macaque and possibly other wildlife in the increasingly anthropogenic landscapes of the tropical world.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0238695}, author = {Dhawale, Ashni Kumar and Kumar, M Ananda and Sinha, Anindya} } @article {78003, title = {Characterizing long-range search behavior in Diptera using complex 3D virtual environments.}, journal = {Proc Natl Acad Sci U S A}, volume = {117}, year = {2020}, month = {2020 Jun 02}, pages = {12201-12207}, abstract = {

The exemplary search capabilities of flying insects have established them as one of the most diverse taxa on Earth. However, we still lack the fundamental ability to quantify, represent, and predict trajectories under natural contexts to understand search and its applications. For example, flying insects have evolved in complex multimodal three-dimensional (3D) environments, but we do not yet understand which features of the natural world are used to locate distant objects. Here, we independently and dynamically manipulate 3D objects, airflow fields, and odor plumes in virtual reality over large spatial and temporal scales. We demonstrate that flies make use of features such as foreground segmentation, perspective, motion parallax, and integration of multiple modalities to navigate to objects in a complex 3D landscape while in flight. We first show that tethered flying insects of multiple species navigate to virtual 3D objects. Using the apple fly , we then measure their reactive distance to objects and show that these flies use perspective and local parallax cues to distinguish and navigate to virtual objects of different sizes and distances. We also show that apple flies can orient in the absence of optic flow by using only directional airflow cues, and require simultaneous odor and directional airflow input for plume following to a host volatile blend. The elucidation of these features unlocks the opportunity to quantify parameters underlying insect behavior such as reactive space, optimal foraging, and dispersal, as well as develop strategies for pest management, pollination, robotics, and search algorithms.

}, issn = {1091-6490}, doi = {10.1073/pnas.1912124117}, author = {Kaushik, Pavan Kumar and Renz, Marian and Olsson, Shannon B} } @article {87964, title = {Circadian clock effects on cellular proliferation: Insights from theory and experiments.}, journal = {Curr Opin Cell Biol}, volume = {67}, year = {2020}, month = {2020 Dec}, pages = {17-26}, abstract = {

Oscillations of the cellular circadian clock have emerged as an important regulator of many physiological processes, both in health and in disease. One such process, cellular proliferation, is being increasingly recognized to be affected by the circadian clock. Here, we review how a combination of experimental and theoretical work has furthered our understanding of the way circadian clocks couple to the cell cycle and play a role in tissue homeostasis and cancer. Finally, we discuss recently introduced methods for modeling coupling of clocks based on techniques from survival analysis and machine learning and highlight their potential importance for future studies.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2020.07.003}, author = {Chakrabarti, Shaon and Michor, Franziska} } @article {84578, title = {Closely related species show species-specific environmental responses and different spatial conservation needs: Prionailurus cats in the Indian subcontinent.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {2020 Oct 30}, pages = {18705}, abstract = {

Phylogenetically closely related species are often assumed to have similar responses to environmental conditions, but species-specific responses have also been described. These two scenarios may have different conservation implications. We tested these two hypotheses for Prionailurus cats (P. rubiginosus, P. bengalensis, P. viverrinus) in the Indian subcontinent and show its implications on species current protected area coverage and climatic suitability trends through time. We fitted ecological niche models with current environmental conditions and calculated niche overlap. In addition, we developed a model for the Jungle Cat Felis chaus to compare species responses and niche overlap estimates within Prionailurus with those for a related sympatric small cat species. Then we estimated the proportion of current suitable environment covered by protected area and projected climatic models from past (last interglacial) to future (2070; RCP4.5 and RCP8.5) conditions to show implications on population management and conservation. The hypothesis of a similar response and niche overlap among closely related species is not supported. Protected area coverage was lowest for P. viverrinus (mean = 0.071, SD = 0.012) and highest for P. bengalensis (mean = 0.088, SD = 0.006). In addition, the proportion of the subcontinent with suitable climate varied through time and was species-specific. For P. bengalensis, climatic suitability shrunk since at least the mid-Holocene, a trend that can be intensified by human-induced climate warming. Concerning P. viverrinus, most predictions show stable future climatic suitability, but a few indicated potential loss. Climatic suitability for P. rubiginous was predicted to remain stable but the species exhibited a negative association with intensive agriculture. Similar responses to environmental change by phylogenetically closely related species should not be assumed and have implications on protected area coverage and natural trends of species climatic suitability over time. This should be taken into account during conservation and management actions.

}, issn = {2045-2322}, doi = {10.1038/s41598-020-74684-8}, author = {Silva, Andr{\'e} P and Mukherjee, Shomita and Ramakrishnan, Uma and Fernandes, Carlos and Bj{\"o}rklund, Mats} } @article {73645, title = {A coherent feed forward loop drives vascular regeneration in damaged aerial organs growing in normal developmental-context.}, journal = {Development}, year = {2020}, month = {2020 Feb 27}, abstract = {

Aerial organs of plants being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaf and stem to study the reunion between mechanically disconnected tissues. We show that ()/ () genes, which encodes stem cell promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. Both PLT and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT mediated regeneration response, leaf ground tissue cells can neither acquire early vascular identity marker ATHB8, nor properly polarize auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaf. We reveal the mechanisms of vascular regeneration in plants and distinguishes the wound repair ability of the tissue from its formation during normal development.

}, issn = {1477-9129}, doi = {10.1242/dev.185710}, author = {Radhakrishnan, Dhanya and Shanmukhan, Anju Pallipurath and Kareem, Abdul and Aiyaz, Mohammed and Varapparambathu, Vijina and Toms, Ashna and Kerstens, Merijn and Valsakumar, Devisree and Landge, Amit N and Shaji, Anil and Mathew, M K and Sawchuk, Megan G and Scarpella, Enrico and Krizek, Beth A and Efroni, Idan and M{\"a}h{\"o}nen, Ari Pekka and Willemsen, Viola and Scheres, Ben and Prasad, Kalika} } @article {80091, title = {Comparison of CryoEM and X-ray structures of dimethylformamidase.}, journal = {Prog Biophys Mol Biol}, year = {2020}, month = {2020 Jul 28}, abstract = {

Dimethylformamidase (DMFase) catalyzes the hydrolysis of dimethylformamide, an industrial solvent, introduced into the environment by humans. Recently, we determined the structures of dimethylformamidase by electron cryo microscopy and X-ray crystallography revealing a tetrameric enzyme with a mononuclear iron at the active site. DMFase from Paracoccus sp. isolated from a waste water treatment plant around the city of Kanpur in India shows maximal activity at 54 {\textdegree}C and is halotolerant. The structures determined by both techniques are mostly identical and the largest difference is in a loop near the active site. This loop could play a role in co-operativity between the monomers. A number of non-protein densities are observed in the EM map, which are modelled as water molecules. Comparison of the structures determined by the two methods reveals conserved water molecules that could play a structural role. The higher stability, unusual active site and negligible activity at low temperature makes this a very good model to study enzyme mechanism by cryoEM.

}, issn = {1873-1732}, doi = {10.1016/j.pbiomolbio.2020.06.008}, author = {Vinothkumar, Kutti R and Arya, Chetan and Ramanathan, Gurunath and Subramanian, Ramaswamy} } @article {79804, title = {Computational search for potential COVID-19 drugs from FDAapproved drugs and small molecules of natural origin identifies several anti-virals and plant products.}, journal = {J Biosci}, volume = {45}, year = {2020}, month = {2020}, abstract = {

The world is currently facing the COVID-19 pandemic, for which mild symptoms include fever and dry cough. In severe cases, it could lead to pneumonia and ultimately death in some instances. Moreover, the causative pathogen is highly contagious and there are no drugs or vaccines for it yet. The pathogen, SARS-CoV-2, is one of the human coronaviruses which was identified to infect humans first in December 2019. SARS-CoV-2 shares evolutionary relationship to other highly pathogenic viruses such as Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS). We have exploited this similarity to model a target non-structural protein, NSP1, since it is implicated in the regulation of host gene expression by the virus and hijacking of host machinery. We next interrogated the capacity to repurpose around 2300 FDA-approved drugs and more than 3,00,000 small molecules of natural origin towards drug identification through virtual screening and molecular dynamics. Interestingly, we observed simple molecules like lactose, previously known anti-virals and few secondary metabolites of plants as promising hits. These herbal plants are already practiced in Ayurveda over centuries to treat respiratory problems and inflammation. Disclaimer: we would not like to recommend uptake of these small molecules for suspect COVID patients until it is approved by competent national or international authorities.

}, issn = {0973-7138}, author = {Sharma, Abhishek and Tiwari, Vikas and Sowdhamini, Ramanathan} } @article {73044, title = {Cone snail analogs of the pituitary hormones oxytocin/vasopressin and their carrier protein neurophysin. Proteomic and transcriptomic identification of conopressins and conophysins.}, journal = {Biochim Biophys Acta Proteins Proteom}, year = {2020}, month = {2020 Feb 10}, pages = {140391}, abstract = {

Transcriptomic analysis of cone snail venom duct tissue has permitted the identification of diverse conopressin/conophysin precursor sequences from seven distinct conus species. Multiple precursor isoforms are present in C.monile, C.lividus and C.loroisii. Aqueous extracts of the venom duct tissue from C.monile yield a band, at ~ 15-20 kDa on SDS-PAGE. In-gel trypsin digestion, followed by mass spectrometry establishes the presence of two distinct conopressin/conophysin isoforms that differ at position 8 in the predicted conopressin nonapeptide sequence. Mass spectrometric analysis of aqueous extracts revealed the presence of four conopressin related peptides, whose sequences could be deduced from MS/MS fragmentation patterns. The four sequences determined in this study are CFIRNCPKG*, CFIRNCPEG*, CFIRNCPK* and CFIRNCPE* (* indicates amide), which were further confirmed by comparison with chemically synthesized peptides. A conophysin with a mass of 9419.7 Da was also detected, corresponding to one of the isoforms revealed by the transcriptome data. Complete conservation of fourteen Cys residues and the key residues involved in peptide hormone binding is established by comparison of conophysin sequences, with the crystallographically characterized sequence of bovine neurophysin, in complex with vasopressin. A survey of available sequences for oxytocin/vasopressin peptides in both vertebrates and invertebrates establishes the conopressins as a distinct group in this family. C-terminal amidated, truncated conopressin analogs may arise by alternate post-translational processing.

}, issn = {1878-1454}, doi = {10.1016/j.bbapap.2020.140391}, author = {Kumar, Sanjeev and Vijayasarathy, M and Venkatesha, M A and Sunita, P and Balaram, P} } @article {85182, title = {Conservation status of the dhole Cuon alpinus in north-east India, with a focus on Dampa Tiger Reserve, Mizoram}, journal = {ORYX}, volume = {54}, year = {2020}, month = {11/2020}, pages = {873-877}, abstract = {

Despite the efforts invested in their conservation, the status of many threatened carnivores in key conservation landscapes remains unknown. The dhole Cuon alpinus is an Endangered social carnivore whose geographical range has contracted by c. 80\% since the early 20th century. North-east India is a critical link between South Asian and South-east Asian dhole populations. In this study we compiled presence records of dholes across north-east India, from multiple sources. We also conducted camera-trap surveys in one part of this region, Dampa Tiger Reserve in the state of Mizoram. We examined the influence of ecological and management factors on fine-scale site-use by dholes in Dampa Tiger Reserve, showing a positive association of dhole site-use with sambar Rusa unicolor encounters, distance to the forest boundary and presence of forest department personnel, underscoring the importance of prey and protection. Our findings also highlight the need for targeted, multi-scale assessments of dhole ecology across other sites in north-east India.

}, doi = {10.1017/S0030605319000255}, author = {Singh, Priya and Srivathsa, Arjun and Macdonald, David W.} } @article {73040, title = {A conserved sequence signature is essential for robust plant miRNA biogenesis.}, journal = {Nucleic Acids Res}, year = {2020}, month = {2020 Feb 06}, abstract = {

Micro (mi)RNAs are 20-22nt long non-coding RNA molecules involved in post-transcriptional silencing of targets having high base-pair complementarity. Plant miRNAs are processed from long Pol II-transcripts with specific stem-loop structures by Dicer-like (DCL) 1 protein. Although there were reports indicating how a specific region is selected for miRNA biogenesis, molecular details were unclear. Here, we show that the presence of specific GC-rich sequence signature within miRNA/miRNA* region is required for the precise miRNA biogenesis. The involvement of GC-rich signatures in precise processing and abundance of miRNAs was confirmed through detailed molecular and functional analysis. Consistent with the presence of the miRNA-specific GC signature, target RNAs of miRNAs also possess conserved complementary sequence signatures in their miRNA binding motifs. The selection of these GC signatures was dependent on an RNA binding protein partner of DCL1 named HYL1. Finally, we demonstrate a direct application of this discovery for enhancing the abundance and efficiency of artificial miRNAs that are popular in plant functional genomic studies.

}, issn = {1362-4962}, doi = {10.1093/nar/gkaa077}, author = {Narjala, Anushree and Nair, Ashwin and Tirumalai, Varsha and G Vivek Hari Sundar and Shivaprasad, Padubidri V} } @article {77438, title = {Convolvulus pluricaulis extract can modulate synaptic plasticity in rat brain hippocampus.}, journal = {Neuroreport}, volume = {31}, year = {2020}, month = {2020 May 22}, pages = {597-604}, abstract = {

The memory-boosting property of Indian traditional herb, Convolvulus pluricaulis, has been documented in literature; however, its effect on synaptic plasticity has not yet been reported. Two important forms of synaptic plasticity known to be involved in the processes of memory formation are long-term potentiation (LTP) and long-term depression (LTD). In the present study, the effect of C. pluricaulis plant extract on LTP and LTD were evaluated. The adult male Wistar rats were fed orally with 250, 500 and 1000 mg/kg of this extract for 4 weeks and the effect was determined on LTP and LTD in the Schaffer collaterals of the hippocampal cornu ammonis region CA1. We found that the 500 mg/kg dose of the extract could significantly enhance LTP compared to the vehicle treated ones. Moreover, the same dose could also reduce LTD while used in a separate set of animals. Also, a fresh group of animals treated with the effective dose (500 mg/kg) of plant extract were examined for memory retention in two behavioral platforms namely, contextual fear conditioning (CFC) and novel object recognition test (NORT). Increased fear response to the conditioned stimulus and enhanced recognition of objects were observed in CFC and NORT, respectively, both indicating strengthening of memory. Following up, ex-vivo electrophysiology experiments were performed with the active single molecule scopoletin, present in C. pluricaulis extract and similar patterns in synaptic plasticity changes were obtained. These findings suggest that prolonged treatment of C. pluricaulis extract, at a specific dose in healthy animals, can augment memory functions by modulating hippocampal plasticity.

}, issn = {1473-558X}, doi = {10.1097/WNR.0000000000001446}, author = {Das, Rishi and Sengupta, Tathagata and Roy, Shubhrajit and Chattarji, Sumantra and Ray, Jharna} } @article {78161, title = {Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns.}, journal = {Mol Autism}, volume = {11}, year = {2020}, month = {2020 Jun 19}, pages = {52}, abstract = {

BACKGROUND: Fragile X syndrome (FXS), a neurodevelopmental disorder, is a leading monogenetic cause of intellectual disability and autism spectrum disorder. Notwithstanding the extensive studies using rodent and other pre-clinical models of FXS, which have provided detailed mechanistic insights into the pathophysiology of this disorder, it is only relatively recently that human stem cell-derived neurons have been employed as a model system to further our understanding of the pathophysiological events that may underlie FXS. Our study assesses the physiological properties of human pluripotent stem cell-derived cortical neurons lacking fragile X mental retardation protein (FMRP).

METHODS: Electrophysiological whole-cell voltage- and current-clamp recordings were performed on two control and three FXS patient lines of human cortical neurons derived from induced pluripotent stem cells. In addition, we also describe the properties of an isogenic pair of lines in one of which FMR1 gene expression has been silenced.

RESULTS: Neurons lacking FMRP displayed bursts of spontaneous action potential firing that were more frequent but shorter in duration compared to those recorded from neurons expressing FMRP. Inhibition of large conductance Ca-activated K currents and the persistent Na current in control neurons phenocopies action potential bursting observed in neurons lacking FMRP, while in neurons lacking FMRP pharmacological potentiation of voltage-dependent Na channels phenocopies action potential bursting observed in control neurons. Notwithstanding the changes in spontaneous action potential firing, we did not observe any differences in the intrinsic properties of neurons in any of the lines examined. Moreover, we did not detect any differences in the properties of miniature excitatory postsynaptic currents in any of the lines.

CONCLUSIONS: Pharmacological manipulations can alter the action potential burst profiles in both control and FMRP-null human cortical neurons, making them appear like their genetic counterpart. Our studies indicate that FMRP targets that have been found in rodent models of FXS are also potential targets in a human-based model system, and we suggest potential mechanisms by which activity is altered.

}, issn = {2040-2392}, doi = {10.1186/s13229-020-00351-4}, author = {Das Sharma, Shreya and Pal, Rakhi and Reddy, Bharath Kumar and Selvaraj, Bhuvaneish T and Raj, Nisha and Samaga, Krishna Kumar and Srinivasan, Durga J and Ornelas, Loren and Sareen, Dhruv and Livesey, Matthew R and Bassell, Gary J and Svendsen, Clive N and Kind, Peter C and Chandran, Siddharthan and Chattarji, Sumantra and Wyllie, David J A} } @article {79718, title = {Corticosterone after acute stress prevents the delayed effects on the amygdala.}, journal = {Neuropsychopharmacology}, year = {2020}, month = {2020 Jul 06}, abstract = {

Even a single 2-hour episode of immobilization stress is known to trigger anxiety-like behavior and increase spine-density in the basolateral amygdala (BLA) of rats 10 days later. This delayed build-up of morphological and behavioral effects offers a stress-free time window of intervention after acute stress, which we used to test a protective role for glucocorticoids against stress. We observed that post-stress corticosterone, given 1 day after acute stress in drinking water, reversed enhanced anxiety-like behavior 10 days later. Quantification of spine-density on Golgi-stained BLA principal neurons showed that the same intervention also prevented the increase in spine numbers in the amygdala, at the same delayed time-point. Further, stress elevated serum corticosterone levels in rats that received vehicle in the drinking water. However, when stress was followed 24 h later by corticosterone in the drinking water, the surge in corticosterone was prevented. Together, these observations suggest that corticosterone, delivered through drinking water even 24 h after acute stress, is capable of reversing the delayed enhancing effects on BLA synaptic connectivity and anxiety-like behavior. Strikingly, although the immobilization-induced surge in corticosterone by itself has delayed detrimental effects on amygdalar structure and function, there exists a window of opportunity even after stress to mitigate its impact with a second surge of exogenously administered corticosterone. This provides a framework in the amygdala for analyzing how the initial physiological and endocrine processes triggered by traumatic stress eventually give rise to debilitating emotional symptoms, as well as the protective effects of glucocorticoids against their development.

}, issn = {1740-634X}, doi = {10.1038/s41386-020-0758-0}, author = {Chakraborty, Prabahan and Datta, Siddhartha and McEwen, Bruce S and Chattarji, Sumantra} } @article {77376, title = {Could drought constrain woody encroachers in savannas?}, journal = {AFRICAN JOURNAL OF RANGE \& FORAGE SCIENCE}, volume = {37}, year = {2020}, month = {01/2020}, pages = {19-29}, abstract = {

Droughts are expected to become more frequent and severe, due to climate change, with uncertain consequences for savanna vegetation. Drought-driven tree mortality has been observed in some savannas, but little is known about how tolerant savanna trees are to drought, or what determines differences among species in drought vulnerability. Here, we examine which characteristics best distinguished tree species that were most negatively affected by a recent drought in Kruger National Park, South Africa. Woody-encroaching, root-suckering species, which tended to have relatively low investments in non-structural carbohydrates, had the highest mortality rates. Of particular interest was Dichrostachys cinerea, a notable contributor to widespread woody encroachment across southern African savannas, which suffered high drought mortality. Using rainfall maps and vegetation survey data, we show that D. cinerea distributions in Kruger National Park are limited to areas with higher mean annual rainfall and lower past drought frequency, and stem densities are lower where droughts have occurred more frequently, suggesting that past droughts have had lasting impacts on the distribution and abundance of this species. Woody encroachers, such as D. cinerea, may face a trade off between traits promoting proliferation vs. drought tolerance, and more frequent and severe droughts could increasingly limit their spread.

}, doi = {10.2989/10220119.2019.1697363}, author = {Case, MF and Wigley, BJ and Wigley-Coetsee, C and Staver, AC} } @article {78096, title = {Dataset for the combined transcriptome assembly of and functional annotation.}, journal = {Data Brief}, volume = {30}, year = {2020}, month = {2020 Jun}, pages = {105416}, abstract = {

In this paper, we present the data acquired during transcriptome analysis of the Moringa oleifera [1] from five different tissues (root, stem, leaf, flower and seed) by RNA sequencing. A total of 271 million reads were assembled with an N50 of 2094 bp. The combined transcriptome was assessed for transcript abundance across five tissues. The protein coding genes identified from the transcripts were annotated and used for orthology analysis. Further, enzymes involved in the biosynthesis of select medicinally important secondary metabolites, vitamins and ion transporters were identified and their expression levels across tissues were examined. The data generated by RNA sequencing has been deposited to NCBI public repository under the accession number PRJNA394193 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA394193).

}, issn = {2352-3409}, doi = {10.1016/j.dib.2020.105416}, author = {Shafi, K Mohamed and Joshi, Adwait G and Meenakshi, Iyer and Pasha, Shaik Naseer and Harini, K and Mahita, Jarjapu and Sajeevan, Radha Sivarajan and Karpe, Snehal D and Ghosh, Pritha and Nitish, Sathyanarayanan and Gandhimathi, A and Mathew, Oommen K and Prasanna, Subramanian Hari and Malini, Manoharan and Mutt, Eshita and Naika, Mahantesha and Ravooru, Nithin and Rao, Rajas M and Shingate, Prashant N and Sukhwal, Anshul and Sunitha, Margaret S and Upadhyay, Atul K and Vinekar, Rithvik S and Sowdhamini, Ramanathan} } @article {83749, title = {Defence versus growth in a hostile world: lessons from phage and bacteria.}, journal = {R Soc Open Sci}, volume = {7}, year = {2020}, month = {2020 Sep}, pages = {201118}, abstract = {

Bacterial communities are often highly diverse with several closely related species (or strains) coexisting together. These bacteria compete for resources and the competitive exclusion principle predicts that all but the fastest-growing bacteria will go extinct. When exposed to phage, it is predicted that bacterial strains with restriction-modification (RM) systems can circumvent the competitive exclusion principle and reach diversity of the order of the phage burst size. We show that with a trade-off between bacterial growth rates and the strength of their RM systems, the diversity of such an ecosystem can further increase several fold beyond the burst size limit. Moreover, we find that the ratio of the growth rate of a bacterial strain to the imperfection of its RM system is an excellent predictor of (i) whether the strain will go extinct or not, and (ii) the biomass of the strain if it survives. In contrast, the growth rate alone is not a determinant of either of these properties. Our work provides a quantitative example of a model ecosystem where the fitness of a species is determined not by growth rate, but by a trade-off between growth and defence against predators.

}, issn = {2054-5703}, doi = {10.1098/rsos.201118}, author = {Eriksen, Rasmus Skytte and Krishna, Sandeep} } @article {87602, title = {Demographic and ecological correlates of a recovering tiger (Panthera tigris) population: Lessons learnt from 13-years of monitoring}, journal = {BIOLOGICAL CONSERVATION}, year = {2020}, month = {12/2020}, abstract = {

Efforts are on to recover tiger populations range-wide, but we lack suitable metrics to characterise and evaluate such recoveries. Identifying such metrics requires an understanding of tiger population dynamics and its ecological correlates in either recovering populations or those exposed to anthropogenic influences. We monitored a recovering tiger population from 2004 to 2017 in Rajaji National Park, India. Using photographic data and spatial capture-recapture models in an inviolate site vacated by pastoralists (zone 1), we identified demographic parameters of a recovering population. By contrasting it with a site that is presently occupied by pastoralists (zone 3) and one that is isolated (zone 3), we identified conditions facilitating recovery. In zone 1, connected to a large source population in Corbett Tiger Reserve, density increased from 2.08 tigers/100 km(2) to 7.07 tigers/100 km(2) corresponding to an annual growth rate of 4.5\%. Density also increased in zone 2 (2.6 tigers/100 km(2) to 6.22 tigers/100 km(2)), but estimated apparent survival was 0.47 against 0.81 in zone 1. Recovery in zone 1 was accompanied by increased survival of females, while female tenure was shorter in zone 2. Due to the lack of functional connectivity, tigers in zone 3 are facing local extinction. Our results demonstrate that creating inviolate spaces to secure breeding populations and maintaining landscape-wide connectivity to expand breeding cores is critical for recovery. We highlight that relying solely on population increase may lead to unreliable inferences about population performance and instead suggest tracking survival and female land tenure to qualify recovery and success of conservation interventions.

}, doi = {10.1016/j.biocon.2020.108848}, author = {Harihar, Abishek and Pandav, Bivash and Ghosh-Harihar, Mousumi and Goodrich, John} } @article {77441, title = {Description of Bradinopyga konkanensis sp. nov. (Odonata: Anisoptera: Libellulidae) from the coastal region of Maharashtra, India}, journal = {ZOOTAXA}, volume = {4779}, year = {2020}, month = {05/2020}, pages = {65-78}, abstract = {

Bradinopyga konkanensis sp. nov. is described based on three males and one female collected from the coastal region of Maharashtra, India. Important characters are illustrated and compared with morphologically similar species Bradinopyga geminata (Rambur, 1842), Indothemis carnatica (Fabricius, 1798). and Indothemis limbata sita Campion, 1923. Bradinopyga konkanensis sp. nov. is so far the only Western Ghats endemic Odonata species associated with lateritic coastal habitats.

}, doi = {10.11646/zootaxa.4779.1.4}, author = {Joshi, S and Sawant, D} } @article {79863, title = {The desert hamster Phodopus roborovskii (Satunin, 1903) (Rodentia, Cricetidae) from north-western Tibetan plateau, Ladakh, India: an addition to the mammalian fauna of the Indian subcontinent}, journal = {MAMMALIA}, volume = {84}, year = {2020}, month = {05/2020}, pages = {253-258}, abstract = {

During a systematic survey of the small mammals in the relatively unexplored north-western regions of the Tibetan plateau in India, we captured and identified the desert hamster Phodopus roborovskii using molecular phylogenetic methods. We also provide revised distributional estimates for this species using niche modelling (Maxent and 19 bioclimatic variables), taking into account sampling bias. We evaluated suitable habitats for the species, identifying regions in the Trans-Himalayas that may harbour this species. This study improves the knowledge of the desert hamster{\textquoteright}s range and is a new record and an addition to the Indian sub-continental mammalian fauna, similar to 750 km southward extension from its known range.

}, doi = {10.1515/mammalia-2018-0199}, author = {Ramachandran, Vivek and Joshi, Mukta and Ambekar, Mayuresh and Charoo, Samina Amin and Ramakrishnan, Uma} } @article {84074, title = {Design and Synthesis of New Tubulin Polymerization Inhibitors Inspired from Combretastatin A-4: An Anticancer Agent}, journal = {ChemistrySelect}, volume = {5}, year = {2020}, month = {2020/10/08}, pages = {11560 - 11572}, abstract = {

Abstract A series of 30 small hybrid molecules are synthesized inspired from Combretastatin A-4 (CA-4), where ethylene-bridge of CA-4 is replaced with two five-membered heterocyclic rings, viz. isoxazoline and 1, 2, 3-triazole. These are joined by a methylene linker, with substitutions at A and B ? ring position of CA-4. The new molecular entities have shown significant cytotoxicity to cancer cell from the IC50 0.49??M?3.17??M with 1-((4,5-Dihydro-3-(2,5-dimethoxyphenyl)isoxazol-5-yl)methyl)-4-(4-methoxyphenyl)-1H-1,2,3-triazole displayed IC50 0.422{\textpm}0.07??M for A-549 -lung cancer cell line and IC50 0.498{\textpm}0.03??M for MDA-MB-231-breast cancer cell line. The western blot analysis, confocal staining and also by in?vitro tubulin polymerization assay established the target specificity of the molecules as a tubulin polymerization inhibitor. Molecular docking \& Molecular dynamics studies confirmed the binding interaction patterns of these molecules at the Colchicine binding site of tubulin and have correlated the observed experimental result with variation in structure satisfactorily.

}, keywords = {Cancer, Click Chemistry, Colchicine binding site, Combretastatin A-4, Medicinal Chemistry}, isbn = {2365-6549}, url = {https://doi.org/10.1002/slct.202003170}, author = {Sharma, Akanksha and Talimarada, Doddabasappa and Yadav, Umesh Prasad and Singh, Nidhi and Reddy, A. Sudharshan and Bag, Debojyoti and Biswas, Krishna and Baidya, Amit and Borale, Asha N and Shinde, Dhananjay and Singh, Sandeep and Holla, Harish} } @article {74444, title = {DETECTing Merkel Cell Polyomavirus in Merkel Tumors.}, journal = {Front Mol Biosci}, volume = {7}, year = {2020}, month = {2020}, pages = {10}, abstract = {

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post-integration (~80\% cases), or by UV-mediated DNA damage. Interestingly, overall survival of MCV-positive Merkel cell carcinoma patients is better, making this differential information of significant diagnostic and prognostic value. Also, MCV provides a direct target for therapy in MCC patients. Currently, the methods used for diagnosis of MCV in tumors are often discordant and unreliable. Here we used a guided molecular scissors based-DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) technique to develop an molecular diagnostic tool for MCV-positive MCC. DETECTR couples recombinase polymerase based amplification of target MCV DNA with Cas12a mediated detection. CRISPR diagnostics couple specific detection followed by cutting of the pathogenic DNA by the Cas enzyme-gRNA complex, with non-specific cutting of ssDNA that provides a measurable visual cue. To detect MCV DNA in MCC, we designed Cas12a gRNAs targeting the MCV DNA and tested their targeting efficiency, and sensitivity using a fluorophore quencher labeled reporter assay. We show that MCV DETECTR system can detect MCV integrated in Merkel tumor rapidly, specifically and with femto-molar sensitivity. Our study is a preliminary, proof-of-principle analysis showing the use of CRISPR for MCV diagnosis. Further validation in human tumor samples is needed for its clinical use in the near future. This new system is promising and we hope it can be coupled with immunohistochemical studies to diagnose the viral status of MCC in clinics soon.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2020.00010}, author = {Arora, Reety and Gupta, Komal and Vijaykumar, Anjali and Krishna, Sudhir} } @article {82952, title = {Direct involvement of Hsp70 ATP hydrolysis in Ubr1-dependent quality control.}, journal = {Mol Biol Cell}, year = {2020}, month = {2020 Sep 23}, pages = {mbcE20080541}, abstract = {

Chaperones can mediate both protein folding and degradation. This process is referred to as protein triage, which demands study to reveal mechanisms of quality control for both basic scientific and translational purposes. In yeast, many misfolded proteins undergo chaperone dependent ubiquitination by the action of E3 ligases Ubr1 and San1, allowing detailed study of protein triage. In cells, both HSP70 and HSP90 mediated substrate ubiquitination, and the canonical ATP cycle was required for HSP70{\textquoteright}s role: we have found that ATP hydrolysis by HSP70, the nucleotide exchange activity of SSE1, and the action of J proteins are all needed for Ubr1 mediated quality control. To discern if chaperones were directly involved in Ubr1-mediated ubiquitination, we developed a bead-based assay with covalently immobilized but releasable misfolded protein to obviate possible chaperone effects on substrate physical state or transport. In this assay, only HSP70 was required, along with its ATPase cycle and relevant cochaperones, for Ubr1-mediated ubiquitination. The requirement for the HSP70 ATP cycle in ubiquitination suggests a possible model of triage, in which efficiently folded proteins are spared, while slow- or non-folding proteins are iteratively tagged with ubiquitin for subsequent degradation.

}, issn = {1939-4586}, doi = {10.1091/mbc.E20-08-0541}, author = {Singh, Amanjot and Vashistha, Nidhi and Heck, Jarrod and Tang, Xin and Wipf, Peter and Brodsky, Jeffrey L and Hampton, Randolph Y} } @article {78105, title = {Discovery of ANTAR-RNAs and their Mechanism of Action in Mycobacteria.}, journal = {J Mol Biol}, year = {2020}, month = {2020 May 15}, abstract = {

Non-coding RNAs play pivotal roles in bacterial signaling. However, RNAs from certain phyla (specially high-GC actinobacteria) still remain elusive. Here, by re-engineering the existing genome-wide search approach, we discover a family of structurally conserved RNAs that are present ubiquitously across actinobacteria, including mycobacteria. In vitro analysis shows that RNAs belonging to this family bind response-regulator proteins that contain the widely prevalent ANTAR domain. The Mycobacterium tuberculosis ANTAR protein gets phosphorylated by a histidine kinase and interacts with RNA only in its phosphorylated state. These newly identified RNAs reside only in certain transcripts and typically overlap with the ribosome-binding site, regulating translation of these transcripts. In this way, the RNAs directly link signaling pathways to translational control, thus expanding the mechanistic tool kit available for ANTAR-based control of gene expression. In mycobacteria, we find that RNAs targeted by ANTAR proteins majorly encode enzymes of lipid metabolism and associated redox pathways. This now allows us to identify the key genes that mediate ANTAR-dependent control of lipid metabolism. Our study establishes the identity and wide prevalence of ANTAR-target RNAs in mycobacteria, bringing RNA-mediated regulation in these bacteria to the center stage.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2020.05.003}, author = {Mehta, Dolly and Koottathazhath, Anjali and Ramesh, Arati} } @article {83646, title = {Discovery of iron-sensing bacterial riboswitches.}, journal = {Nat Chem Biol}, year = {2020}, month = {2020 Oct 05}, abstract = {

Despite the central role of iron in biology, our understanding of how cells sense iron is limited to protein-dependent mechanisms. Here, we report the discovery of iron-sensing riboswitches (named Sensei). Present across bacterial phyla, these RNAs reside in the 5{\textquoteright} untranslated regions or within coding regions of messenger RNAs (mRNAs) encoding iron-related proteins. These riboswitches bind the reduced form of iron with high specificity. Iron binding causes conformational changes in the riboswitch that alter the accessibility of conserved nucleotides, ultimately enabling a genetic response. Sensei-iron interactions result in increased translation of the riboswitch-associated mRNA in vivo, thus positioning these riboswitches as true metalloregulators. Learning from natural Sensei RNAs, we engineer metal selectivity, successfully converting a nickel/cobalt sensing riboswitch to exclusively bind iron and a Sensei RNA to now exclusively recognize cobalt. We thus define the sequence and structural space of iron-sensing RNAs and open avenues for the design of RNA-based biosensors.

}, issn = {1552-4469}, doi = {10.1038/s41589-020-00665-7}, author = {Bandyopadhyay, Siladitya and Chaudhury, Susmitnarayan and Mehta, Dolly and Ramesh, Arati} } @article {81505, title = {Dispersal and migration have contrasting effects on butterfly flight morphology and reproduction.}, journal = {Biol Lett}, volume = {16}, year = {2020}, month = {2020 Aug}, pages = {20200393}, abstract = {

Movement may fundamentally alter morphology and reproductive states in insects. In long-distance migrants, reproductive diapause is associated with trade-offs between diverse life-history traits such as flight morphology and lifespan. However, many non-diapausing insects engage in shorter resource-driven dispersals. How diapause and other reproductive states alter flight morphology in migrating versus dispersing insects is poorly understood. To find out, we compared flight morphology in different reproductive states of multiple butterfly species. We found that dispersers consisted of ovulating females with higher egg loads compared with non-dispersing females. This trend was in stark contrast with that of migrating female butterflies in reproductive diapause, which made substantially higher investment in flight tissue compared with reproductively active, non-migrating females. Thus, long-distance migration and shorter resource-driven dispersals had contrasting effects on flight morphology and egg loads. By contrast, male flight morphology was not affected by dispersal, migration or associated reproductive states. Thus, dispersal and migration affected resource allocation in flight and reproductive tissue in a sex-specific manner across relatively mobile versus non-dispersing individuals of different species. These findings suggest that dispersals between fragmented habitats may put extra stress on egg-carrying females by increasing their flight burdens.

}, issn = {1744-957X}, doi = {10.1098/rsbl.2020.0393}, author = {Bhaumik, Vaishali and Kunte, Krushnamegh} } @article {85902, title = {Disrupting Plasmodium UIS3-host LC3 interaction with a small molecule causes parasite elimination from host cells.}, journal = {Commun Biol}, volume = {3}, year = {2020}, month = {2020 Nov 19}, pages = {688}, abstract = {

The malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from hepatocytes. Here we show that a small molecule capable of disrupting this interaction triggers parasite elimination in a host cell autophagy-dependent manner. Molecular docking analysis of more than 20 million compounds combined with a phenotypic screen identified one molecule, C4 (4-{[4-(4-{5-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazol-3-yl}benzyl)piperazino]carbonyl}benzonitrile), capable of impairing infection. Using biophysical assays, we established that this impairment is due to the ability of C4 to disrupt UIS3-LC3 interaction, thus inhibiting the parasite{\textquoteright}s ability to evade the host autophagy response. C4 impacts infection in autophagy-sufficient cells without harming the normal autophagy pathway of the host cell. This study, by revealing the disruption of a critical host-parasite interaction without affecting the host{\textquoteright}s normal function, uncovers an efficient anti-malarial strategy to prevent this deadly disease.

}, issn = {2399-3642}, doi = {10.1038/s42003-020-01422-1}, author = {Setua, Sonali and Enguita, Francisco J and Chora, {\^A}ngelo Ferreira and Ranga-Prasad, Harish and Lahree, Aparajita and Marques, Sofia and Sundaramurthy, Varadharajan and Mota, Maria M} } @article {77381, title = {Distinct Evolutionary Origins of Intron Retention Splicing Events in Antiporter Transcripts Relate to Sequence Specific Distinctions in Species.}, journal = {Front Plant Sci}, volume = {11}, year = {2020}, month = {2020}, pages = {267}, abstract = {

The genome of Asian cultivated rice ( L.) shows the presence of six organelle-specific and one plasma membrane () NHX-type cation proton antiporters. Of these, vacuolar-localized is extensively characterized. The genus consists of 27 species and 11 genome-types, with cultivated rice, diploid , having an AA-type genome. orthologous regions (gene organization, 5{\textquoteright} upstream cis elements, amino acid residues/motifs) from closely related AA genomes cluster distinctly from regions from more ancestral BB, FF and KKLL genomes. These sequence-specific distinctions also extend to two separate intron retention (IR) events involving transcripts that occur at the 5{\textquoteright} and 3{\textquoteright} ends of the NHX1 transcripts. We demonstrate that the IR event involving the 5{\textquoteright} UTR is present only in more recently evolved AA genomes while the IR event governing retention of the 13th intron of (terminal intron) is more ancient in origin, also occurring in halophytic wild rice, (KKLL). We also report presence of a retro-copy of the cDNA in the genome of (). Preferential species and tissue specific up- or down-regulation of the correctly spliced transcript/5{\textquoteright} UTR/13th intron-retaining splice variants under salinity was observed. The implications of IR on mRNA stability and ORF diversity in spp. is discussed.

}, issn = {1664-462X}, doi = {10.3389/fpls.2020.00267}, author = {Sellamuthu, Gothandapani and Jegadeeson, Vidya and Sajeevan, Radha Sivarajan and Rajakani, Raja and Parthasarathy, Pavithra and Raju, Kalaimani and Shabala, Lana and Chen, Zhong-Hua and Zhou, Meixue and Sowdhamini, Ramanathan and Shabala, Sergey and Venkataraman, Gayatri} } @article {77437, title = {Distinct regulation of bioenergetics and translation by group I mGluR and NMDAR.}, journal = {EMBO Rep}, volume = {21}, year = {2020}, month = {2020 Jun 04}, pages = {e48037}, abstract = {

Neuronal activity is responsible for the high energy consumption in the brain. However, the cellular mechanisms draining ATP upon the arrival of a stimulus are yet to be explored systematically at the post-synapse. Here, we provide evidence that a significant fraction of ATP is consumed upon glutamate stimulation to energize mGluR-induced protein synthesis. We find that both mGluR and NMDAR alter protein synthesis and ATP consumption with distinct kinetics at the synaptic-dendritic compartments. While mGluR activation leads to a rapid and sustained reduction in neuronal ATP levels, NMDAR activation has no immediate impact on the same. ATP consumption correlates inversely with the kinetics of protein synthesis for both receptors. We observe a persistent elevation in protein synthesis within 5\ minutes of mGluR activation and a robust inhibition of the same within 2\ minutes of NMDAR activation, assessed by the phosphorylation status of eEF2 and metabolic labeling. However, a delayed protein synthesis-dependent ATP expenditure ensues after 15\ minutes of NMDAR stimulation. We identify a central role for AMPK in the correlation between protein synthesis and ATP consumption. AMPK is dephosphorylated and inhibited upon mGluR activation, while it is phosphorylated upon NMDAR activation. Perturbing AMPK activity disrupts receptor-specific modulations of eEF2 phosphorylation and protein synthesis. Our observations, therefore, demonstrate that the regulation of the AMPK-eEF2 signaling axis by glutamate receptors alters neuronal protein synthesis and bioenergetics.

}, issn = {1469-3178}, doi = {10.15252/embr.201948037}, author = {Ghosh Dastidar, Sudhriti and Das Sharma, Shreya and Chakraborty, Sumita and Chattarji, Sumantra and Bhattacharya, Aditi and Muddashetty, Ravi S} } @article {65305, title = {A DNA Aptamer for Cyclic Adenosine Monophosphate that Shows Adaptive Recognition.}, journal = {Chembiochem}, volume = {21}, year = {2020}, month = {2019 May 17}, pages = {157-162}, abstract = {

As a ubiquitous second messenger, cyclic adenosine monophosphate (cAMP) mediates diverse biological processes such as cell growth, inflammation, and metabolism. The ability to probe these pathways would be significantly enhanced if we had a DNA-based sensor for cAMP. Herein, we describe a new, 31-base long single-stranded DNA aptamer for cAMP, denoted caDNApt-1, that was isolated by in vitro selection using systemic evolution of ligands after exponential enrichment (SELEX). caDNApt-1 has an approximately threefold higher affinity for cAMP than ATP, ADP, and AMP. Using non-denaturing gel electrophoresis and fluorescence spectroscopy, we characterized the structural changes caDNApt-1 undergoes upon binding to cAMP and revealed its potential as a cAMP sensor.

}, issn = {1439-7633}, doi = {10.1002/cbic.201900259}, author = {Sharma, Suruchi and Zajac, Matthew and Krishnan, Yamuna} } @article {55791, title = {Dopamine requires unique residues to signal via the serotonin 2A receptor.}, journal = {Neuroscience}, volume = {319-331}, year = {2020}, month = {07/2020}, pages = {319-331}, abstract = {

Serotonin is an important neurotransmitter and neuromodulator. Disruption of the serotonergic system has been implicated in various psychiatric disorders such as schizophrenia and bipolar disorder. Most of the drugs targeting these neurotransmitter systems are classified primarily as agonists or inverse agonists/antagonists, with their described function being limited to activating the canonical signaling pathway(s), or inhibiting the pathway(s) respectively. Previous work with the human 5-HT has shown the receptor to be activated by dopamine, also an endogenous ligand. Dopamine is the cognate ligand of the dopaminergic system, which significantly overlaps with the serotonergic system in the brain. The two systems innervate many of the same brain areas, and the central serotonergic systems also regulate dopamine functions. Our aim was to investigate the downstream signaling set up by the receptor on being activated by dopamine. We show that dopamine is a functionally selective ligand at 5-HT and have examined dopamine as a ligand with respect to some receptor-dependent phenotypes. Our results show that dopamine acts as an agonist at the human serotonin 2A receptor and brings about its activation and internalization. Using in vitro assays, we have established differences in the signaling pathways set up by dopamine as compared to serotonin. Using site-specific mutagenesis we have identified residues important for this functional selectivity, shown by dopamine at this receptor. Our identification of specific residues important in the functional selectivity of dopamine at 5-HT could have far reaching implications for the field of GPCR signaling and drug-design.

}, issn = {1873-7544}, doi = {10.1016/j.neuroscience.2019.03.056}, author = {Soman, Shuchita and Bhattacharya, Aditi and Panicker, Mitradas M} } @article {86474, title = {Downregulation of the tyrosine degradation pathway extends lifespan.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Dec 15}, abstract = {

Aging is characterized by extensive metabolic reprogramming. To identify metabolic pathways associated with aging, we analyzed age-dependent changes in the metabolomes of long-lived . Among the metabolites that changed, levels of tyrosine were increased with age in long-lived flies. We demonstrate that the levels of enzymes in the tyrosine degradation pathway increase with age in wild-type flies. Whole-body and neuronal-specific downregulation of enzymes in the tyrosine degradation pathway significantly extends lifespan, causes alterations of metabolites associated with increased lifespan, and upregulates the levels of tyrosine-derived neuromediators. Moreover, feeding wild-type flies with tyrosine increased their lifespan. Mechanistically, we show that suppression of ETC complex I drives the upregulation of enzymes in the tyrosine degradation pathway, an effect that can be rescued by tigecycline, an FDA-approved drug that specifically suppresses mitochondrial translation. In addition, tyrosine supplementation partially rescued lifespan of flies with ETC complex I suppression. Altogether, our study highlights the tyrosine degradation pathway as a regulator of longevity.

}, issn = {2050-084X}, doi = {10.7554/eLife.58053}, author = {Parkhitko, Andrey A and Ramesh, Divya and Wang, Lin and Leshchiner, Dmitry and Filine, Elizabeth and Binari, Richard and Olsen, Abby L and Asara, John M and Cracan, Valentin and Rabinowitz, Joshua D and Brockmann, Axel and Perrimon, Norbert} } @article {66088, title = {Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane.}, journal = {Mol Biol Cell}, volume = {31}, year = {2020}, month = {03/2020}, pages = {561-579}, abstract = {

Transmembrane adhesion receptors at the cell surface, such as CD44, are often equipped with modules to interact with the extracellular-matrix(ECM) and the intra-cellular cytoskeletal machinery. CD44 has been recently shown to compartmentalize the membrane into domains by acting as membrane pickets, facilitating the function of signaling receptors. While spatial organization and diffusion studies of membrane proteins are usually conducted separately, here we combine observations of organization and diffusion by using high spatio-temporal resolution imaging on living cells to reveal a hierarchical organization of CD44. CD44 is present in a meso-scale meshwork pattern where it exhibits enhanced confinement and is enriched in nano-clusters of CD44 along its boundaries. This nanoclustering is orchestrated by the underlying cortical actin dynamics. Interaction with actin is mediated by specific segments of the intracellular-domain(ICD). This influences the organization of the protein at the nano-scale, generating a selective requirement for formin over Arp2/3-based actin-nucleation machinery. The extracellular-domain(ECD) and its interaction with elements of ECM do not influence the meso-scale organization, but may serve to reposition the meshwork with respect to the ECM. Taken together, our results capture the hierarchical nature of CD44 organization at the cell surface, with active cytoskeleton-templated nano-clusters localized to a meso-scale meshwork pattern. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

}, issn = {1939-4586}, doi = {10.1091/mbc.E18-11-0715}, author = {Sil, Parijat and Mateos, Nicolas and Nath, Sangeeta and Buschow, Sonja and Manzo, Carlo and Suzuki, Kenichi G N and Fujiwara, Takahiro and Kusumi, Akihiro and Garcia-Parajo, Maria F and Mayor, Satyajit} } @article {78017, title = {Dynamics of Genetic Variation in Transcription Factors and Its Implications for the Evolution of Regulatory Networks in Bacteria}, journal = {Nucleic Acids Res}, volume = {48}, year = {2020}, month = {05/2020}, pages = {4100-4114}, abstract = {

The evolution of regulatory networks in Bacteria has largely been explained at macroevolutionary scales through lateral gene transfer and gene duplication. Transcription factors (TF) have been found to be less conserved across species than their target genes (TG). This would be expected if TFs accumulate mutations faster than TGs. This hypothesis is supported by several lab evolution studies which found TFs, especially global regulators, to be frequently mutated. Despite these studies, the contribution of point mutations in TFs to the evolution of regulatory network is poorly understood. We tested if TFs show greater genetic variation than their TGs using whole-genome sequencing data from a large collection of Escherichia coli isolates. TFs were less diverse than their TGs across natural isolates, with TFs of large regulons being more conserved. In contrast, TFs showed higher mutation frequency in adaptive laboratory evolution experiments. However, over long-term laboratory evolution spanning 60 000 generations, mutation frequency in TFs gradually declined after a rapid initial burst. Extrapolating the dynamics of genetic variation from long-term laboratory evolution to natural populations, we propose that point mutations, conferring large-scale gene expression changes, may drive the early stages of adaptation but gene regulation is subjected to stronger purifying selection post adaptation.

}, doi = {10.1093/nar/gkaa162 }, author = {Ali, Farhan and Seshasayee, Aswin} } @article {72074, title = {Early fate of exogenous promoters in E.~coli.}, journal = {Nucleic Acids Res}, year = {2020}, month = {2020 Jan 21}, abstract = {

Gene gain by horizontal gene transfer is a major pathway of genome innovation in bacteria. The current view posits that acquired genes initially need to be silenced and that a bacterial chromatin protein, H-NS, plays a role in this silencing. However, we lack direct observation of the early fate of a horizontally transferred gene to prove this theory. We combine sequencing, flow cytometry and sorting, followed by microscopy to monitor gene expression and its variability after large-scale random insertions of a reporter gene in a population of Escherichia coli bacteria. We find that inserted promoters have a wide range of gene-expression variability related to their location. We find that high-expression clones carry insertions that are not correlated with H-NS binding. Conversely, binding of H-NS correlates with silencing. Finally, while most promoters show a common level of extrinsic noise, some insertions show higher noise levels. Analysis of these high-noise clones supports a scenario of switching due to transcriptional interference from divergent ribosomal promoters. Altogether, our findings point to evolutionary pathways where newly-acquired genes are not necessarily silenced, but may immediately explore a wide range of expression levels to probe the optimal ones.

}, issn = {1362-4962}, doi = {10.1093/nar/gkz1196}, author = {Yousuf, Malikmohamed and Iuliani, Ilaria and Veetil, Reshma T and Seshasayee, Aswin Sai Narain and Sclavi, Bianca and Cosentino Lagomarsino, Marco} } @article {86829, title = {Editorial overview: Insect-inspired engineering: mechanisms, processes and algorithms.}, journal = {Curr Opin Insect Sci}, volume = {42}, year = {2020}, month = {2020 Dec}, pages = {vi-viii}, issn = {2214-5753}, doi = {10.1016/j.cois.2020.11.012}, author = {Sane, Sanjay P} } @article {85180, title = {Effect of doped ZnO nanoparticles on bacterial cell morphology and biochemical composition}, journal = {APPLIED NANOSCIENCE}, year = {2020}, month = {10/2020}, abstract = {

In this work, we show that dopants (silver, copper and iron) significantly increase the antibacterial activity of ZnO nanoparticles. The shapes of ZnO and Ag-ZnO were spherical but it changed to nanoneedles and nanorod-nanosphere composite after doping with Cu and Fe, respectively. The nanoparticles exhibited increased reactive oxygen species (ROS) and metal ion release after doping. Electron microscopy images revealed that small size and sharp features of nanoparticles enable them to internalize and damage the cells, impairing the cell membrane integrity, causing cytoplasm leakage and cell shrinkage. Nanoparticles close to the cell wall indicate that physical attrition of nanoparticles with cells also plays a role in cell damage. The alterations in molecular biochemical composition of bacteria were probed by FTIR and it was seen that the nanoparticles not only affected phosphate and sugar vibrations of cell wall, but also distorted the alpha-helix and beta-sheets of the cellular proteins.

}, doi = {10.1007/s13204-020-01592-8}, author = {Thakur, Shaila and Neogi, Sudarsan} } @article {83640, title = {Enhancing insect flight research with a lab-on-cables.}, journal = {Sci Robot}, volume = {5}, year = {2020}, month = {2020 Aug 26}, abstract = {

A cable-driven robot that tracks flying insects at close range offers a useful method to study insects in free flight.

}, issn = {2470-9476}, doi = {10.1126/scirobotics.abd7941}, author = {Sane, Sanjay P} } @article {78009, title = {Every dog has its prey: Range-wide assessment of links between diet patterns, livestock depredation and human interactions for an endangered carnivore.}, journal = {Sci Total Environ}, volume = {714}, year = {2020}, month = {2020 Apr 20}, pages = {136798}, abstract = {

Livestock depredation is the most ubiquitous type of negative interaction between humans and carnivores. We conducted a range-wide assessment linking diet patterns of the endangered dhole Cuon alpinus, with livestock consumption and human-dhole interactions. We first performed a reanalysis of dhole diet data from all published studies (1973-2013) incorporating a recently-developed non-linear correction factor for quantifying prey biomass consumed. We then determined the relative livestock numbers consumed by dholes over time across its range, compared these with earlier estimates, and investigated the relative importance of wild vs. non-wild prey in dhole diet. Using information from \>70 studies, we explored links between livestock consumption by dholes, availability of wild versus non-wild prey, sympatric depredation-prone carnivores, and people{\textquoteright}s perception of dholes as livestock predators. We found that (a) dhole diet profiles varied regionally, (b) dholes consumed fewer livestock compared to estimates generated using other, widely used methods, (c) livestock consumption by dholes was associated with wild and non-wild prey densities, and number of co-predator species, and (d) people{\textquoteright}s negative perception of dholes was associated with pack sizes, levels of livestock depredation and number of sympatric carnivore species. Global efforts for dhole conservation should involve different strategies based on region-specific realities that account for ecological context as well as human perceptions, which would require well-designed studies of dhole social and population dynamics, and human-dhole interactions. We also call for more such range-wide assessments of livestock depredation by wild canids, complemented with direct investigations of human-canid interactions.

}, keywords = {Animals, Biomass, Carnivora, Diet, Dogs, Humans, Livestock, Predatory Behavior}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2020.136798}, author = {Srivathsa, Arjun and Sharma, Sushma and Oli, Madan K} } @article {84079, title = {Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair.}, journal = {Genome Biol Evol}, year = {2020}, month = {2020 Oct 20}, abstract = {

DNA double-strand breaks (DSBs) are a threat to genome stability. In all domains of life, DSBs are faithfully fixed via homologous recombination. Recombination requires the presence of an uncut copy of duplex DNA which is used as a template for repair. Alternatively, in the absence of a template, cells utilize error-prone Non-homologous end joining (NHEJ). Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. It is unclear as to why many prokaryotes lack this pathway. Towards understanding what could have led to the current distribution of bacterial NHEJ, we carried out comparative genomics and phylogenetic analysis across \~{}6000 genomes. Our results show that this pathway is sporadically distributed across the phylogeny. Ancestral reconstruction further suggests that NHEJ was absent in the eubacterial ancestor, and can be acquired via specific routes. Integrating NHEJ occurrence data for archaea, we also find evidence for extensive horizontal exchange of NHEJ genes between the two kingdoms as well as across bacterial clades. The pattern of occurrence in bacteria is consistent with correlated evolution of NHEJ with key genome characteristics of genome size and growth rate; NHEJ presence is associated with large genome sizes and/or slow growth rates, with the former being the dominant correlate. Given the central role these traits play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by requirement for efficient DSB repair.

}, issn = {1759-6653}, doi = {10.1093/gbe/evaa223}, author = {Sharda, Mohak and Badrinarayanan, Anjana and Seshasayee, Aswin Sai Narain} } @article {78109, title = {Evolutionary constraints on flicker fusion frequency in Lepidoptera.}, journal = {J Comp Physiol A Neuroethol Sens Neural Behav Physiol}, year = {2020}, month = {2020 Jun 11}, abstract = {

Flying insects occupy both diurnal and nocturnal niches, and their visual systems encounter distinct challenges in both conditions. Visual adaptations, such as superposition eyes of moths, enhance sensitivity to low light levels but trade off with spatial and temporal resolution. Conversely, apposition eyes of butterflies enable high spatial resolution but are poorly sensitive in dim light. Although diel activity patterns of insects influence visual processing, their role in evolution of visual systems is relatively unexplored. Lepidopteran insects present an excellent system to study how diel activity patterns and phylogenetic position influence the visual transduction system. We addressed this question by comparing electroretinography measurements of temporal response profiles of diverse Lepidoptera to light stimuli that were flickering at different frequencies. Our data show that the eyes of diurnal butterflies are sensitive to visual stimuli of higher temporal frequencies than nocturnal moths. Hesperiid skippers, which are typically diurnal or crepuscular, exhibit intermediate phenotypes with peak sensitivity across broader frequency range. Across all groups, species within families exhibited similar phenotypes irrespective of diel activity. Thus, Lepidopteran photoreceptors may have diversified under phylogenetic constraints, and shifts in their sensitivity to higher temporal frequencies occurred concomitantly with the evolution of diurnal lifestyles.

}, issn = {1432-1351}, doi = {10.1007/s00359-020-01429-3}, author = {Chatterjee, Payel and Mohan, Umesh and Krishnan, Anand and Sane, Sanjay P} } @article {79806, title = {Extended synaptotagmin regulates membrane contact site structure and lipid transfer function in~vivo.}, journal = {EMBO Rep}, year = {2020}, month = {2020 Jul 27}, pages = {e50264}, abstract = {

Inter-organelle communication between closely apposed membranes is proposed at membrane contact sites (MCS). However, the regulation of MCS structure and their functional relevance in\ vivo remain debated. The extended synaptotagmins (Esyt) are evolutionarily conserved proteins proposed to function at MCS. However, loss of all three Esyts in yeast or mammals shows minimal phenotypes questioning the functional importance of Esyt. We report that in Drosophila photoreceptors, MCS number is regulated by PLCβ activity. Photoreceptors of a null allele of Drosophila extended synaptotagmin (dEsyt) show loss of ER-PM MCS. Loss of dEsyt results in mislocalization of RDGB, an MCS localized lipid transfer protein, required for photoreceptor structure and function, ultimately leading to retinal degeneration. dEsyt depletion enhanced the retinal degeneration, reduced light responses and slower rates of plasma membrane PIP resynthesis seen in rdgB mutants. Thus, dEsyt function and PLCβ signaling regulate ER-PM MCS structure and lipid transfer in Drosophila photoreceptors.

}, issn = {1469-3178}, doi = {10.15252/embr.202050264}, author = {Nath, Vaisaly R and Mishra, Shirish and Basak, Bishal and Trivedi, Deepti and Raghu, Padinjat} } @article {77995, title = {Extreme active matter at high densities.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 May 22}, pages = {2581}, abstract = {

We study the remarkable behaviour of dense active matter comprising self-propelled particles at large P{\'e}clet numbers, over a range of persistence times, from τ\ {\textrightarrow}\ 0, when the active fluid undergoes a slowing down of density relaxations leading to a glass transition as the active propulsion force f reduces, to τ\ {\textrightarrow}\ $\infty$, when as f reduces, the fluid jams at a critical point, with stresses along force-chains. For intermediate τ, a decrease in f drives the fluid through an intermittent phase before dynamical arrest at low f. This intermittency is a consequence of periods of jamming followed by bursts of plastic yielding associated with Eshelby deformations. On the other hand, an increase in f leads to an increase in the burst frequency; the correlated plastic events result in large scale vorticity and turbulence. Dense extreme active matter brings together the physics of glass, jamming, plasticity and turbulence, in a new state of driven classical matter.

}, issn = {2041-1723}, doi = {10.1038/s41467-020-16130-x}, author = {Mandal, Rituparno and Bhuyan, Pranab Jyoti and Chaudhuri, Pinaki and Dasgupta, Chandan and Rao, Madan} } @article {80780, title = {A field-based quantitative analysis of sublethal effects of air pollution on pollinators.}, journal = {Proc Natl Acad Sci U S A}, year = {2020}, month = {2020 Aug 10}, abstract = {

While the impact of air pollution on human health is well studied, mechanistic impacts of air pollution on wild systems, including those providing essential ecosystem services, are largely unknown, but directly impact our health and well-being. India is the world{\textquoteright}s largest fruit producer, second most populous country, and contains 9 of the world{\textquoteright}s 10 most polluted cities. Here, we sampled Giant Asian honey bees, , at locations with varying air pollution levels in Bangalore, India. We observed significant correlations between increased respirable suspended particulate matter (RSPM) deposition and changes in bee survival, flower visitation, heart rate, hemocyte levels, and expression of genes related to lipid metabolism, stress, and immunity. Lab-reared exposed to these same sites also exhibited similar molecular and physiological differences. Our study offers a quantitative analysis on the current impacts of air pollution on insects, and indicates the urgency for more nonhuman studies to accurately assess the effects of pollution on our natural world.

}, issn = {1091-6490}, doi = {10.1073/pnas.2009074117}, author = {Thimmegowda, Geetha G and Mullen, Susan and Sottilare, Katie and Sharma, Ankit and Mohanta, Saptashi Soham and Brockmann, Axel and Dhandapany, Perundurai S and Olsson, Shannon B} } @article {74441, title = {Fire differentially affects mortality and seedling regeneration of three woody invaders in forest-grassland mosaics of the southern Western Ghats, India}, journal = {BIOLOGICAL INVASIONS}, year = {2020}, month = {01/2020}, abstract = {

Invasion by exotic woody species is a major concern in grasslands worldwide. Woody invasions pose a particularly serious threat to forest-grassland mosaics globally, but the factors influencing the success of woody species in these systems, including the role of disturbances such as fire, are not well understood. In this study, we evaluated the role of fire in influencing mortality and regeneration success of three globally widespread woody invasives, Acacia mearnsii (black wattle), Cytisus scoparius (scotch broom) and Ulex europaeus (gorse) in the montane forest-grassland mosaics of the Nilgiri Biosphere Reserve in the Western Ghats biodiversity hotspot, India. Our results indicate that mortality and regeneration responses to fire are species-specific. Fire-induced adult mortality was highest in scotch broom and lowest in gorse, and high, but variable in wattle. Burning greatly increased the abundance of gorse and wattle seedlings, but only marginally increased scotch broom seedling abundance. Fire effects on invasive seedling densities were most pronounced at the edges of invasive patches. Overall, our results indicate that fires are likely to differentially affect invasion patterns of these three species, with fire potentially encouraging invasion by gorse and wattle and discouraging invasion by scotch broom.

}, doi = { 10.1007/s10530-020-02207-7}, author = {Sriramamurthy, R.T. and Bhalla, R. S. and Sankaran, Mahesh} } @article {79732, title = {A Fluorescence-Based Assay to Monitor SUMOylation in Real-Time.}, journal = {Curr Protoc Protein Sci}, volume = {101}, year = {2020}, month = {2020 Sep}, pages = {e111}, abstract = {

The small ubiquitin-like modifier (SUMO) is an important post-translational modifier that regulates various cellular processes. Extensive investigations have been made to comprehend the enzymatic process and consequence of SUMOylation. In vitro SUMOylation assays are invaluable for understanding the fundamental mechanisms of SUMOylation. A majority of these assays monitor changes in the size of the substrate upon SUMO conjugation. Current methods typically detect the size difference through SDS-PAGE and western blots, which makes these methods cumbersome, error-prone, and time-consuming. Here, we describe a fluorescence-based assay for real-time detection of SUMOylation. In the method, a fluorophore-tagged substrate is used in the SUMOylation reaction. Upon SUMOylation, the size and correlation time (τ ) of the substrate increases, and so does its anisotropy. The rate of change in anisotropy with time reflects the efficiency of the SUMOylation machinery. The real-time SUMOylation assay protocol is elegant, time-saving, and less prone to errors. {\textcopyright} 2020 Wiley Periodicals LLC. Basic Protocol: Fluorescent anisotropy-based in vitro SUMOylation assay.

}, issn = {1934-3663}, doi = {10.1002/cpps.111}, author = {Tripathi, Vasvi and Das, Ranabir} } @article {85183, title = {Foraging niche differentiation among sympatric woodpecker species in forests of north-western India}, journal = {ACTA ORNITHOLOGICA}, volume = {55}, year = {2020}, month = {11/2020}, pages = {88-100}, abstract = {

The sub-Himalayan dipterocarp forests of subtropical region in northwest India support 17 species of woodpecker. From a conservation perspective it is necessary to assess the ecological requirements of woodpeckers in these biologically diverse landscapes, which are experiencing habitat modification and decline in some woodpeckers. We studied the foraging niche differentiation among ten sympatric woodpeckers in the sub-Himalayan forests of northwest India: Dendrocopos canicapillus, D. macei, Picus cldorolophus, P. xanthopygaeus, P. can us, Dinopium shorii, D. benghalense, Chrysophlegma [Picus] flavinucha, Chrysocolaptes lucidus, and Mulleripicus pulverulentus. We examined the foraging site preferences of individual woodpecker species and explored the role of inter-specific differences in foraging behaviour as a possible mechanism for their coexistence. Observations on foraging woodpeckers were taken vis-a-vis the following niche dimensions: diameter of the foraging tree, height of the foraging bird, type of substrate on which it was foraging, vertical position with respect to canopy, condition of the forage tree and condition of the substrate. Distinct preferences were evident among species in their foraging tree diameters, foraging heights, vertical positions, and choice of substrate type, while preference for dead substrates was not an important distinguishing factor. Species that overlapped in one dimension generally segregated along other dimensions. Niche segregation in forage tree diameter was associated with body weight. Based on their overall niche overlaps species could broadly be differentiated into groups according to body size viz. small (3 species), medium (3 species), large (3 species), and very large (1 species). Our study demonstrates that differentiation in foraging may be a likely mechanism for coexistence of sympatric woodpeckers in this region. Given that larger species prefer larger substrates, removal of mature trees could affect their abundance, and homogenisation of stand structure could lead to impoverishment of woodpecker diversity.

}, doi = {10.3161/00016454AO2020.55.1.009}, author = {Kumar, Raman and Shahabuddin, Ghazala and Kumar, Ajith} } @article {79862, title = {Forest cover and fruit crop size differentially influence frugivory of select rainforest tree species in Western Ghats, India}, journal = {BIOTROPICA}, year = {2020}, month = {06/2020}, abstract = {

Forest fragmentation and habitat loss are major disruptors of plant-frugivore interactions, affecting seed dispersal and altering recruitment patterns of the dependent tree species. In a heterogeneous production landscape (primarily tea and coffee plantations) in the southern Western Ghats, India, we examined effects of surrounding forest cover and fruit crop size on frugivory of four rainforest bird-dispersed tree species (N = 131 trees, \>= 30 trees per species, observed for 623 hr). Frugivore composition differed among the four tree species with the large-seededCanarium strictumandMyristica dactyloidesbeing exclusively dependent on large-bodied avian frugivores, whereas medium-seededPersea macranthaandHeynea trijugawere predominantly visited by small-bodied and large-bodied avian frugivores, respectively. Using the seed-dispersal-effectiveness framework, we identified effective frugivores and examined their responses to forest cover and fruit crop size. Results were idiosyncratic and were governed by plant and frugivore traits. Visitations to medium-seededPerseahad a positive relationship with forest cover but the relationship was negative for the large-seededMyristica. In addition, two of the three effective frugivores forPersearesponded to the interactive effect of forest cover and fruit crop size.Frugivore visitations toHeyneawere not related to forest cover or fruit crop, and there were too few visitations toCanariumto discern any trends.These results highlight the context-specific responses of plant-frugivore interactions to forest cover and fruit crop size influenced by plant and frugivore traits.

}, doi = {10.1111/btp.12810}, author = {Gopal, Abhishek and Mudappa, Divya and Raman, TRS and Naniwadekar, Rohit} } @article {77444, title = {Frost maintains forests and grasslands as alternate states in a montane tropical forest-grassland mosaic; but alien tree invasion and warming can disrupt this balance}, journal = {JOURNAL OF ECOLOGY}, volume = {108}, year = {2020}, month = {01/2020}, pages = {122-132}, abstract = {

1. Forest-grassland mosaics, with abrupt boundaries between the two vegetation types, occur across the globe. Fire and herbivory are widely considered primary drivers that maintain these mosaics by limiting tree establishment in grasslands, while edaphic factors and frosts are generally considered to be secondary factors that reinforce these effects. However, the relative importance of these drivers likely varies across systems. In particular, although frost is known to occur in many montane tropical mosaics, experimental evidence for its role as a driving factor is limited.

2. We used replicated in situ transplant and warming experiments to examine the role of microclimate (frost and freezing temperatures) and soil in influencing germination and seedling survival of both native forest trees and alien invasive Acacia trees in grasslands of a tropical montane forest-grassland mosaic in the Western Ghats of southern India.

3. Seed germination of both native and alien tree species was higher in grasslands regardless of soil type, indicating that germination was not the limiting stage to tree establishment. However, irrespective of soil type, native seedlings in grasslands incurred high mortality following winter frosts and freezing temperatures relative to native seedlings in adjoining forests where freezing temperatures did not occur. Seedling survival through the tropical winter was thus a primary limitation to native tree establishment in grasslands. In contrast, alien Acacia seedlings in grasslands incurred much lower levels of winter mortality. Experimental night-time warming in grasslands significantly enhanced over-winter survival of all tree seedlings, but increases were much greater for alien Acacia than for native tree seedlings.

4. Synthesis. Our results provide evidence for a primary role for frost and freezing temperatures in limiting tree establishment in grasslands of this tropical montane forest-grassland mosaic. Future increases in temperature are likely to release trees from this limitation and favour tree expansion into grasslands, with rates of expansion of non-native Acacia likely to be much greater than that of native trees. We suggest that studies of frost limitation to plant establishment are needed across a range of tropical ecosystems to re-evaluate the general importance of frost as a driver of vegetation transitions in the tropics.

}, doi = {10.1111/1365-2745.13239}, author = {Joshi, AA and Ratnam, J and Sankaran, M} } @article {78000, title = {Functional diversity in a lipidome.}, journal = {Proc Natl Acad Sci U S A}, volume = {117}, year = {2020}, month = {2020 May 26}, pages = {11191-11193}, issn = {1091-6490}, doi = {10.1073/pnas.2004764117}, author = {Raghu, Padinjat} } @article {73039, title = {A Fyn biosensor reveals pulsatile, spatially localized kinase activity and signaling crosstalk in live mammalian cells.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Feb 04}, abstract = {

Cell behavior is controlled through spatio-temporally localized protein activity. Despite unique and often contradictory roles played by Src-family-kinases (SFKs) in regulating cell physiology, activity patterns of individual SFKs have remained elusive. Here, we report a biosensor for specifically visualizing active conformation of SFK-Fyn in live cells. We deployed combinatorial library screening to isolate a binding-protein (F29) targeting activated Fyn. Nuclear-magnetic-resonance (NMR) analysis provides the structural basis of F29 specificity for Fyn over homologous SFKs. Using F29, we engineered a sensitive, minimally-perturbing fluorescence-resonance-energy-transfer (FRET) biosensor () that reveals cellular Fyn activity to be spatially localized, pulsatile and sensitive to adhesion/integrin signaling. Strikingly, growth factor stimulation further enhanced Fyn activity in pre-activated intracellular zones. However, inhibition of focal-adhesion-kinase activity not only attenuates Fyn activity, but abolishes growth-factor modulation. imaging uncovers spatially organized, sensitized signaling clusters, direct crosstalk between integrin and growth-factor-signaling, and clarifies how compartmentalized Src-kinase activity may drive cell fate.

}, issn = {2050-084X}, doi = {10.7554/eLife.50571}, author = {Mukherjee, Ananya and Singh, Randhir and Udayan, Sreeram and Biswas, Sayan and Reddy, Pothula Purushotham and Manmadhan, Saumya and George, Geen and Kumar, Shilpa and Das, Ranabir and Rao, Balaji M and Gulyani, Akash} } @article {82949, title = {Geckos in the granite: two new geckos (Squamata: Gekkonidae) from rocky, scrub habitats in Rishi Valley, Andhra Pradesh, India}, journal = {ZOOTAXA}, volume = {4838}, year = {2020}, month = {08/2020}, pages = {451-474}, abstract = {

Two new species of geckos from the genera Cnemaspis and Hemidactylus are described from a granite outcrop in the Rishi Valley, Chittoor District, Andhra Pradesh, India. Cnemaspis rishivalleyensis sp. nov. and Hemidactylus rishivalleyensis sp. nov. are presently known only from their type locality and am 8.7 \% and 10.9 \% divergent from their closest known sister species, respectively. The new species are allied to the mysoriensis and murrayi clades of South Asian Cnemaspis and the bmokii group of Indian Hemidactylus, respectively. The two new species can be diagnosed from regional congeners by the number and arrangement of femoral and precloacal pores and poreless scales separating these series, body size, the number of tubercles in paravertebral rows, the number of enlarged tubercles around mid-body, the number of ventral scales across mid-body, the number of lamellae beneath digit IV of pes and manus, and subtle differences in colour pattern. Four endemic geckos now have their type localities within 10 km of each other, Cnemaspis graniticola and Cyrtodactylus rishivalleyensis from Horsley Hills and the two new species from Rishi Valley. The two new species are also the third endemic species each of Cnemaspis and Hemidactylus from Andhra Pradesh.

}, doi = {10.11646/zootaxa.4838.4.1}, author = {Agarwal, Ishan and Thackeray, Tejas and Khandekar, Akshay} } @article {84576, title = {General destabilizing effects of eutrophication on grassland productivity at multiple spatial scales.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 10 23}, pages = {5375}, abstract = {

Eutrophication is a widespread environmental change that usually reduces the stabilizing effect of plant diversity on productivity in local communities. Whether this effect is scale dependent remains to be elucidated. Here, we determine the relationship between plant diversity and temporal stability of productivity for 243 plant communities from 42 grasslands across the globe and quantify the effect of chronic fertilization on these relationships. Unfertilized local communities with more plant species exhibit greater asynchronous dynamics among species in response to natural environmental fluctuations, resulting in greater local stability (alpha stability). Moreover, neighborhood communities that have greater spatial variation in plant species composition within sites (higher beta diversity) have greater spatial asynchrony of productivity among communities, resulting in greater stability at the larger scale (gamma stability). Importantly, fertilization consistently weakens the contribution of plant diversity to both of these stabilizing mechanisms, thus diminishing the positive effect of biodiversity on stability at differing spatial scales. Our findings suggest that preserving grassland functional stability requires conservation of plant diversity within and among ecological communities.

}, issn = {2041-1723}, doi = {10.1038/s41467-020-19252-4}, author = {Hautier, Yann and Zhang, Pengfei and Loreau, Michel and Wilcox, Kevin R and Seabloom, Eric W and Borer, Elizabeth T and Byrnes, Jarrett E K and Koerner, Sally E and Komatsu, Kimberly J and Lefcheck, Jonathan S and Hector, Andy and Adler, Peter B and Alberti, Juan and Arnillas, Carlos A and Bakker, Jonathan D and Brudvig, Lars A and Bugalho, Miguel N and Cadotte, Marc and Caldeira, Maria C and Carroll, Oliver and Crawley, Mick and Collins, Scott L and Daleo, Pedro and Dee, Laura E and Eisenhauer, Nico and Eskelinen, Anu and Fay, Philip A and Gilbert, Benjamin and Hansar, Amandine and Isbell, Forest and Knops, Johannes M H and MacDougall, Andrew S and McCulley, Rebecca L and Moore, Joslin L and Morgan, John W and Mori, Akira S and Peri, Pablo L and Pos, Edwin T and Power, Sally A and Price, Jodi N and Reich, Peter B and Risch, Anita C and Roscher, Christiane and Sankaran, Mahesh and Sch{\"u}tz, Martin and Smith, Melinda and Stevens, Carly and Tognetti, Pedro M and Virtanen, Risto and Wardle, Glenda M and Wilfahrt, Peter A and Wang, Shaopeng} } @article {81504, title = {Genetic diversity targets and indicators in the CBD post-2020 Global Biodiversity Framework must be improved}, journal = {BIOLOGICAL CONSERVATION}, volume = {248}, year = {2020}, month = {08/2020}, abstract = {

The 196 parties to the Convention on Biological Diversity (CBD) will soon agree to a post-2020 global framework for conserving the three elements of biodiversity (genetic, species, and ecosystem diversity) while ensuring sustainable development and benefit sharing. As the most significant global conservation policy mechanism, the new CBD framework has far-reaching consequences- it will guide conservation actions and reporting for each member country until 2050. In previous CBD strategies, as well as other major conservation policy mechanisms, targets and indicators for genetic diversity (variation at the DNA level within species, which facilitates species adaptation and ecosystem function) were undeveloped and focused on species of agricultural relevance. We assert that, to meet global conservation goals, genetic diversity within all species, not just domesticated species and their wild relatives, must be conserved and monitored using appropriate metrics. Building on suggestions in a recent Letter in Science (Laikre et al., 2020) we expand argumentation for three new, pragmatic genetic indicators and modifications to two current indicators for maintaining genetic diversity and adaptive capacity of all species, and provide guidance on their practical use. The indicators are: 1) the number of populations with effective population size above versus below 500, 2) the proportion of populations maintained within species, 3) the number of species and populations in which genetic diversity is monitored using DNA-based methods. We also present and discuss Goals and Action Targets for post-2020 biodiversity conservation which are connected to these indicators and underlying data. These pragmatic indicators and goals have utility beyond the CBD; they should benefit conservation and monitoring of genetic diversity via national and global policy for decades to come.

}, doi = {10.1016/j.biocon.2020.108654}, author = {Hoban, Sean and Bruford, Michael and Jackson, JD and Lopes-Fernandes, M and ....... and Ramakrishnan, Uma and et al} } @article {67833, title = {A Genetic Screen in Drosophila To Identify Novel Regulation of Cell Growth by Phosphoinositide Signaling.}, journal = {G3 (Bethesda)}, volume = {10}, year = {2020}, month = {2019 Nov 08}, pages = {57-67}, abstract = {

Phosphoinositides are lipid signaling molecules that regulate several conserved sub-cellular processes in eukaryotes, including cell growth. Phosphoinositides are generated by the enzymatic activity of highly specific lipid kinases and phosphatases. For example, the lipid PIP, the Class I PI3 kinase that generates it and the phosphatase PTEN that metabolizes it are all established regulators of growth control in metazoans. To identify additional functions for phosphoinositides in growth control, we performed a genetic screen to identify proteins which when depleted result in altered tissue growth. By using RNA-interference mediated depletion coupled with mosaic analysis in developing eyes, we identified and classified additional candidates in the developing eye that regulate growth either cell autonomously or via cell-cell interactions. We report three genes: , and that are important for growth regulation and suggest that these are likely to act via cell-cell interactions in the developing eye. Our findings define new avenues for the understanding of growth regulation in metazoan tissue development by phosphoinositide metabolizing proteins.

}, issn = {2160-1836}, doi = {10.1534/g3.119.400851}, author = {Janardan, Vishnu and Sharma, Sanjeev and Basu, Urbashi and Raghu, Padinjat} } @article {84941, title = {Genetically encoded live-cell sensor for tyrosinated microtubules.}, journal = {J Cell Biol}, volume = {219}, year = {2020}, month = {2020 Oct 05}, abstract = {

Microtubule cytoskeleton exists in various biochemical forms in different cells due to tubulin posttranslational modifications (PTMs). Tubulin PTMs are known to affect microtubule stability, dynamics, and interaction with MAPs and motors in a specific manner, widely known as tubulin code hypothesis. At present, there exists no tool that can specifically mark tubulin PTMs in living cells, thus severely limiting our understanding of their dynamics and cellular functions. Using a yeast display library, we identified a binder against terminal tyrosine of α-tubulin, a unique PTM site. Extensive characterization validates the robustness and nonperturbing nature of our binder as tyrosination sensor, a live-cell tubulin nanobody specific towards tyrosinated microtubules. Using this sensor, we followed nocodazole-, colchicine-, and vincristine-induced depolymerization events of tyrosinated microtubules in real time and found each distinctly perturbs the microtubule polymer. Together, our work describes a novel tyrosination sensor and its potential applications to study the dynamics of microtubule and their PTM processes in living cells.

}, issn = {1540-8140}, doi = {10.1083/jcb.201912107}, author = {Kesarwani, Shubham and Lama, Prakash and Chandra, Anchal and Reddy, P Purushotam and Jijumon, A S and Bodakuntla, Satish and Rao, Balaji M and Janke, Carsten and Das, Ranabir and Sirajuddin, Minhajuddin} } @article {86476, title = {A genome engineering resource to uncover principles of cellular organization and tissue architecture by lipid signalling.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Dec 15}, abstract = {

Phosphoinositides (PI) are key regulators of cellular organization in eukaryotes and genes that tune PI signalling are implicated in human disease mechanisms. Biochemical analyses and studies in cultured cells have identified a large number of proteins that can mediate PI signalling. However, the role of such proteins in regulating cellular processes and development in metazoans remains to be understood. Here we describe a set of CRISPR based genome engineering tools that allow the manipulation of each of these proteins with spatial and temporal control during metazoan development. We demonstrate the use of these reagents to deplete a set of 103 proteins individually in the eye and identify several new molecules that control eye development. Our work demonstrates the power of this resource in uncovering the molecular basis of tissue homeostasis during normal development and in human disease biology.

}, issn = {2050-084X}, doi = {10.7554/eLife.55793}, author = {Trivedi, Deepti and Cm, Vinitha and Bisht, Karishma and Janardan, Vishnu and Pandit, Awadhesh and Basak, Bishal and H, Shwetha and Ramesh, Navyashree and Raghu, Padinjat} } @article {87278, title = {Genome-scale reconstruction of Gcn4/ATF4 networks driving a growth program}, journal = {PLoS Genet}, volume = {16}, year = {2020}, month = {12/2020}, pages = {e1009252}, abstract = {

Growth and starvation are considered opposite ends of a spectrum. To sustain growth, cells use coordinated gene expression programs and manage biomolecule supply in order to match the demands of metabolism and translation. Global growth programs complement increased ribosomal biogenesis with sufficient carbon metabolism, amino acid and nucleotide biosynthesis. How these resources are collectively managed is a fundamental question. The role of the Gcn4/ATF4 transcription factor has been best studied in contexts where cells encounter amino acid starvation. However, high Gcn4 activity has been observed in contexts of rapid cell proliferation, and the roles of Gcn4 in such growth contexts are unclear. Here, using a methionine-induced growth program in yeast, we show that Gcn4/ATF4 is the fulcrum that maintains metabolic supply in order to sustain translation outputs. By integrating matched transcriptome and ChIP-Seq analysis, we decipher genome-wide direct and indirect roles for Gcn4 in this growth program. Genes that enable metabolic precursor biosynthesis indispensably require Gcn4; contrastingly ribosomal genes are partly repressed by Gcn4. Gcn4 directly binds promoter-regions and transcribes a subset of metabolic genes, particularly driving lysine and arginine biosynthesis. Gcn4 also globally represses lysine and arginine enriched transcripts, which include genes encoding the translation machinery. The Gcn4 dependent lysine and arginine supply thereby maintains the synthesis of the translation machinery. This is required to maintain translation capacity. Gcn4 consequently enables metabolic-precursor supply to bolster protein synthesis, and drive a growth program. Thus, we illustrate how growth and starvation outcomes are both controlled using the same Gcn4 transcriptional outputs that function in distinct contexts.

}, doi = {10.1371/journal.pgen.1009252}, author = {Srinivasan, R and Walvekar, AS and Rashida, Z and Seshasayee, A and Laxman, S} } @article {80779, title = {Geographical distribution of the giant honey bee Smith, 1871 (Hymenoptera, Apidae).}, journal = {Zookeys}, volume = {951}, year = {2020}, month = {2020}, pages = {67-81}, abstract = {

Worldwide pollinator declines have dramatically increased our need to survey and monitor pollinator distributions and abundances. The giant honey bee, , is one of the important pollinators at higher altitudes of the Himalayas. This species has a restricted distribution along the Himalayas and neighbouring mountain ranges of Asia. Previous assessments of its distribution, published more than 20 years ago, were based on museum specimens. Since then, 244 additional localities have been revealed through field trips by the authors, publications, and websites. We present a revised distribution for that better defines its range and extends it eastward to the mountains of northern Vietnam, southward along the Arakan Mountains to west-central Myanmar, into the Shillong Hills of Meghalaya, India, and northwestward in Uttarakhand, India. This species is generally found at elevations between 1000-3000 m a.s.l.. In northeastern India colonies occur during summer at sites as low as 850 m a.s.l. and some lower elevation colonies maintain their nests throughout the winter. Finally, we report three regions in Arunachal Pradesh, India, and nine locations in northern Vietnam, where we observed workers of and foraging sympatrically; their co-occurrence supports the species status of .

}, issn = {1313-2989}, doi = {10.3897/zookeys.951.49855}, author = {Kitnya, Nyaton and Prabhudev, M V and Bhatta, Chet Prasad and Pham, Thai Hong and Nidup, Tshering and Megu, Karsing and Chakravorty, Jharna and Brockmann, Axel and Otis, G W} } @article {78104, title = {A glance into the evolution of template-free protein structure prediction methodologies.}, journal = {Biochimie}, volume = {175}, year = {2020}, month = {2020 May 15}, pages = {85-92}, abstract = {

Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (\>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.

}, issn = {1638-6183}, doi = {10.1016/j.biochi.2020.04.026}, author = {Dhingra, Surbhi and Sowdhamini, Ramanathan and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard} } @article {74445, title = {Global mistranslation increases cell survival under stress in Escherichia coli.}, journal = {PLoS Genet}, volume = {16}, year = {2020}, month = {2020 Mar 09}, pages = {e1008654}, abstract = {

Mistranslation is typically deleterious for cells, although specific mistranslated proteins can confer a short-term benefit in a particular environment. However, given its large overall cost, the prevalence of high global mistranslation rates remains puzzling. Altering basal mistranslation levels of Escherichia coli in several ways, we show that generalized mistranslation enhances early survival under DNA damage, by rapidly activating the SOS response. Mistranslating cells maintain larger populations after exposure to DNA damage, and thus have a higher probability of sampling critical beneficial mutations. Both basal and artificially increased mistranslation increase the number of cells that are phenotypically tolerant and genetically resistant under DNA damage; they also enhance survival at high temperature. In contrast, decreasing the normal basal mistranslation rate reduces cell survival. This wide-ranging stress resistance relies on Lon protease, which is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance indicate surprising coordination between intracellular stress responses and suggest a novel hypothesis to explain high global mistranslation rates.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1008654}, author = {Samhita, Laasya and Raval, Parth K and Agashe, Deepa} } @article {78110, title = {GLOMERULUS-SELECTIVE REGULATION OF A CRITICAL PERIOD FOR INTERNEURON PLASTICITY IN THE ANTENNAL LOBE.}, journal = {J Neurosci}, year = {2020}, month = {2020 Jun 12}, abstract = {

Several features of the adult nervous systems develop in a "critical period," (CP) during which high levels of plasticity allow neural circuits to be tuned for optimal performance. Through an analysis of long-term olfactory habituation (LTH) in female , we provide new insight into mechanisms by which CPs are regulated LTH manifests as a persistently reduced behavioural response to an odorant encountered for four continuous days and occurs together with the growth of specific, odorant-responsive glomeruli in the antennal lobe. We show that the CP for behavioral and structural plasticity induced by ethyl butyrate (EB) or carbon dioxide (CO) closes within 48 hours after eclosion. The elaboration of excitatory projection neuron (PN) processes likely contribute to glomerular volume increases: both occur together and similarly require cAMP signalling in the antennal lobe inhibitory local interneurons (iLNs). Further, the CP for structural plasticity could be extended beyond 48 hours if EB- or CO-responsive olfactory sensory neurons (OSNs) are silenced after eclosion; thus, OSN activity is required for closing the CP. Strikingly, silencing of glomerulus-selective OSNs extends the CP for structural plasticity only in respective target glomeruli. This indicates existence of a local, short-range mechanism for regulating CP closure. Such a local mechanism for CP regulation can explain why plasticity induced by the odorant geranyl acetate (GA, which is attractive) shows no CP although it involves the same core plasticity mechanisms as CO and EB. Local control of critical-period closure mechanisms can potentially impart evolutionarily adaptive, odorant-specific features to behavioral plasticity.The critical period for plasticity represents a stage of life at which animals learn specific tasks or features with particular facility. This work provides fresh evidence that mechanisms for regulating critical periods are broadly conserved across evolution. Thus, a critical period for long-term olfactory habituation in Drosophila which closes early in adulthood can, like the critical period for ocular dominance plasticity in mammals, be extended by blocking sensory neurons early in life. Further observations show that critical periods for plasticity can be regulated by spatially restricted mechanisms, potentially allowing varied critical periods for plasticity to stimuli of different ethological relevance.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.2192-19.2020}, author = {Chodankar, Ankita and Sadanandappa, Madhumala K and VijayRaghavan, K and Ramaswami, Mani} } @article {79780, title = {Golgi compartments enable controlled biomolecular assembly using promiscuous enzymes.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Jun 29}, abstract = {

The synthesis of eukaryotic glycans - branched sugar oligomers attached to cell-surface proteins and lipids - is organized like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products. However, this variability is tightly controlled: a given eukaryotic protein type is typically associated with a narrow, specific glycan oligomer profile. Here, we use ideas from the mathematical theory of self-assembly to enumerate the enzymatic causes of oligomer variability and show how to eliminate each cause. We rigorously demonstrate that cells can specifically synthesize a larger repertoire of glycan oligomers by partitioning promiscuous enzymes across multiple Golgi compartments. This places limits on biomolecular assembly: glycan microheterogeneity becomes unavoidable when the number of compartments is limited, or enzymes are excessively promiscuous.

}, issn = {2050-084X}, doi = {10.7554/eLife.49573}, author = {Jaiman, Anjali and Thattai, Mukund} } @article {77448, title = {Granite boulders act as deep-time climate refugia: A Miocene divergent clade of rupicolous Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from the Mysore Plateau, India, with descriptions of three new species}, journal = {JOURNAL OF ZOOLOGICAL SYSTEMATICS AND EVOLUTIONARY RESEARCH}, year = {2020}, month = {05/2020}, abstract = {

We describe a divergent clade and three new rupicolous species of dwarf geckos of the genus Cnemaspis from the Mysore Plateau, southern India. Cnemaspis bangara sp. nov., C. graniticola sp. nov., and C. yelagiriensis sp. nov. differ from each other by 9\%-18\% uncorrected ND2 sequence divergence and other South Asian Cnemaspis by 17\%-33\% and are morphologically distinguishable from all regional congeners and each other. The new species are known from only granite boulders in montane habitats (\>1,000 m asl.), just 60-120 km straight-line distance apart from each other. A fossil-calibrated timetree and ancestral area reconstructions indicate South Asian Cnemaspis originated in Western Ghats forests with initial divergence in the Paleocene-Eocene making it perhaps the oldest Indian squamate clade. Cnemaspis that occur in Peninsular India in the dry zone outside the Western Ghats form three independently derived clades that occur in significantly warmer and drier habitats than those in the Western Ghats. The discovery of a Miocene divergent clade from rocky hills on the southern edge of the Mysore Plateau reveals these habitats as novel, long-term climate refugia. This adds to the body of work revealing ancient origins of taxa in the Indian dry zone and supports the Mysore Plateau as an important and overlooked hot spot of lizard biodiversity.

}, doi = {10.1111/jzs.12391}, author = {Agarwal, I and Thackeray, Tejas and Pal, S and Khandekar, A} } @article {73041, title = {Grasses continue to trump trees at soil carbon sequestration following herbivore exclusion in a semi-arid African savanna.}, journal = {Ecology}, year = {2020}, month = {2020 Feb 06}, pages = {e03008}, abstract = {

While studies have shown that mammalian herbivores often limit aboveground carbon storage in savannas, their effects on belowground soil carbon storage remains unclear. Using three sets of long-term, large herbivore exclosures with paired controls, we asked how almost two decades of herbivore removal from a semi-arid savanna in Laikipia, Kenya affected aboveground (woody and grass) and belowground soil carbon sequestration, and determined the major source (C vs. C ) of belowground carbon sequestered in soils with and without herbivores present. Large herbivore exclusion, which included a diverse community of grazers, browsers, and mixed-feeding ungulates, resulted in significant increases in grass cover (~22\%), woody basal area (~8 m ha ) and woody canopy cover (31\%), translating to a ~8.5 t ha increase in aboveground carbon over two decades. Herbivore exclusion also led to a 54\% increase (20.5 t ha ) in total soil carbon to 30 cm depth, with ~71\% of this derived from C grasses (vs. ~76\% with herbivores present) despite substantial increases in woody cover. We attribute this continued high contribution of C grasses to soil C sequestration to the reduced offtake of grass biomass with herbivore exclusion together with the facilitative influence of open sparse woody canopies (e.g. Acacia spp.) on grass cover and productivity in this semi-arid system.

}, issn = {1939-9170}, doi = {10.1002/ecy.3008}, author = {Wigley, Benjamin J and Augustine, David J and Coetsee, Corli and Ratnam, Jayashree and Sankaran, Mahesh} } @article {85847, title = {Grazing and climate change have site-dependent interactive effects on vegetation in Asian montane rangelands}, journal = {JOURNAL OF APPLIED ECOLOGY}, year = {2020}, month = {11/2020}, abstract = {

Climate over Asian montane rangelands is changing faster than the global average, posing serious threats to the future of the region{\textquoteright}s livestock-based economies and cultures. Effects of climate change on rangeland vegetation likely depend on grazing by herbivores but the potential responses of vegetation to such changes in climate and grazing regimes remain unclear.

We examined vegetation responses to experimentally simulated climate change (warming, drought and increased rainfall) and grazing (clipping vegetation) between 2015 and 2018 at two mountain rangeland sites: Spiti valley, in the Indian Trans-Himalaya and Tost, in the Gobi-Altai Mountains in Mongolia.

Clipping and climate change manipulations interactively reduced vegetation cover and biomass but did not affect species richness. Treatment effects and their interactions varied between sites. In ungrazed plots, vegetation cover and biomass declined sharply in response to warming (18\%-35\%) and drought (20\%-50\%) at the two sites, and, surprisingly also declined slightly in response to increased rainfall (20\%) at Tost. While the effects of climate treatments were largely similar in the grazed and ungrazed plots in Tost, they were larger in the ungrazed plots in Spiti. The decline in vegetation cover was driven by a decline in the cover of both forbs and grasses.

In combination, grazing and warming (Tost) or drought (Spiti) had sub-additive effects, that is, the decrease in vegetation cover in response to grazing and warming/drought was less than the sum of their independent effects but greater than the effect of either manipulation alone. Of the two, warming had a greater effect than drought at the more arid site (Tost), whereas drought had a larger effect at the more mesic site (Spiti).

Synthesis and applications. Our findings show that future changes in climate, including just over 1 degrees C of warming, could undermine the sustainability of pastoral economies and the persistence of wildlife across Asian montane rangelands. Furthermore, grazing by herbivores will play an important role in mediating rangeland responses to climate change; thus, pasture management in concert with local pastoralists will be crucial in mitigating the adverse effects of climate change on rangelands, pastoral livelihoods and wildlife populations.

}, doi = {10.1111/1365-2664.13781}, author = {Kohli, Mayank and Mijiddorj, Tserennadmid Nadia and Suryawanshi, Kulbhushansingh Ramesh and Mishra, Charudutt and Boldgiv, Bazartseren and Sankaran, Mahesh} } @article {84573, title = {Health Heatmap of India: An Open Data Platform.}, journal = {J Indian Inst Sci}, year = {2020}, month = {2020 Oct 18}, pages = {1-16}, abstract = {

Health Heatmap of India is an open data platform built for bringing together data from diverse sources and facilitating visualization, analysis, and insight building from such data. In this paper, we describe the context and need for such an open data platform and describe the technical aspects of building it. The beta site of the portal is available at https://healthheatmapindia.org.

}, issn = {0970-4140}, doi = {10.1007/s41745-020-00196-z}, author = {Dinesh, Akshay S and Mathur, Varnita and Ansil, B R and Chandru, Vijay and Chellam, Ravi and Vanak, Abi Tamim and Ramakrishnan, Uma and Rajagopal, Prabhakar} } @article {79735, title = {Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking.}, journal = {Traffic}, volume = {21}, year = {2020}, month = {2020 Aug}, pages = {522-533}, abstract = {

Phagocytosis is a complex cellular uptake process involving multiple distinct steps of cargo recognition, uptake, phagosome maturation and eventual phagolysosome resolution. Emerging literature shows that heterogeneity of phagocytosis at multiple steps at a single cell level influences the population outcome. However, the determinants of phagocytic heterogeneity are not clear. Here we show that the variance in the endocytic capacity of individual cells in a macrophage population determines subsequent phagocytic uptake and trafficking. Our results document the extensive heterogeneity in the endocytic uptake of individual macrophages, and show that cells with higher endocytic capacity preferentially phagocytose diverse cargo, including pathogenic Mycobacterium tuberculosis. Interestingly, M. tuberculosis infected cells sustain the higher endocytic capacity following infection. Modulating endocytic capacity by inhibiting endocytosis reduces phagocytic uptake. Differential uptake of M. tuberculosis into cells with different endocytic capacities correlates with the efficiency of phagocytic delivery to lysosomes, thus contributing further to phagocytic as well as mycobacterial heterogeneity. Thus, variance in endocytic capacity is a determinant of generating heterogeneity in phagocytosis at multiple steps.

}, issn = {1600-0854}, doi = {10.1111/tra.12752}, author = {Sachdeva, Kuldeep and Goel, Manisha and Sundaramurthy, Varadharajan} } @article {78101, title = {Homology modeling identifies crucial amino-acid residues that confer higher Na+ transport capacity of OcHKT1;5 from Oryza coarctata Roxb.}, journal = {Plant Cell Physiol}, year = {2020}, month = {2020 May 07}, abstract = {

HKT1;5 loci/alleles are important determinants of crop salinity tolerance. HKT1;5s encode plasmalemma-localized Na+-transporters, retrieving xylem Na+ into xylem parenchyma cells, reducing shoot Na+ accumulation. Allelic variation in rice OsHKT1;5 sequence in specific landraces (Nona Bokra OsHKT1;5-NB/Nipponbare OsHKT1;5-Ni) correlates with variation in salt tolerance. Oryza coarctata, a halophytic wild rice, grows in fluctuating salinity at the seawater-estuarine interface in Indian and Bangladeshi coastal regions. The distinct transport characteristics of the shoots and roots expressing O. coarctata OcHKT1;5 transporter, are reported vis-{\`a}-vis OsHKT1;5-Ni. Yeast sodium extrusion-deficient cells expressing\ OcHKT1;5 are sensitive to increasing Na+ (10-100 mM). Electrophysiological measurements in Xenopus oocytes expressing O. coarctata or rice HKT1;5 transporters indicates that OcHKT1;5, like OsHKT1;5-Ni is a Na+-selective transporter, but displays 16-fold lower affinity for Na+ and 3.5-fold higher maximal conductance than OsHKT1;5-Ni. For Na+ concentrations greater than 10 mM, OcHKT1;5 conductance is higher than that of OsHKT1;5-Ni, indicating potential of OcHKT1;5 for increasing domesticated rice salt tolerance. Homology modeling/ simulation suggests that four key amino acid changes in OcHKT1;5 (in loops on the extracellular side; E239K, G207R, G214R, L363V), account for its lower affinity and higher Na+ conductance vis-{\`a}-vis OsHKT1;5-Ni. Of these, E239K in OcHKT1;5, confers lower affinity for Na+ transport, as evidenced by Na+ transport assays of reciprocal site directed mutants for both transporters (OcHKT1;5- K239E, OsHKT1;5-Ni- E270K) in Xenopus oocytes. Both transporters have analogous roles in xylem sap desalinization and differences in Na+ transport affinity/ conductance between the transporters is attributable to differences in xylem sap Na+ concentrations in both species.

}, issn = {1471-9053}, doi = {10.1093/pcp/pcaa061}, author = {Somasundaram, Suji and V{\'e}ry, Anne-Ali{\'e}nor and Vinekar, Rithvik S and Ishikawa, Tetsuya and Kumari, Kumkum and Pulipati, Shalini and Kumaresan, Kavitha and Corratg{\'e}-Faillie, Claire and Sowdhamini, R and Parida, Ajay and Shabala, Lana and Shabala, Sergey and Venkataraman, Gayatri} } @article {73646, title = {How to halt the global decline of lands}, journal = {NATURE SUSTAINABILITY}, year = {2020}, month = {02/2020}, abstract = {

The assessment of land degradation and restoration by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services shows that land degradation across the globe is a wide and severe issue and is showing no signs of slowing down. This trend must be halted and reversed.

}, doi = {10.1038/s41893-020-0477-x}, author = {Willemen, Louise and Barger, Nichole N and ten Brink, Ben and Cantele, Matthew and Erasmus, Barend F. N and Fisher, Judith L. and Gardner, Toby and Holland, Timothy G. and Kohler, Florent and Kotiaho, Janne S and von Maltitz, Graham P and Nangendo, Grace and Pandit, Ram and Parrotta, John A and Potts, Matthew D and Prince, Stephen D and Sankaran, Mahesh and Brainich, Anastasia and Montanarella, Luca and Scholes, Robert} } @article {77440, title = {Human footprint differentially impacts genetic connectivity of four wide-ranging mammals in a fragmented landscape}, journal = {DIVERSITY AND DISTRIBUTIONS}, volume = {26}, year = {2020}, month = {03/2020}, pages = {299-314}, abstract = {

Aim: Maintaining connectivity is critical for long-term persistence of wild carnivores in landscapes fragmented due to anthropogenic activity. We examined spatial genetic structure and the impact of landscape features on genetic structure in four widespread species-jungle cat (Felis chaus), leopard (Panthera pardus), sloth bear (Melursus ursinus) and tiger (Panthera tigris).

Location: Our study was carried out in the central Indian landscape, a stronghold in terms of distribution and abundance of large mammals. The landscape comprises fragmented forests embedded in a heterogeneous matrix of multiple land use types.

Methods: Microsatellite data from non-invasively sampled individuals (90 jungle cats, 82 leopards, 104 sloth bears and 117 tigers) were used to investigate genetic differentiation. Impact of landscape features on genetic structure was inferred using a multimodel landscape resistance optimization approach.

Results: All four study species revealed significant isolation by distance (IBD). The correlation between genetic and geographic distance was significant only over a short distance for jungle cat, followed by longer distances for sloth bear, leopard and tiger. Overall, human footprint had a high negative impact on gene flow in tigers, followed by leopards, sloth bears and the least on jungle cats. Individual landscape variables-land use, human population density, density of linear features and roads-impacted the study species differently. Although land use was found to be an important variable explaining genetic structure for all four species, the amount of variation explained, and the optimum spatial resolution and the resistance values of different land use classes varied.

Main conclusions: As expected from theory, but rarely demonstrated using empirical data, the pattern of spatial autocorrelation of genetic variation scaled with dispersal ability and density of the study species. Landscape genetic analyses revealed species-specific impact of landscape features and provided insights into interactions between species biology and landscape structure. Our results emphasize the need for incorporating functional connectivity data from multiple species for landscape-level conservation planning.

}, doi = {10.1111/ddi.13022}, author = {Thatte, P and Chandramouli, A and Tyagi, A and Patel, K and Baro, P and Chhattani, H and Ramakrishnan, U} } @article {77379, title = {The hypertrophic cardiomyopathy mutations R403Q and R663H increase the number of myosin heads available to interact with actin.}, journal = {Sci Adv}, volume = {6}, year = {2020}, month = {2020 04}, pages = {eaax0069}, abstract = {

Hypertrophic cardiomyopathy (HCM) mutations in β-cardiac myosin and myosin binding protein-C (MyBP-C) lead to hypercontractility of the heart, an early hallmark of HCM. We show that hypercontractility caused by the HCM-causing mutation R663H cannot be explained by changes in fundamental myosin contractile parameters, much like the HCM-causing mutation R403Q. Using enzymatic assays with purified human β-cardiac myosin, we provide evidence that both mutations cause hypercontractility by increasing the number of functionally accessible myosin heads. We also demonstrate that the myosin mutation R403Q, but not R663H, ablates the binding of myosin with the C0-C7 fragment of MyBP-C. Furthermore, addition of C0-C7 decreases the wild-type myosin basal ATPase single turnover rate, while the mutants do not show a similar reduction. These data suggest that a primary mechanism of action for these mutations is to increase the number of myosin heads functionally available for interaction with actin, which could contribute to hypercontractility.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aax0069}, author = {Sarkar, Saswata S and Trivedi, Darshan V and Morck, Makenna M and Adhikari, Arjun S and Pasha, Shaik N and Ruppel, Kathleen M and Spudich, James A} } @article {78002, title = {Immediate early gene kakusei potentially plays a role in the daily foraging of honey bees.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0222256}, abstract = {

kakusei is a non-coding RNA that is overexpressed in foraging bee brain. This study describes a possible role of the IEG kakusei during the daily foraging of honey bees. kakusei was found to be transiently upregulated within two hours during rewarded foraging. Interestingly, during unrewarded foraging the gene was also found to be up-regulated, but immediately lowered when food was not rewarded. Moreover, the kakusei overexpression was diminished within a very short time when the time schedule of feeding was changed. This indicates the potential role of kakusei on the motivation of learned reward foraging. These results provide evidence for a dynamic role of kakusei during for aging of bees, and eventually its possible involvement in learning and memory. Thus the kakusei gene could be used as search tool in finding distinct molecular pathways that mediate diverse behavioral components of foraging.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0222256}, author = {Singh, Asem Surindro and Takhellambam, Machathoibi Chanu and Cappelletti, Pamela and Feligioni, Marco} } @article {86473, title = {Impact of Temperature and Time Interval Prior to Immature Testicular-Tissue Organotypic Culture on Cellular Niche.}, journal = {Reprod Sci}, year = {2020}, month = {2020 Dec 15}, abstract = {

Cryopreservation of immature-testicular-tissue (ITT) prior to gonadotoxic treatment, while experimental, is the only recommended option for fertility preservation in prepubertal boys. The handling and manipulation of ITT before cryopreservation could influence the functionality of cells during fertility restoration, which this study explored by evaluating cellular niche and quality of mouse ITT subjected to various temperatures and time durations in vitro. ITT from 6-day-old mice were handled at ultraprofound-hypothermic, profound-hypothermic, and mild-warm-ischemic temperatures for varying time periods prior to 14-day organotypic culture. Viability, functionality, synaptonemal complex and chromatin remodeling markers were assessed. Results have shown that cell viability, testosterone level, and in vitro proliferation ability did not change when ITT were held at ultraprofound-hypothermic-temperature up to 24\ h, whereas cell viability was significantly reduced (P \< 0.01), when held at profound-hypothermic-temperature for 24\ h before culture. Further, cell viability and testosterone levels in cultured cells from profound-hypothermic group were comparable to corresponding ultraprofound-hypothermic group but with moderate reduction in postmeiotic cells (P \< 0.01). In conclusion, holding ITT at ultraprofound-hypothermic-temperature is most suitable for organotypic culture, whereas short-term exposure at profound-hypothermic-temperature may compromise postmeiotic germ cell yield post in vitro culture. This data, albeit in mouse model, will have immense value in human prepubertal fertility restoration research.

}, issn = {1933-7205}, doi = {10.1007/s43032-020-00396-z}, author = {Salian, Sujith Raj and Pandya, Riddhi Kirit and Laxminarayana, Sindhura Lakshmi Koulmane and Krishnamurthy, Hanumantappa and Cheredath, Aswathi and Tholeti, Prathima and Uppangala, Shubhashree and Kalthur, Guruprasad and Majumdar, Subeer and Schlatt, Stefan and Adiga, Satish Kumar} } @article {78092, title = {In vitro human stem cell derived cultures to monitor calcium signaling in neuronal development and function}, journal = {Wellcome Open Res}, volume = {5}, year = {2020}, month = {2020}, pages = {16}, abstract = {

The development of the human brain involves multiple cellular processes including cell division, migration, and dendritic growth. These processes are triggered by developmental cues and lead to interactions of neurons and glial cells to derive the final complex organization of the brain. Developmental cues are transduced into cellular processes through the action of multiple intracellular second messengers including calcium. Calcium signals in cells are shaped by large number of proteins and mutations in several of these have been reported in human patients with brain disorders.\  However, the manner in which such mutations impact human brain development remains poorly understood. A key limitation in this regard is the need for a model system in which calcium signaling can be studied in neurons of patients with specific brain disorders. Here we describe a protocol to differentiate human neural stem cells into cortical neuronal networks that can be maintained as live cultures up to 120 days in a dish. Our protocol generates a 2D culture that exhibits molecular features of several layers of the human cerebral cortex. Using fluorescence imaging of intracellular calcium levels, we describe the development of neuronal activity as measured by intracellular calcium transients during development . These transients were dependent on the activity of voltage gated calcium channels and were abolished by blocking sodium channel activity. Using transcriptome analysis, we describe the full molecular composition of such cultures following differentiation thus offering an insight into the molecular basis of activity. Our approach will facilitate the understanding of calcium signaling defects during cortical neuron development in patients with specific brain disorders and a mechanistic analysis of these defects using genetic manipulations coupled with cell biological and physiological analysis.

}, issn = {2398-502X}, doi = {10.12688/wellcomeopenres.15626.1}, author = {Sharma, Yojet and Saha, Sankhanil and Joseph, Annu and Krishnan, Harini and Raghu, Padinjat} } @article {83644, title = {Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study.}, journal = {Molecules}, volume = {25}, year = {2020}, month = {2020 Oct 01}, abstract = {

This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO)-where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline-to two genotypically different breast cancer cells, MCF-7 (p53 and ER) and MDA-MB-231 (p53 and ER). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox-cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)-phenolate complex[Cu(tdp)(phen)] offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.

}, issn = {1420-3049}, doi = {10.3390/molecules25194504}, author = {Periasamy, Vaiyapuri Subbarayan and Riyasdeen, Anvarbatcha and Rajendiran, Venugopal and Palaniandavar, Mallayan and Krishnamurthy, Hanumanthappa and Alshatwi, Ali Abdullah and Akbarsha, Mohammad Abdulkader} } @article {81507, title = {Insect architecture: structural diversity and behavioral principles.}, journal = {Curr Opin Insect Sci}, year = {2020}, month = {2020 Aug 22}, abstract = {

Insects build myriad structures out of diverse materials. These structures serve purposes that range from facilitating prey capture to housing their entire colony. Whereas some insects operate solitarily, others collectively build large and complex structures. The architecture of these structures vis-{\`a}-vis their ultimate function poses fascinating questions that require multidisciplinary investigations. Importantly, because the underlying design and architectural principles have evolved over millions of years to withstand multitude of environmental perturbations, they offer important lessons for human-made structures. The vast variety of insect-built structures reflects how diverse insects have adapted to resolve the ecological challenges in their specific habitats. Here, we survey insect-built structures from a comparative perspective to ask what design and architectural principles can be gleaned from them. We discuss the key hypotheses about building-behaviours, their neural underpinnings, the functional role of insect-built structures and their biomimetic potential.

}, issn = {2214-5753}, doi = {10.1016/j.cois.2020.08.005}, author = {Sane, Sanjay P and Ramaswamy, Sree Subha and Raja, Sreekrishna Varma} } @article {59709, title = {Inter-individual variation in honey bee dance intensity correlates with expression of the foraging gene.}, journal = {Genes Brain Behav}, volume = {19}, year = {2020}, month = {19/Jan}, abstract = {

Individual behavioural differences in responding to the same stimuli is an integral part of division of labour in eusocial insect colonies. Among honey bee nectar foragers, individuals strongly differ in their sucrose responsiveness, which correlates with strong differences in behavioural decisions. In this study, we explored whether the mechanisms underlying the regulation of foraging are linked to inter-individual differences in the waggle dance activity of honey bee foragers. We first quantified the variation in dance activity amongst groups of foragers visiting an artificial feeder filled consecutively with different sucrose concentrations. We then determined for these foragers the sucrose responsiveness and the brain expression levels of three genes associated with food search and foraging; the foraging gene Amfor, octopamine receptor gene AmoctαR1 and insulin receptor AmInR-2. As expected, foragers showed large inter-individual differences in their dance activity, irrespective of the reward offered at the feeder. The sucrose responsiveness correlated positively with the intensity of the dance activity at the higher reward condition, with the more responsive foragers having a higher intensity of dancing. Out of the three genes tested, Amfor expression significantly correlated with dance activity, with more active dancers having lower expression levels. Our results show that dance and foraging behaviour in honey bees have similar mechanistic underpinnings and supports the hypothesis that the social communication behaviour of honey bees might have evolved by co-opting behavioural modules involved in food search and foraging in solitary insects.

}, issn = {1601-183X}, doi = {10.1111/gbb.12592}, author = {George, Ebi Antony and Br{\"o}ger, Ann-Kathrin and Thamm, Markus and Brockmann, Axel and Scheiner, Ricarda} } @article {87006, title = {The Interplay of Host Lysosomes and Intracellular Pathogens. }, journal = {Front Cell Infect Microbiol}, year = {2020}, month = {11/2020}, abstract = {

Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as Mycobacterium tuberculosis (Mtb) and Salmonella avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking. In this review, the mechanisms by which the respective pathogen containing vacuoles (PCVs) intersect with lysosomal trafficking pathways and maintain their distinctness are discussed. Despite such active inhibition of lysosomal targeting, emerging literature shows that different pathogens or pathogen derived products exhibit a global influence on the host lysosomal system. Pathogen mediated lysosomal enrichment promotes the trafficking of a sub-set of pathogens to lysosomes, indicating heterogeneity in the host-pathogen encounter. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. The review also briefly discusses the heterogeneity in the lysosomal targeting of these pathogens and the possible mechanisms and consequences.

}, doi = {0.3389/fcimb.2020.595502}, author = {Sachdeva, K and Sundaramurthy, V} } @article {83641, title = {A knowledge-driven protocol for prediction of proteins of interest with an emphasis on biosynthetic pathways.}, journal = {MethodsX}, volume = {7}, year = {2020}, month = {2020}, pages = {101053}, abstract = {

This protocol describes a stepwise process to identify proteins of interest from a query proteome derived from NGS data. We implemented this protocol on transcriptome to identify proteins involved in secondary metabolite and vitamin biosynthesis and ion transport. This knowledge-driven protocol identifies proteins using an integrated approach involving sensitive sequence search and evolutionary relationships. We make use of functionally important residues (FIR) specific for the query protein family identified through its homologous sequences and literature. We screen protein hits based on the clustering with true homologues through phylogenetic tree reconstruction complemented with the FIR mapping. The protocol was validated for the protein hits through qRT-PCR and transcriptome quantification. Our protocol demonstrated a higher specificity as compared to other methods, particularly in distinguishing cross-family hits. This protocol was effective in transcriptome data analysis of as described in Pasha et al.{\textbullet}Knowledge-driven protocol to identify secondary metabolite synthesizing protein in a highly specific manner.{\textbullet}Use of functionally important residues for screening of true hits.{\textbullet}Beneficial for metabolite pathway reconstruction in any (species, metagenomics) NGS data.

}, issn = {2215-0161}, doi = {10.1016/j.mex.2020.101053}, author = {Joshi, Adwait G and Harini, K and Meenakshi, Iyer and Shafi, K Mohamed and Pasha, Shaik Naseer and Mahita, Jarjapu and Sajeevan, Radha Sivarajan and Karpe, Snehal D and Ghosh, Pritha and Nitish, Sathyanarayanan and Gandhimathi, A and Mathew, Oommen K and Prasanna, Subramanian Hari and Malini, Manoharan and Mutt, Eshita and Naika, Mahantesha and Ravooru, Nithin and Rao, Rajas M and Shingate, Prashant N and Sukhwal, Anshul and Sunitha, Margaret S and Upadhyay, Atul K and Vinekar, Rithvik S and Sowdhamini, Ramanathan} } @article {73644, title = {Laboratory Evolution Experiments Help Identify a Predominant Region of Constitutive Stable DNA Replication Initiation.}, journal = {mSphere}, volume = {5}, year = {2020}, month = {2020 Feb 26}, abstract = {

The bacterium can initiate replication in the absence of the replication initiator protein DnaA and/or the canonical origin of replication in a background. This phenomenon, which can be primed by R-loops, is called constitutive stable DNA replication (cSDR). Whether DNA replication during cSDR initiates in a stochastic manner through the length of the chromosome or at specific sites and how can find adaptations to loss of fitness caused by cSDR remain inadequately answered. We use laboratory evolution experiments of strains followed by deep sequencing to show that DNA replication preferentially initiates within a broad region located \~{}0.4 to 0.7 Mb clockwise of This region includes many bisulfite-sensitive sites, which have been previously defined as R-loop-forming regions, and includes a site containing sequence motifs that favor R-loop formation. Initiation from this region would result in head-on replication-transcription conflicts at rRNA loci. Inversions of these rRNA loci, which can partly resolve these conflicts, help the bacterium suppress the fitness defects of cSDR. These inversions partially restore the gene expression changes brought about by cSDR. The inversion, however, increases the possibility of conflicts at essential mRNA genes, which would utilize only a minuscule fraction of RNA polymerase molecules, most of which transcribe rRNA genes. Whether subsequent adaptive strategies would attempt to resolve these conflicts remains an open question. The bacterium can replicate its DNA even in the absence of the molecules that are required for canonical replication initiation. This often requires the formation of RNA-DNA hybrid structures and is referred to as constitutive stable DNA replication (cSDR). Where on the chromosome does cSDR initiate? We answer this question using laboratory evolution experiments and genomics and show that selection favors cSDR initiation predominantly at a region \~{}0.6 Mb clockwise of Initiation from this site will result in more head-on collisions of DNA polymerase with RNA polymerase operating on rRNA loci. The bacterium adapts to this problem by inverting a region of the genome including several rRNA loci such that head-on collisions between the two polymerases are minimized. Understanding such evolutionary strategies in the context of cSDR can provide insights into the potential causes of resistance to antibiotics that target initiation of DNA replication.

}, issn = {2379-5042}, doi = {10.1128/mSphere.00939-19}, author = {Veetil, Reshma T and Malhotra, Nitish and Dubey, Akshara and Seshasayee, Aswin Sai Narain} } @article {84067, title = {Large geographic variability in the resistance of corals to thermal stress}, journal = {Global Ecology and Biogeography}, year = {2020}, month = {10/2020}, abstract = {

Predictions for the future of coral reefs are largely based on thermal exposure and poorly account for potential geographic variation in biological sensitivity to thermal stress. Without accounting for complex sensitivity responses, simple climate exposure models and associated predictions may lead to poor estimates of future coral survival and lead to policies that fail to identify and implement the most appropriate interventions. To begin filling this gap, we evaluated a number of attributes of coral taxa and communities that are predicted to influence coral resistance to thermal stress over a large geographic range.

}, doi = {10.1111/geb.13191}, author = {McClanahan, Tim R and Maina, Joseph M and Darling, Emily S and Guillaume, Mireille M and Muthiga, Nyawira and D{\textquoteright}agata, Stephanie and Leblond, Julien and Arthur, Rohan and Jupiter, Stacy D and Wilson, Shaun and Mangubhai, Sangeeta and Ussi, Ali M and Humphries, Austin T and Patankar, Vardhan and Shedrawi, George and Julius, Pagu and Ndagala, January and Grimsditch, Gabriel} } @article {71098, title = {Ligand dependent gene regulation by transient ERα clustered enhancers.}, journal = {PLoS Genet}, volume = {16}, year = {2020}, month = {2020 Jan 06}, pages = {e1008516}, abstract = {

Unliganded Estrogen receptor alpha (ERα) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, or persistent, ERα-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERα-bound sites, forming Ligand Dependent ERα Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERα condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish, at TFF1 and NRIP1 locus, a direct link between ERα condensates, ERα enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1008516}, author = {Saravanan, Bharath and Soota, Deepanshu and Islam, Zubairul and Majumdar, Sudeshna and Mann, Rajat and Meel, Sweety and Farooq, Umer and Walavalkar, Kaivalya and Gayen, Srimonta and Singh, Anurag Kumar and Hannenhalli, Sridhar and Notani, Dimple} } @article {78099, title = {Lithium response in bipolar disorder correlates with improved cell viability of patient derived cell lines.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {2020 May 04}, pages = {7428}, abstract = {

Lithium is an effective, well-established treatment for bipolar disorder (BD). However, the mechanisms of its action, and reasons for variations in clinical response, are unclear. We used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs), from BD patients characterized for clinical response to lithium (using the "Alda scale" and "NIMH Retrospective Life chart method"), to interrogate cellular phenotypes related to both disease and clinical lithium response. NPCs from two biologically related BD patients who differed in their clinical response to lithium were compared with healthy controls. RNA-Seq and analysis, mitochondrial membrane potential (MMP), cell viability, and cell proliferation parameters were assessed, with and without in vitro lithium. These parameters were also examined in LCLs from 25 BD patients (16 lithium responders and 9 non-responders), and 12 controls. MMP was lower in both NPCs and LCLs from BD; but it was reversed with in vitro lithium only in LCLs, and this was unrelated to clinical lithium response. The higher cell proliferation observed in BD was unaffected by in vitro lithium. Cell death was greater in BD. However, LCLs from clinical lithium responders could be rescued by addition of in vitro lithium. In vitro lithium also enhanced BCL2 and GSK3B expression in these cells. Our findings indicate cellular phenotypes related to the disease (MMP, cell proliferation) in both NPCs and LCLs; and those related to clinical lithium response (cell viability, BCL2/GSK3B expression) in LCLs.

}, issn = {2045-2322}, doi = {10.1038/s41598-020-64202-1}, author = {Paul, Pradip and Iyer, Shruti and Nadella, Ravi Kumar and Nayak, Rashmitha and Chellappa, Anirudh S and Ambardar, Sheetal and Sud, Reeteka and Sukumaran, Salil K and Purushottam, Meera and Jain, Sanjeev and Viswanath, Biju} } @article {74442, title = {Loss of function of Oryza sativa Argonaute 18 induces male sterility and reduction in phased small RNAs.}, journal = {Plant Reprod}, volume = {33}, year = {2020}, month = {2020 Mar}, pages = {59-73}, abstract = {

KEY MESSAGE: In this manuscript, we show that Oryza sativa indica Argonaute protein AGO18 is required for male gametophyte development likely to through a small RNA-mediated mechanism. Monocots have evolved unique gene silencing pathways due to the presence of unique members of Dicer-like and Argonaute (AGO) family members. Among the monocot AGO homologs, AGO18 occupies a unique position. Previous reports have implicated this protein in viral resistance as well as in gametogenesis, likely through its competition with AGO1 clade members for micro(mi)RNAs and other small (s)RNAs. Although expression of rice AGO18 in specific stages of male gametogenesis has been documented, its major functions in plant development remain poorly understood. Here, we show that Oryza sativa indica AGO18 is involved in male gametophyte development. Knockdown (KD) of AGO18 in transgenic rice lines resulted in stunted plants that are male sterile, whereas their carpels were functional. Transcriptome analysis revealed downregulation of several pollen development-associated genes in KD lines. sRNA sequencing in vegetative and reproductive tissues of KD lines indicated reduction of miRNAs and phased secondary sRNAs implicated in male gametophyte development. Our results indicate a distinct role for rice AGO18 in male fertility.

}, issn = {2194-7961}, doi = {10.1007/s00497-020-00386-w}, author = {Das, Soumita and Swetha, Chenna and Pachamuthu, Kannan and Nair, Ashwin and Shivaprasad, P V} } @article {86828, title = {Mammals Make Use of Cashew Plantations in a Mixed Forest-Cashew Landscape}, journal = {FRONTIERS IN ENVIRONMENTAL SCIENCE}, volume = {8}, year = {2020}, month = {11/2020}, abstract = {

Heterogeneous landscapes harboring mosaics of natural habitat and agriculture are increasingly gaining conservation focus in the tropics. While research on cash crops such as coffee, rubber, and oil palm has led to an understanding of their role as supplementary habitats, such has remained limited in cashew plantations despite it being a cash crop of global significance. We conducted a study to understand the occurrence of terrestrial mammal species in a mixed forest-cashew landscape in the northern Western Ghats, India. During January to April 2016, we used trail cameras to sample a total area of 25 km(2) divided into 100 grid cells of 0.25 km(2) each. We deployed six trail cameras for a 24 h period in each grid cell and obtained photo-captures of 11 species in forests, of which nine were detected in cashew plantations, but most species showed low capture rates. For three of these species-Indian crested porcupine, sambar, and wild pig-we modeled habitat use as a function of site-specific attributes. Wild pig showed a higher probability of use of cashew than forest, while porcupine and sambar did not show any pronounced differences between the two land uses. The probability of habitat use by sambar and porcupine was positively influenced by undergrowth but not for the wild pig. Wild pig habitat use was positively related to increased proximity of human settlements and increasing distance to forests, but the pattern was unreliable for sambar and porcupine. Our preliminary study demonstrates that a subset of terrestrial mammals in the forest makes use of cashew plantations and highlights the need for further research in forest-cashew landscapes to assess conservation opportunities.

}, doi = {10.3389/fenvs.2020.556942}, author = {Rege, Anushka and Punjabi, Girish Arjun and Jathanna, Devcharan and Kumar, Ajith} } @article {85901, title = {Measurement of Alcohol-Dependent Physiological Changes in Red Blood Cells Using Resistive Pulse Sensing.}, journal = {ACS Sens}, year = {2020}, month = {2020 Nov 18}, abstract = {

Alcohol exposure has been postulated to adversely affect the physiology and function of the red blood cells (RBCs). The global pervasiveness of alcohol abuse, causing health issues and social problems, makes it imperative to resolve the physiological effects of alcohol on RBC physiology. Alcohol consumed recreationally or otherwise almost immediately alters cell physiology in ways that is subtle and still unresolved. In this paper, we introduce a high-resolution device for quantitative electrofluidic measurement of changes in RBC volume upon alcohol exposure. We present an exhaustive calibration of our device using model cells to measure and resolve volume changes down to 0.6 fL. We find an RBC shrinkage of 5.3\% at 0.125\% ethanol (the legal limit in the United States) and a shrinkage of 18.5\% at 0.5\% ethanol (the lethal limit) exposure. Further, we also measure the time dependence of cell volume shrinkage (upon alcohol exposure) and then recovery (upon alcohol removal) to quantify shrinkage and recovery of RBC volumes. This work presents the first direct quantification of temporal and concentration-dependent changes in red blood cell volume upon ethanol exposure. Our device presents a universally applicable high-resolution and high-throughput platform to measure changes in cell physiology under native and diseased conditions.

}, issn = {2379-3694}, doi = {10.1021/acssensors.0c01302}, author = {Kaushik, Saurabh and Mahadeva, Manohara and Sundaramurthy, Varadharajan and Soni, Gautam Vivek} } @article {77391, title = {Mechanism of CcdA-Mediated Rejuvenation of DNA Gyrase.}, journal = {Structure}, volume = {28}, year = {2020}, month = {2020 May 05}, pages = {562-572.e4}, abstract = {

Most biological processes involve formation of transient complexes where binding of a ligand allosterically modulates function. The ccd toxin-antitoxin system is involved in plasmid maintenance and bacterial persistence. The CcdA antitoxin accelerates dissociation of CcdB from its complex with DNA gyrase, binds and neutralizes CcdB, but the\ mechanistic details are unclear. Using a series of experimental and\ computational approaches, we\ demonstrate the\ formation of transient ternary and quaternary CcdA:CcdB:gyrase complexes and\ delineate the molecular steps involved in the rejuvenation process. Binding of region 61-72 of CcdA to CcdB induces the vital structural and dynamic changes required to facilitate dissociation from gyrase, region 50-60 enhances the dissociation process through additional allosteric effects, and segment 37-49 prevents gyrase rebinding. This study provides insights into molecular mechanisms responsible for recovery of\ CcdB-poisoned cells from a persister-like state. Similar methodology can be used to characterize other important transient, macromolecular complexes.

}, issn = {1878-4186}, doi = {10.1016/j.str.2020.03.006}, author = {Aghera, Nilesh K and Prabha, Jyothi and Tandon, Himani and Chattopadhyay, Gopinath and Vishwanath, Sneha and Srinivasan, Narayanaswamy and Varadarajan, Raghavan} } @article {77446, title = {Mechanistic Insights into an Unusual Side-Chain-Mediated N-C Bond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin.}, journal = {J Am Soc Mass Spectrom}, volume = {31}, year = {2020}, month = {2020 May 06}, pages = {1083-1092}, abstract = {

Conopressin, a nonapeptide disulfide CFIRNCPKG amide present in cone snail venom, undergoes a facile cleavage at the Cys6-Pro7 peptide bond to yield a disulfide bridged ion. Analysis of the mass spectral fragmentation pattern reveals the presence of a major fragment ion, which is unambiguously assigned as the tripeptide sequence IRN amide. The sequence dependence of this unusual fragmentation process has been investigated by comparing it with the fragmentation patterns of related peptides, oxytocin (CYIQNCPLG amide), Lys-vasopressin (CYFQNCPKG amide), and a series of synthetic analogues. The results establish the role of the Arg4 residue in facilitating the unusual N-C bond cleavage at Cys6. Structures are proposed for a modified disulfide bridged fragment containing the Cys1 and Cys6 residues. Gas-phase molecular dynamics simulations provide evidence for the occurrence of conformational states that permit close approach of the Arg4 side chain to the Cys6 C methylene protons.

}, issn = {1879-1123}, doi = {10.1021/jasms.0c00023}, author = {Kumar, Sanjeev and Venkatesha, M Achanna and Lall, Sahil and Prakash, Sunita and Balaram, Padmanabhan} } @article {82354, title = {Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Integration Sites and Involvement of the KMT2D Tumor Suppressor Gene.}, journal = {Viruses}, volume = {12}, year = {2020}, month = {2020 Aug 31}, abstract = {

Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCPyV) or UV-linked mutations. MCPyV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCPyV large T antigen replication incompetent. We used the open access HPV Detector/Cancer-virus Detector tool to determine MCPyV integration sites in whole-exome sequencing data from five MCC cases, thereby adding to the limited published MCPyV integration site junction data. We also systematically reviewed published data on integration for MCPyV in the human genome, presenting a collation of 123 MCC cases and their linked chromosomal sites. We confirmed that there were no highly recurrent specific sites of integration. We found that chromosome 5 was most frequently involved in MCPyV integration and that integration sites were significantly enriched for genes with binding sites for oncogenic transcription factors such as LEF1 and ZEB1, suggesting the possibility of increased open chromatin in these gene sets. Additionally, in one case we found, for the first time, integration involving the tumor suppressor gene , adding to previous reports of rare MCPyV integration into host tumor suppressor genes in MCC.

}, issn = {1999-4915}, doi = {10.3390/v12090966}, author = {Arora, Reety and Choi, Jae Eun and Harms, Paul W and Chandrani, Pratik} } @article {83633, title = {Metabarcoding for parallel identification of species, sex and diet of obligate scavengers: an application to globally-threatened Gyps vultures}, journal = {CONSERVATION GENETICS RESOURCES}, year = {2020}, month = {2020}, abstract = {

After suffering a massive decline (similar to 99\%) in numbers caused by feeding on livestock carcasses containing the nephrotoxic drug diclofenac, critically endangeredGypsvultures now persist in low numbers in the Indian subcontinent. Most are concentrated near National Parks, likely due to availability of wild carcasses free from toxic veterinary drugs. Quantification of vulture diets is critical to test this hypothesis. We describe a validated "field-to-benchtop-to-desktop" metabarcoding workflow for assessing species- and sex-specific diet of these obligate scavengers from non-invasively collected faecal samples. Seven metabarcodes were designed to simultaneouslsy identify the vulture species, sex and diet. Amplicons generated from multiplex PCRs were indexed and sequenced on an Illumina Miseq platform. We included controls and three replicates per sample to establish a series of non-arbitrary thresholds to filter the sequence data and eliminate cross-contamination, PCR/sequencing errors and false positives. This strategy enabled identification of species and sex for all samples and diet-specific sequences with high taxonomic resolution for 97\% of samples. Just four (two for diet, one each for vulture species and sexing) metabarcodes were sufficient to meet the objectives. This preliminary analysis suggests that domestic livestock is the most frequently consumed diet item across samples from inside and outside protected habitats. Our method provides a rapid and reliable tool for describing large-scale variation in consumption of domestic versus wild species in the diet of these scavengers, paving the way for a better understanding of the role protected areas play in persistence and recovery of the remainingGypsvultures in the wild.

}, doi = {10.1007/s12686-020-01171-7}, author = {Ghosh-Harihar, Mousumi and Gurung, Nehal and Shukla, Harsh and Sinha, Ishani and Pandit, Awadhesh and Prakash, Vibhu and Green, Rhys E. and Ramakrishnan, Uma} } @article {73643, title = {Mixed company: a framework for understanding the composition and organization of mixed-species animal groups.}, journal = {Biol Rev Camb Philos Soc}, year = {2020}, month = {2020 Feb 25}, abstract = {

Mixed-species animal groups (MSGs) are widely acknowledged to increase predator avoidance and foraging efficiency, among other benefits, and thereby increase participants{\textquoteright} fitness. Diversity in MSG composition ranges from two to 70 species of very similar or completely different phenotypes. Yet consistency in organization is also observable in that one or a few species usually have disproportionate importance for MSG formation and/or maintenance. We propose a two-dimensional framework for understanding this diversity and consistency, concentrating on the types of interactions possible between two individuals, usually of different species. One axis represents the similarity of benefit types traded between the individuals, while the second axis expresses asymmetry in the relative amount of benefits/costs accrued. Considering benefit types, one extreme represents the case of single-species groups wherein all individuals obtain the same supplementary, group-size-related benefits, and the other extreme comprises associations of very different, but complementary species (e.g. one partner creates access to food while the other provides vigilance). The relevance of social information and the matching of activities (e.g. speed of movement) are highest for relationships on the supplementary side of this axis, but so is competition; relationships between species will occur at points along this gradient where the benefits outweigh the costs. Considering benefit amounts given or received, extreme asymmetry occurs when one species is exclusively a benefit provider and the other a benefit user. Within this parameter space, some MSG systems are constrained to one kind of interaction, such as shoals of fish of similar species or leader-follower interactions in fish and other taxa. Other MSGs, such as terrestrial bird flocks, can simultaneously include a variety of supplementary and complementary interactions. We review the benefits that species obtain across the diversity of MSG types, and argue that the degree and nature of asymmetry between benefit providers and users should be measured and not just assumed. We then discuss evolutionary shifts in MSG types, focusing on drivers towards similarity in group composition, and selection on benefit providers to enhance the benefits they can receive from other species. Finally, we conclude by considering how individual and collective behaviour in MSGs may influence both the structure and processes of communities.

}, issn = {1469-185X}, doi = {10.1111/brv.12591}, author = {Goodale, Eben and Sridhar, Hari and Sieving, Kathryn E and Bangal, Priti and Colorado Z, Gabriel J and Farine, Damien R and Heymann, Eckhard W and Jones, Harrison H and Krams, Indrikis and Mart{\'\i}nez, Ari E and Monta{\~n}o-Centellas, Flavia and Mu{\~n}oz, Jenny and Srinivasan, Umesh and Theo, Anne and Shanker, Kartik} } @article {84948, title = {Modulation of flight and feeding behaviours requires presynaptic IPRs in dopaminergic neurons.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Nov 06}, abstract = {

Innate behaviours, although robust and hard wired, rely on modulation of neuronal circuits, for eliciting an appropriate response according to internal states and external cues. flight is one such innate behaviour that is modulated by intracellular calcium release through inositol 1,4,5-trisphosphate receptors (IPRs). Cellular mechanism(s) by which IPRs modulate neuronal function for specific behaviours remain speculative, in vertebrates and invertebrates. To address this, we generated an inducible dominant negative form of the IPR (IPR). Flies with neuronal expression of IPR exhibit flight deficits. Expression of IPR helped identify key flight-modulating dopaminergic neurons with axonal projections in the mushroom body. Flies with attenuated IPRs in these presynaptic dopaminergic neurons exhibit shortened flight bouts and a disinterest in seeking food, accompanied by reduced excitability and dopamine release upon cholinergic stimulation. Our findings suggest that the same neural circuit modulates the drive for food search and for undertaking longer flight bouts.

}, issn = {2050-084X}, doi = {10.7554/eLife.62297}, author = {Sharma, Anamika and Hasan, Gaiti} } @article {78005, title = {Modulation of β-catenin levels regulates cranial neural crest patterning and dispersal into first pharyngeal arch.}, journal = {Dev Dyn}, year = {2020}, month = {2020 May 19}, abstract = {

BACKGROUND: Vertebrate cranial neural crest cells (CNCCs) are multipotent, proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined.

RESULTS: Here, we report that a novel β-catenin-dependent regulation of N-Cadherin levels may drive CNCC patterning. In mouse embryos, at the first pharyngeal arch axial level, membrane β-catenin levels correlate with the extent of N-cadherin-mediated adhesion and thus suggest the presence of collective and dispersed states of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for regulating N-cadherin levels and cell-cell adhesion. Similarly, in β-catenin gain-of-function mutant mouse embryos, CNCC fail to lower N-cadherin levels. This indicates a failure to reduce cell-cell adhesion, which may underlie the failure of mutant CNCC to populate first pharyngeal arch.

CONCLUSION: We suggest that β-catenin-mediated regulation of CNCC adhesion, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.

}, issn = {1097-0177}, doi = {10.1002/dvdy.208}, author = {Javali, Alok and Lakshmanan, Vairavan and Palakodeti, Dasaradhi and Sambasivan, Ramkumar} } @article {86450, title = {Molecular and functional characterization of buffalo nasal epithelial odorant binding proteins and their structural insights by in silico and biochemical approaches}, journal = {J Biomol Struct Dyn}, year = {2020}, month = {12/2020}, pages = {1-24}, abstract = {

The olfactory system is capable of detecting and distinguishing thousands of environmental odorants that play a key role in reproduction, social behaviours including pheromones influenced classical events. Membrane secretary odorant binding proteins (OBPs) are soluble lipocalins, localized in the nasal membrane of mammals. They bind and carry odorants within the nasal epithelium to putative olfactory transmembrane receptors (ORs). OBP has not yet been exploited to develop a suitable technique to detect oestrus which is being reported as a difficult task in buffalo. In the present study, using molecular biology and protein engineering approaches, we have cloned six novel OBP isoforms from buffalo nasal epithelium odorant-binding proteins (bnOBPs). Furthermore, 3 D models were developed and molecular-docking, dynamics experiments were performed by in silico approaches. In particular, we found four residues (Phe104, Phe134, Phe69 and Asn118) in OBP1a, which contributed to favourable interactions towards two sex pheromones, specifically oleic acid and p-cresol. We expressed this protein in Escherichia coli from female buffalo urine and validated through fluorescence quenching studies to show similar strong binding affinities of OBP1a to oleic acid and p-cresol. By using structural data, the binding specificity was also verified by site-directed mutagenesis of the four residues followed by in vitro binding assays. Our results enable us to better understand the functions of different nasal epithelium OBP isoforms in buffaloes. They also lead to improved understanding of the interaction between olfactory proteins and odorants to develop highly selective biosensing devices for non-invasive detection of oestrus in buffaloes. Communicated by Ramaswamy H. Sarma.

}, doi = {10.1080/07391102.2020.1854117}, author = {Manikkaraja, C and Bhavika, M and Singh, R and Nagarathnam, B and George, G and Gulyani, A and Archunan, G and Sowdhamini, R} } @article {81498, title = {Molecular Evolution and Developmental Expression of Melanin Pathway Genes in Lepidoptera}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, volume = {8}, year = {2020}, month = {07/2020}, abstract = {

Pigmentation is involved in a wide array of biological functions across insect orders, including body patterning, thermoregulation, and immunity. The melanin pathway, in particular, has been characterized in several species. However, molecular evolution of the genes involved in this pathway is poorly explored. We traced the molecular evolution of six melanin pathway genes in 53 species of Lepidoptera covering butterflies and moths, and representing over 100 million years of diversification. We compared the rates of synonymous and non-synonymous substitutions within and between these genes to study the signatures of selection at the level of individual sites, genes, and branches of the gene tree. We found that molecular evolution of all six genes was governed by strong purifying selection. Yet, a number of sites showed signs of being under positive selection, including in the highly conserved domain regions of three genes. Further, we traced the expression of these genes across developmental stages, tissues, and sexes in thePapilio polytesbutterfly using a developmental transcriptome dataset. We observed that the expression patterns of the genes inP. polyteslargely reflected their known tissue-specific function in other species. The expression of sequentially acting genes in the melanin pathway was correlated. Interestingly, melanin pathway genes also showed a sexually dimorphic pattern of developmental heterochrony, i.e., females showed prominent upregulation of melanin pathway genes in pre-pupal stage compared to males, while males showed prominent upregulation in 9-day pupal wings compared to females. Our evolutionary and developmental analyses suggest that the vast diversity of wing patterning and pigmentation in Lepidoptera may have evolved despite largely constrained sequence evolution, with potential contribution from differential developmental expression of genes in a highly conserved pathway.

}, doi = {10.3389/fevo.2020.00226}, author = {Kuwalekar, Muktai and Deshmukh, Riddhi and Padvi, Ajay and Kunte, Krushnamegh} } @article {78107, title = {Monitoring protein ubiquitination and SUMOylation in real-time by NMR.}, journal = {Chem Commun (Camb)}, volume = {56}, year = {2020}, month = {2020 Jun 18}, pages = {6735-6738}, abstract = {

The covalent conjugation of ubiquitin (Ub), known as ubiquitination, is a multi-step reaction involving multiple enzymes. We report a real-time, tag-free method to monitor protein ubiquitination by NMR spectroscopy under physiological conditions. The approach is also applicable for monitoring other ubiquitin-like modifications, and the disassembly of Ub polymers.

}, issn = {1364-548X}, doi = {10.1039/d0cc02252g}, author = {Habibullah, Batul Ismail and Tripathi, Vasvi and Surana, Parag and Das, Ranabir} } @article {78164, title = {More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis.}, journal = {Chem Senses}, year = {2020}, month = {2020 Jun 20}, abstract = {

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change {\textpm}100) revealed a mean reduction of smell (-79.7 {\textpm} 28.7, mean {\textpm} SD), taste (-69.0 {\textpm} 32.6), and chemesthetic (-37.3 {\textpm} 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.

}, issn = {1464-3553}, doi = {10.1093/chemse/bjaa041}, author = {Parma, Valentina and Ohla, Kathrin and Veldhuizen, Maria G and Niv, Masha Y and Kelly, Christine E and Bakke, Alyssa J and Cooper, Keiland W and Bouysset, C{\'e}dric and Pirastu, Nicola and Dibattista, Michele and Kaur, Rishemjit and Liuzza, Marco Tullio and Pepino, Marta Y and Sch{\"o}pf, Veronika and Pereda-Loth, Veronica and Olsson, Shannon B and Gerkin, Richard C and Rohlfs Dom{\'\i}nguez, Paloma and Albayay, Javier and Farruggia, Michael C and Bhutani, Surabhi and Fjaeldstad, Alexander W and Kumar, Ritesh and Menini, Anna and Bensafi, Moustafa and Sandell, Mari and Konstantinidis, Iordanis and Di Pizio, Antonella and Genovese, Federica and {\"O}zt{\"u}rk, Lina and Thomas-Danguin, Thierry and Frasnelli, Johannes and Boesveldt, Sanne and Saatci, {\"O}zlem and Saraiva, Luis R and Lin, Cailu and Golebiowski, J{\'e}r{\^o}me and Dar Hwang, Liang- and Ozdener, Mehmet Hakan and Gu{\`a}rdia, Maria Dolors and Laudamiel, Christophe and Ritchie, Marina and Havl{\'\i}cek, Jan and Pierron, Denis and Roura, Eugeni and Navarro, Marta and Nolden, Alissa A and Lim, Juyun and Whitcroft, K L and Colquitt, Lauren R and Ferdenzi, Camille and Brindha, Evelyn V and Altundag, Aytug and Macchi, Alberto and Nunez-Parra, Alexia and Patel, Zara M and Fiorucci, S{\'e}bastien and Philpott, Carl M and Smith, Barry C and Lundstr{\"o}m, Johan N and Mucignat, Carla and Parker, Jane K and van den Brink, Mirjam and Schmuker, Michael and Fischmeister, Florian Ph S and Heinbockel, Thomas and Shields, Vonnie D C and Faraji, Farhoud and Santamar{\'\i}a, Enrique and Fredborg, William E A and Morini, Gabriella and Olofsson, Jonas K and Jalessi, Maryam and Karni, Noam and D{\textquoteright}Errico, Anna and Alizadeh, Rafieh and Pellegrino, Robert and Meyer, Pablo and Huart, Caroline and Chen, Ben and Soler, Graciela M and Alwashahi, Mohammed K and Welge-L{\"u}ssen, Antje and Freiherr, Jessica and de Groot, Jasper H B and Klein, Hadar and Okamoto, Masako and Singh, Preet Bano and Hsieh, Julien W and Reed, Danielle R and Hummel, Thomas and Munger, Steven D and Hayes, John E} } @article {82355, title = {Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in Drosophila tracheoblasts.}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Sep 02}, abstract = {

Larval tracheae of Drosophila harbour progenitors of the adult tracheal system (tracheoblasts). Thoracic tracheoblasts are arrested in the G2 phase of the cell cycle in an ATR (mei-41)-Checkpoint Kinase1 (grapes, Chk1) dependent manner prior to mitotic re-entry. Here we investigate developmental regulation of Chk1 activation. We report that Wnt signaling is high in tracheoblasts and this is necessary for high levels of activated (phosphorylated) Chk1. We find that canonical Wnt signaling facilitates this by transcriptional upregulation of Chk1 expression in cells that have ATR kinase activity. Wnt signalling is dependent on four Wnts (Wg, Wnt5, 6,10) that are expressed at high levels in arrested tracheoblasts and are downregulated at mitotic re-entry. Interestingly, none of the Wnts are dispensable and act synergistically to induce Chk1. Finally, we show that downregulation of Wnt signalling and Chk1 expression leads to mitotic re-entry and the concomitant upregulation of Dpp signalling, driving tracheoblast proliferation.

}, issn = {2050-084X}, doi = {10.7554/eLife.57056}, author = {Kizhedathu, Amrutha and Kunnappallil, Rose Sebastian and Bagul, Archit V and Verma, Puja and Guha, Arjun} } @article {78171, title = {A Mutant RNA Polymerase Activates the General Stress Response, Enabling Escherichia coli Adaptation to Late Prolonged Stationary Phase}, journal = {mSphere}, volume = {5}, year = {2020}, month = {04/2020}, abstract = {

Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony phenotype and slow growth and was able to outcompete its ancestor over a narrow time window in stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously exposed to the antibiotic. We show that an RpoC(A494V) mutation confers the slow growth and small colony phenotype on this variant. The ability of this mutation to confer a growth advantage in stationary phase depends on the availability of the stationary-phase sigma factor σS The RpoC(A494V) mutation upregulates the σS regulon. As shown over 20 years ago, early in prolonged stationary phase, σS attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance σS activity, either by mutating the gene for σS directly or via mutations such as RpoC(A494V). The balance between the activities of the housekeeping major sigma factor and σS sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase.IMPORTANCE An important general mechanism of a bacterium{\textquoteright}s adaptation to its environment involves adjusting the balance between growing fast and tolerating stresses. One paradigm where this plays out is in prolonged stationary phase: early studies showed that attenuation, but not complete elimination, of the general stress response enables early adaptation of the bacterium E. coli to the conditions established about 10 days into stationary phase. We show here that this balance is not static and that it is tilted back in favor of the general stress response about 2 weeks later. This can be established by direct mutations in the master regulator of the general stress response or by mutations in the core RNA polymerase enzyme itself. These conditions can support the development of antibiotic tolerance although the bacterium is not exposed to the antibiotic. Further exploration of the growth-stress balance over the course of stationary phase will necessarily require a deeper understanding of the events in the extracellular milieu.

}, doi = {10.1128/mSphere.00092-20}, author = {Nandy, P and Chib, S and Seshasayee, A} } @article {79734, title = {Mycobacterium tuberculosis ( Mtb) lipid mediated lysosomal rewiring in infected macrophages modulates intracellular Mtb trafficking and survival}, journal = {J Biol Chem}, volume = {295}, year = {2020}, month = {2020 Jul 03}, pages = {9192-9210}, abstract = {

Intracellular pathogens commonly manipulate the host lysosomal system for their survival. However, whether this pathogen-induced alteration affects the organization and functioning of the lysosomal system itself is not known. Here, using and infections and quantitative image analysis, we show that the lysosomal content and activity are globally elevated in ()-infected macrophages. We observed that this enhanced lysosomal state is sustained over time and defines an adaptive homeostasis in the infected macrophage. Lysosomal alterations are caused by mycobacterial surface components, notably the cell wall-associated lipid sulfolipid-1 (SL-1), which functions through the mTOR complex 1 (mTORC1)-transcription factor EB (TFEB) axis in the host cells. An mutant lacking SL-1, Δ shows attenuated lysosomal rewiring compared with the WT in both and infections. Exposing macrophages to purified SL-1 enhanced the trafficking of phagocytic cargo to lysosomes. Correspondingly, Δ exhibited a further reduction in lysosomal delivery compared with the WT. Reduced trafficking of this mutant strain to lysosomes correlated with enhanced intracellular bacterial survival. Our results reveal that global alteration of the host lysosomal system is a defining feature of -infected macrophages and suggest that this altered lysosomal state protects host cell integrity and contributes to the containment of the pathogen.

}, issn = {1083-351X}, doi = {10.1074/jbc.RA120.012809}, author = {Sachdeva, Kuldeep and Goel, Manisha and Sudhakar, Malvika and Mehta, Mansi and Raju, Rajmani and Raman, Karthik and Singh, Amit and Sundaramurthy, Varadharajan} } @article {74443, title = {The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.}, journal = {Annu Rev Biochem}, year = {2020}, month = {2020 Mar 13}, abstract = {

Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well. The first part of this review focuses on how myosins convert the chemical energy of ATP hydrolysis into mechanical movement, followed by a description of existing therapeutic approaches to target human β-cardiac myosin. The next section focuses on the possibility of targeting nonmuscle members of the human myosin family for several diseases. We end the review by describing the roles of myosin in parasites and the therapeutic potential of targeting them to block parasitic invasion of their hosts. Expected final online publication date for the , Volume 89 is June 22, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

}, issn = {1545-4509}, doi = {10.1146/annurev-biochem-011520-105234}, author = {Trivedi, Darshan V and Nag, Suman and Spudich, Annamma and Ruppel, Kathleen M and Spudich, James A} } @article {77384, title = {Myosin II Filament Dynamics in Actin Networks Revealed with Interferometric Scattering Microscopy.}, journal = {Biophys J}, volume = {118}, year = {2020}, month = {2020 Apr 21}, pages = {1946-1957}, abstract = {

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood because of difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect and image individual membrane-attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as functions of ATP concentration, providing experimental evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2020.02.025}, author = {Mosby, Lewis S and Hundt, Nikolas and Young, Gavin and Fineberg, Adam and Polin, Marco and Mayor, Satyajit and Kukura, Philipp and K{\"o}ster, Darius V} } @article {79865, title = {Navigating paved paradise: Evaluating landscape permeability to movement for large mammals in two conservation priority landscapes in India}, journal = {BIOLOGICAL CONSERVATION}, volume = {247}, year = {2020}, month = {7/2020}, abstract = {

Human land use and activity results in the loss of habitat and biodiversity, and alters how animals move through landscapes. Spatially explicit information on where animal movement is affected at large spatial scales is crucial for prioritizing conservation efforts. We evaluated landscape permeability to movement in two conservation priority landscapes in India, the Western Ghats (WG) and Central India (CI). Using an agent-based model we simulated movement and dispersal of five wide-ranging species in WG (elephant, gaur, leopard, sambar and sloth bear) and four in CI (gaur, leopard, sambar and sloth bear). For each species we compared movement in the presence and absence of land-use land-cover, infrastructure and human population to identify areas where movement is impeded and reduced due to high-resistance features; unrestricted due to relatively low-resistance features; and increased and channelled due to surrounding high-resistance areas. In both landscapes, median movement was reduced. Human land-use, human population and high linear infrastructure density contribute the highest to impeded movement for all species. Natural areas constitute only 20-55\% and 50-70\% of unrestricted, increased and channelled movement areas in WG and CI respectively. This suggests that a large percentage of the landscape crucial for maintaining movement is not completely permeable. Such areas are often neglected in conservation planning. Our spatially explicit results help identify and prioritize areas where restoration or mitigation should be planned to improve permeability to movement for large mammals. Our approach can be used for other landscapes where data on large mammal movement is lacking.

}, doi = {10.1016/j.biocon.2020.108613}, author = {Jayadevan, Anisha and Nayak, Rajat and Karanth, Krithi K. and Krishnaswamy, Jagdish and DeFries, Ruth and Karanth, K. Ullas and Vaidyanathan, Srinivas} } @article {85904, title = {The Neurohumanities: An Emerging Partnership for Exploring the Human Experience.}, journal = {Neuron}, volume = {108}, year = {2020}, month = {2020 Nov 25}, pages = {590-593}, abstract = {

Neuroscience has an extraordinary opportunity to investigate issues historically addressed by the arts, humanities, and social sciences. As a guide, we suggest three features of meaningful progress in the collaborative field, the neurohumanities, which we illustrate through a discussion of "neural schemas."

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2020.10.019}, author = {Carew, Thomas J and Ramaswami, Mani} } @article {73638, title = {Neuromodulatory Selection of Motor Neuron Recruitment Patterns in a Visuomotor Behavior Increases Speed.}, journal = {Curr Biol}, year = {2020}, month = {2020 Feb 20}, abstract = {

Animals generate locomotion at different speeds to suit their behavioral needs. Spinal circuits generate locomotion at these varying speeds by sequential activation of different spinal interneurons and motor neurons. Larval zebrafish can generate slow swims for prey capture and exploration by activation of secondary motor neurons and much faster and vigorous swims during escape and struggle via additional activation of primary motor neurons. Neuromodulators are known to alter the motor output of spinal circuits, but their precise role in speed regulation is not well\ understood. Here, in the context of optomotor response (OMR), an innate evoked locomotor behavior, we show that dopamine (DA) provides an additional layer to regulation of swim speed in larval zebrafish. Activation of D1-like receptors increases swim speed during OMR in free-swimming larvae. By analyzing tail bend kinematics in head-restrained larvae, we show that the increase in speed is actuated by larger tail bends. Whole-cell patch-clamp recordings from motor neurons reveal that, during OMR, typically only secondary motor neurons are active, whereas primary motor neurons are quiescent. Activation of D1-like receptors increases intrinsic excitability and excitatory synaptic drive in primary and secondary motor neurons. These actions result in greater recruitment of motor neurons during OMR. Our findings provide an example of neuromodulatory reconfiguration of spinal motor neuron speed modules where members are selectively recruited and motor drive is increased to effect changes in locomotor speed. VIDEO ABSTRACT.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2019.12.064}, author = {Jha, Urvashi and Thirumalai, Vatsala} } @article {83044, title = {A new cryptic Cnemaspis Strauch (Squamata: Gekkonidae) from an isolated granite hill on the Mysore Plateau, Karnataka, India}, journal = {ZOOTAXA}, volume = {4845}, year = {2020}, month = {09/2020}, pages = {509-528}, abstract = {

We describe a cryptic new species of the Cnemaspis mysoriensis complex from an isolated rocky hillock near Yadiyur, Mandya District of south Karnataka, India. Cnemaspis siellapulvis sp. nov. can be diagnosed from all other peninsular Indian congeners by its small body size (SVL \<32 mm), presence of spine-like tubercles on the flanks, heterogeneous dorsal pholidosis, two or three femoral pores on each thigh separated on either side by eight poitless scales from a continuous series of two precloacal pores in males, tail with enlarged, strongly keeled, conical tubercles forming whorls, median row of sub-caudals smooth and slightly enlarged, and a distinct colour pattern. The new species can be diagnosed from members of C mysoriensis Glade by the number of femoral and precloacal pores and number of poreless scales separating these series, the number of dorsal tubercles rows at mid-body, the number of ventral scales across the belly at mid-body and subtle colour pattern differences; besides 13.4-21.4 \% uncorrected ND2 sequence divergence. In this paper, we define the Cnemaspis mysoriensis Glade and provide a diagnosis and comparison against peninsular Indian congeners. We also provide major diagnostic characters for members of the C. mysoriensis Glade. The discovery of yet another endemic species of Cnemaspis from one of the many isolated granite rocky hills on Mysore Plateau highlights the possibilities of presence of many more cryptic undescribed species.

}, doi = {10.11646/zootaxa.4845.4.3}, author = {Khandekar, Akshay and Thackeray, Tejas and Agarwal, Ishan} } @article {84065, title = {A new large-bodied, rupicolous Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) allied to Cnemaspis heteropholis Bauer, 2002 from the Central Western Ghats of Karnataka, India.}, journal = {Zootaxa}, volume = {4801}, year = {2020}, month = {2020 Jun 17}, pages = {zootaxa.4801.1.2}, abstract = {

We describe a new large-bodied, rupicolous Cnemaspis from near Sakleshpur in the Central Western Ghats of Karnataka, India. Cnemaspis magnifica sp. nov. is allied to C. heteropholis and can be diagnosed from all other Indian Cnemaspis by the absence of spine-like scales on flank; heterogeneous dorsal pholidosis, presence of only femoral pores in males, homogenous dorsal pholidosis of tail with small, smooth, regularly arranged, flattened, subimbricate scales, without whorls of enlarged tubercles, median row of sub-caudals enlarged and smooth. The new species differs from its closest congener C. heteropholis in body size, the number of longitudinal ventral scales, number of lamellae under digit I and IV of manus and pes, and subtle colour pattern differences; besides 9.1 \% uncorrected ND2 sequence divergence. We provide the first description of topotypic male of C. heteropholis along with data on its distribution and natural history. The discovery of Cnemaspis magnifica sp. nov. with minimal field survey effort indicates the need for further herpetological exploration in the region.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4801.1.2}, author = {Khandekar, Akshay and Thackeray, Tejas and Pal, Saunak and Agarwal, Ishan} } @article {83744, title = {A new medium-bodied rupicolous Hemidactylus Goldfuss, 1820 (Squamata: Gekkonidae) from the Sirumalai massif, Tamil Nadu, India}, journal = {ZOOTAXA}, volume = {4852}, year = {2020}, month = {09/2020}, pages = {83-100}, abstract = {

We describe a new species of the Hemidactylus acanthopholis clade from Sirumalai, an isolated massif in the Dindigul district of Tamil Nadu state, India. Hemidactylus sirumalaiensis sp. nov. can be diagnosed from all members of the prashadi group by its medium body size (SVL \<95 mm), the number of dorsal tubercles rows at mid-body, the number of enlarged tubercles in paravertebral rows, the number of femoral pores and poreless scales between series of left and right femoral pores on the femoral-precloacal row in males, the number of ventral scales across the belly at mid-body and subtle colour pattern differences. The new species is the fourth member of the acanthopholis clade and 8.5-13.4 \% divergent in ND2 sequence data from other members of the clade. We also provide data on additional specimens from a new locality of Hemidactylus kolliensis, previously known only from the male holotype. Hemidactylus sirumalaiensis sp. nov. is the first endemic and only the other vertebrate species described from Sirumalai massif in the last 133 years. Most rupicolous Hemidactylus species from peninsular India outside the Western Ghats are known only from a few localities and are likely to be geographically restricted in distribution, and large areas of suitable habitat remain unsurveyed, suggesting many more allied species remain to be discovered.

}, doi = {10.11646/zootaxa.4852.1.4}, author = {Khandekar, Akshay and Thackeray, Tejas and Pawar, Swapnil and Agarwal, Ishan} } @article {87678, title = {New records of polymorphism in Asian libellulid dragonflies (Insecta: Odonata)}, journal = {INTERNATIONAL JOURNAL OF ODONATOLOGY}, volume = {23}, year = {2020}, month = {10/2020}, pages = {337-356}, abstract = {

Polymorphism has rarely been reported from dragonflies of the Libellulidae (Odonata: Anisoptera) family. Here, we report female-limited polymorphism in females of five species of the Libellulidae and a gynandromorph male ofBrachythemis contaminatafrom South Asia.We describe the morphological variation between andromorph and heteromorph females, and collate records of andromorph females from various sources. Yearly number of andromorph female ofCrocothemis servilia, Urotemis signataandNeurothemis signatawas calculated using records form published literature and unpublished sources, and social media.

}, doi = {10.1080/13887890.2020.1788999}, author = {Joshi, Shantanu and van der Poorten, Nancy and Sumanapala, Amila and Nielsen, Erland and Patel, Jenis and Nielsen, Bo and Sawant, Dattaprasad and Sherif, Muhamed} } @article {77383, title = {A new species of green pit vipers of the genus Trimeresurus Lacepede, 1804 (Reptilia, Serpentes, Viperidae) from western Arunachal Pradesh, India}, journal = {ZOOSYSTEMATICS AND EVOLUTION}, volume = {96}, year = {2020}, month = {04/2020}, pages = {123-138}, abstract = {

A new species of green pit vipers of the genus Trimeresurus Lacepede, 1804 is described from the lowlands of western Arunachal Pradesh state of India. The new species, Trimeresurus salazar, is a member of the subgenus Trimeresurus, a relationship deduced contingent on two mitochondrial genes, I 6S and ND4, and recovered as sister to Trimeresurus septentrionalis Kramer, 1977. The new species differs from the latter in bearing an orange to reddish stripe running from the lower border of the eye to the posterior part of the head in males, higher number of ptelygoid and dentary teeth, and a short, bilobed hemipenis. Description of the new species and T. arunachalensis Captain, Deepak, Pandit, Bhatt \& Athreya, 2019 from northeastern India in a span of less than one year highlights the need for dedicated surveys to document biodiversity across northeastern India.

}, doi = {10.3897/zse.96.48431}, author = {Mirza, ZA and Bhosale, HS and Phansalkar, PU and Sawant, M and Gowande, GG and Patel, H} } @article {83747, title = {A new species of Metallolophia Warren, 1895 (Lepidoptera: Geometridae: Geometrinae), and notes on M. opalina (Warren, 1893), from eastern Himalaya, India}, journal = {ZOOTAXA}, volume = {4838}, year = {2020}, month = {08/2020}, pages = {289-297}, abstract = {

A new species, Metallolophia tale ensis, sp. nov., is described and illustrated from Tale Wildlife Sanctuary, Lower Subansiri District. Arunachal Pradesh, India, based on male specimens. A second species, Metallolophia opalina (Warren, 1893), is recorded from India after more than a century, extending its range eastwards into Arunachal Pradesh, India.

}, doi = {10.11646/zootaxa.4838.2.9}, author = {Sondhi, Sanjay and Basu, Dipendra Nath and Sondhi, Yash and Kunte, Krushnamegh} } @article {88387, title = {A new species of snail-eating snakes of the genus Pareas Wagler, 1830 (Reptilia: Serpentes) from eastern Himalayas, India}, journal = {EUROPEAN JOURNAL OF TAXONOMY}, volume = {729}, year = {2020}, month = {12/2020}, pages = {54-73}, abstract = {

A new species of snail-eating snakes of the genus Pareas Wagler, 1830 is described from the eastern Himalayas. The species Pareas kaduri sp. nov. differs from all known species of the genus in bearing the following suite of characters: SVL 455-550 mm, TaL/TL 0.184-0.207, brown dorsum with black transverse bands throughout the body, 15 dorsal scale rows throughout the body and mid-dorsal vertebral scale rows enlarged, 8 rows keeled in males, loreal not touching orbit, ventrals 160-183, subcaudals 65-70 in males, 52 in one female specimen, hemipenis short, unilobed and 6-7 maxillary teeth. Molecular data for mitochondrial 16S rRNA and cytochrome b genes further attest the distinctness of the new species, which was recovered as a member of the Pareas hamptoni clade. Our work brings the total number of species recognized within the genus Pareas to 20.

}, doi = {10.5852/ejt.2020.729.1191}, author = {Bhosale, Harshal and Phansalkar, Pushkar and Sawant, Mandar and Gowande, Gaurang and Patel, Harshil and Mirza, Z.A} } @article {79866, title = {A new species of South Asian Cnemaspis (Squamata: Gekkonidae) from the Eastern Ghats, India}, journal = {ZOOTAXA}, volume = {4802}, year = {2020}, month = {06/2020}, pages = {449-462}, abstract = {

We describe a new species from within the South Asian Glade of the polyphyletic gekkonid genus Cnemaspis from the Velikonda Range, in the Eastern Ghats, Andhra Pradesh, India. The new species is the smallest known Indian gekkonid and can be diagnosed from all Indian congeners by its small body size (SVL \<29 mm), the absence of spine-like scales on flank, heterogeneous dorsal pholidosis, presence of precloacal pores and no femoral pores in males, tail with enlarged, strongly keeled, conical tubercles forming whorls, median row of sub-caudals smooth and slightly enlarged, and a distinct colour pattern. This is the 12th species of Cnemaspis to be described from outside the Western Ghats and is the first endemic from the Velikonda region of the Eastern Ghats. The new species is only known from its type locality, a lowland riparian habitat (\<200 in asl.) in dry evergreen forest at the base of a similar to 1200 m asl. peak. This discovery extends the range of the genus in peninsular India by similar to 130-150 kilometres to the northeast and suggests the genus is likely to be even more widely distributed than understood. The new species is clearly allied to C. mysoriensis, C. otai and C. yercaudensis with which it shares superficial colour pattern and similar body size, but is the first species from outside the Western Ghats in which males lack femoral pores.

}, doi = {10.11646/zootaxa.4802.3.3}, author = {Agarwal, Ishan and Bauer, Aaron M. and Khandekar, Akshay} } @article {77366, title = {Noise-induced schooling of fish}, journal = {NATURE PHYSICS}, volume = {16}, year = {2020}, month = {04/2020}, pages = {488}, abstract = {

Groups of fish tend to move in an organized fashion. Here the authors investigate the behaviour of schools of freshwater fish and find that schooling is induced by noise; the smaller the group size, the greater the noise and hence the greater the alignment.

We report on the dynamics of collective alignment in groups of the cichlid fish Etroplus suratensis. Focusing on small- to intermediate-sized groups (10 less than or similar to N less than or similar to 100), we demonstrate that schooling (highly polarized and coherent motion) is noise induced, arising from the intrinsic stochasticity associated with finite numbers of interacting fish. The fewer the fish, the greater the (multiplicative) noise and therefore the greater the likelihood of alignment. Such rare empirical evidence tightly constrains the possible underlying interactions that govern fish alignment, suggesting that E. suratensis either spontaneously change their direction or copy the direction of another fish, without any local averaging (the otherwise canonical mechanism of collective alignment). Our study therefore highlights the importance of stochasticity in behavioural inference. Furthermore, rather than simply obscuring otherwise deterministic dynamics, noise can be fundamental to the characterization of emergent collective behaviours.

}, doi = {10.1038/s41567-020-0787-y}, author = {Jhawar, Jitesh and Morris, RG and Amith-Kumar, UR and Raj, MD and Rogers, T and Rajendran, H and Guttal, V} } @article {83746, title = {A novel, diminutive Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae from a sacred grove in Odisha, eastern India}, journal = {ZOOTAXA}, volume = {4852}, year = {2020}, month = {09/2020}, pages = {485-499}, abstract = {

We describe a distinct new species of Hemiphyllodactylus from a sacred grove near Humma in Ganjam District of Odisha state, eastern India. Hemiphyllodactylus minimus sp. nov. is the smallest member of the genus and can be diagnosed from all peninsular Indian congeners by its small body size (SVL \<= 32.2 mm, n=11), having 15-18 dorsal scales and eight or nine ventral scales at mid-body contained within one longitudinal eye diameter, nine or ten precloacal pores separated by 4-6 poreless scales from a series of six or seven femoral pores on each thigh in males, lamellar formula of manus 2222 and of pes 2332 \& 2333, as well as subtle colour pattern differences. Additionally, the new species is 16.0-22.7 \% divergent from all other peninsular Indian Hemiphyllodactylus in uncorrected ND2 sequence data. The new species is the first member of the genus described from Odisha state and also the first Hemiphyllodactylus known from \< 100 m asl. The discovery of Hemiphyllodactylus minimus sp. nov. from a low elevation coastal locality in the Eastern Ghats open ups the possibilities that the genus could be more widespread than currently understood and potentially harbour many more distinct undcscribcd lineages. Therefore, dedicated fine-scale sampling efforts are needed to uncover the true diversity and distribution of Hemiphyllodactylus in the region.

}, doi = {10.11646/zootaxa.4852.4.6}, author = {Mohapatra, Pratyush P. and Khandekar, Akshay and Dutta, Sushil K. and Mahapatra, Cuckoo and Agarwal, Ishan} } @article {79733, title = {A novel polyubiquitin chain linkage formed by viral Ubiquitin is resistant to host deubiquitinating enzymes.}, journal = {Biochem J}, volume = {477}, year = {2020}, month = {2020 Jun 26}, pages = {2193-2219}, abstract = {

The Baculoviridae family of viruses encode a viral Ubiquitin (vUb) gene. Though the vUb is homologous to the host eukaryotic Ubiquitin (Ub), its preservation in the viral genome indicates unique functions that are not compensated by the host Ub. We report the structural, biophysical, and biochemical properties of the vUb from Autographa californica multiple nucleo-polyhedrosis virus (AcMNPV). The packing of central helix α1 to the beta-sheet β1-β5 is different between vUb and Ub. Consequently, its stability is lower compared with Ub. However, the surface properties, ubiquitination activity, and the interaction with Ubiquitin-binding domains are similar between vUb and Ub. Interestingly, vUb forms atypical polyubiquitin chain linked by lysine at the 54th position (K54), and the deubiquitinating enzymes are ineffective against the K54-linked polyubiquitin chains. We propose that the modification of host/viral proteins with the K54-linked chains is an effective way selected by the virus to protect the vUb signal from host DeUbiquitinases.

}, issn = {1470-8728}, doi = {10.1042/BCJ20200289}, author = {Negi, Hitendra and Reddy, Pothula Purushotham and Vengayil, Vineeth and Patole, Chhaya and Laxman, Sunil and Das, Ranabir} } @article {77390, title = {N-terminal variant Asp14Asn of the human p70 S6 Kinase 1 enhances translational signaling causing different effects in developing and mature neuronal cells.}, journal = {Neurobiol Learn Mem}, volume = {171}, year = {2020}, month = {2020 May}, pages = {107203}, abstract = {

The ribosomal p70 S6 Kinase 1 (S6K1) has been implicated in the etiology of complex neurological diseases including autism, depression and dementia. Though no major gene disruption has been reported in humans in RPS6KB1, single nucleotide variants (SNVs) causing missense mutations have been identified, which have not been assessed for their impact on protein function. These S6K1 mutations have the potential to influence disease progression and treatment response. We mined the Simon Simplex Collection (SSC) and SPARK autism database to find inherited SNVs in S6K1 and characterized the effect of two missense SNVs, Asp14Asn (allele frequency\ =\ 0.03282\%) and Glu44Gln (allele frequency\ =\ 0.0008244\%), on S6K1 function in HEK293, human ES cells and primary neurons. Expressing Asp14Asn in HEK293 cells resulted in increased basal phosphorylation of downstream targets of S6K1 and increased de novo translation. This variant also showed blunted response to the specific S6K1 inhibitor, FS-115. In human embryonic cell line Shef4, Asp14Asn enhanced spontaneous neural fate specification in the absence of differentiating growth factors. In addition to enhanced translation, neurons expressing Asp14Asn exhibited impaired dendritic arborization and increased levels of phosphorylated ERK 1/2. Finally, in the SSC families tracked, Asp14Asn segregated with lower IQ scores when found in the autistic individual rather than the unaffected sibling. The Glu44Gln mutation showed a milder, but opposite phenotype in HEK cells as compared to Asp14Asn. Although the Glu44Gln mutation displayed increased neuronal translation, it had no impact on neuronal morphology. Our results provide the first characterization of naturally occurring human S6K1 variants on cognitive phenotype, neuronal morphology and maturation, underscoring again the importance of translation control in neural development and plasticity.

}, issn = {1095-9564}, doi = {10.1016/j.nlm.2020.107203}, author = {Venkatasubramani, Janani Priya and Subramanyam, Prakash and Pal, Rakhi and Reddy, Bharath K and Srinivasan, Durga Jeyalakshmi and Chattarji, Sumantra and Iossifov, Ivan and Klann, Eric and Bhattacharya, Aditi} } @article {85905, title = {Nutrients cause grassland biomass to outpace herbivory.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 11 27}, pages = {6036}, abstract = {

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ({\textquoteright}consumer-controlled{\textquoteright}). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ({\textquoteright}resource-controlled{\textquoteright}). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.

}, issn = {2041-1723}, doi = {10.1038/s41467-020-19870-y}, author = {Borer, E T and Harpole, W S and Adler, P B and Arnillas, C A and Bugalho, M N and Cadotte, M W and Caldeira, M C and Campana, S and Dickman, C R and Dickson, T L and Donohue, I and Eskelinen, A and Firn, J L and Graff, P and Gruner, D S and Heckman, R W and Koltz, A M and Komatsu, K J and Lannes, L S and MacDougall, A S and Martina, J P and Moore, J L and Mortensen, B and Ochoa-Hueso, R and Olde Venterink, H and Power, S A and Price, J N and Risch, A C and Sankaran, M and Sch{\"u}tz, M and Sitters, J and Stevens, C J and Virtanen, R and Wilfahrt, P A and Seabloom, E W} } @article {77386, title = {Ontogenic colour change, survival, and mating in the damselfly Agriocnemis pygmaea Rambur (Insecta: Odonata)}, journal = {ECOLOGICAL ENTOMOLOGY}, year = {2020}, month = {04/2020}, abstract = {

1. Damselflies often show intra-specific colour variation, which may represent genetic polymorphism or age-related (ontogenic) colour changes.

2. Such variation has distinct implications for the species{\textquoteright} ecology and evolution. Colour variation in females of the damselfly Agriocnemis pygmaea was studied, which range from blue male-like individuals (andromorphs) to those with a distinct red colour (heteromorphs). From preliminary observations, it was hypothesised that this species exhibits ontogenic colour change from heteromorph to andromorph coloration.

3. Mark-recapture experiments and egg counts of dissected females suggested that immature females are heteromorphic and gradually begin to resemble males as they attain sexual maturity.

4. Reflectance spectra of field-caught individuals indicated that, although males are indistinguishable from andromorphs, they could be easily differentiated from heteromorphs.

5. Finally, field observations and mate choice experiments showed that males rarely attempt to mate with heteromorphic females and prefer andromorphs. Together, this study{\textquoteright}s results suggest that the observed colour variation in A. pygmaea females is ontogenic and is associated with sexual maturity.

}, doi = {10.1111/een.12879}, author = {Joshi, S and Agashe, D} } @article {83636, title = {Opinion: Envisioning a biodiversity science for sustaining human well-being.}, journal = {Proc Natl Acad Sci U S A}, year = {2020}, month = {2020 Sep 30}, issn = {1091-6490}, doi = {10.1073/pnas.2018436117}, author = {Bawa, Kamaljit S and Nawn, Nandan and Chellam, Ravi and Krishnaswamy, Jagdish and Mathur, Vinod and Olsson, Shannon B and Pandit, Nitin and Rajagopal, Prabhakar and Sankaran, Mahesh and Shaanker, R Uma and Shankar, Darshan and Ramakrishnan, Uma and Vanak, Abi Tamim and Quader, Suhel} } @article {77997, title = {Opportunities for prioritizing and expanding conservation enterprise in India using a guild of carnivores as flagships}, journal = {ENVIRONMENTAL RESEARCH LETTERS}, volume = {15}, year = {2020}, month = {06/2020}, abstract = {

Conservation interventions in developing countries are frequently thwarted by socio-economic agendas, severely limiting the scope and rigor of biodiversity and habitat conservation. Very few ecological assessments incorporate human interests in conservation prioritization, creating asynchrony between planning and implementation. For conservation actions to be logistically feasible, multiple criteria including ecological, social, economic and administrative aspects must be considered. Understanding how these different dimensions interact spatially is also important for gauging the potential for conservation success. Here, we use a guild of select mammalian carnivores (wild canids and hyenas) in India to (i) generate distribution maps at the spatial scale of administrative sub-districts, that are relevant to management, (ii) examine ecological, social and biogeographic factors associated with their distribution, assess key threats, and identify areas important for their conservation, (iii) use prioritization tools for balancing habitat conservation, human needs and economic growth, and (iv) evaluate the spatial congruence between areas with high conservation potential, and areas currently in focus for protection efforts, conservation investments, and infrastructure development. We find that the current Protected Area system does not adequately cover or represent diverse habitats, that there is immense potential for States to increase financial investments towards alternative conservation strategies, and, most infrastructure projects may be potentially jeopardizing important carnivore habitats where the two overlap. Our framework allowed for identifying locations where conservation investments would lead to the highest benefits for carnivores as flagships, which also benefit other species across habitats. We make a case for re-evaluating how large-scale prioritization assessments are made, and for broadening the purview of conservation policies in India and other developing countries.

}, doi = {10.1088/1748-9326/ab7e50}, author = {Srivathsa, A and Majgaonkar, I and Sharma, S and Singh, P and Punjabi, GA and Chawla, MM and Banerjee, A} } @article {78179, title = {Pan-cancer Analysis of Whole Genomes}, journal = {Nature}, volume = {578}, year = {2020}, month = {02/2020}, pages = {82-93}, abstract = {

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5\% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes

}, doi = {10.1038/s41586-020-1969-6 }, author = {ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium and Sabarinathan, R and et al} } @article {73639, title = {Phenotypic diversity of Methylobacterium associated with rice landraces in North-East India.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0228550}, abstract = {

The ecology and distribution of many bacteria is strongly associated with specific eukaryotic hosts. However, the impact of such host association on bacterial ecology and evolution is not well understood. Bacteria from the genus Methylobacterium consume plant-derived methanol, and are some of the most abundant and widespread plant-associated bacteria. In addition, many of these species impact plant fitness. To determine the ecology and distribution of Methylobacterium in nature, we sampled bacteria from 36 distinct rice landraces, traditionally grown in geographically isolated locations in North-East (NE) India. These landraces have been selected for diverse phenotypic traits by local communities, and we expected that the divergent selection on hosts may have also generated divergence in associated Methylobacterium strains. We determined the ability of 91 distinct rice-associated Methylobacterium isolates to use a panel of carbon sources, finding substantial variability in carbon use profiles. Consistent with our expectation, across spatial scales this phenotypic variation was largely explained by host landrace identity rather than geographical factors or bacterial taxonomy. However, variation in carbon utilisation was not correlated with sugar exudates on leaf surfaces, suggesting that bacterial carbon use profiles do not directly determine bacterial colonization across landraces. Finally, experiments showed that at least some rice landraces gain an early growth advantage from their specific phyllosphere-colonizing Methylobacterium strains. Together, our results suggest that landrace-specific host-microbial relationships may contribute to spatial structure in rice-associated Methylobacterium in a natural ecosystem. In turn, association with specific bacteria may provide new ways to preserve and understand diversity in one of the most important food crops of the world.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0228550}, author = {Sanjenbam, Pratibha and Buddidathi, Radhika and Venkatesan, Radhika and Shivaprasad, P V and Agashe, Deepa} } @article {87597, title = {A phylogenetic and taxonomic review of baviine jumping spiders (Araneae, Salticidae, Baviini).}, journal = {Zookeys}, volume = {1004}, year = {2020}, month = {2020}, pages = {27-97}, abstract = {

The systematics and taxonomy of the tropical Asian jumping spiders of the tribe Baviini is reviewed, with a molecular phylogenetic study (UCE sequence capture, traditional Sanger sequencing) guiding a reclassification of the group{\textquoteright}s genera. The well-studied members of the group are placed into six genera: Simon, 1877, Caleb \& Sankaran, 2019, Simon, 1901, Thorell, 1895, Simon, 1885, and one new genus, Maddison, The identity of is clarified, and Kanesharatnam \& Benjamin, 2018 synonymized with it. Strand, 1911 is synonymized with . The molecular phylogeny divides the baviines into three clades, the clade with a long embolus (, ), the genus with a flat body and short embolus, and the clade with a higher body and (usually) short embolus (remaining genera). In general, morphological synapomorphies support or extend the molecularly delimited groups. Eighteen new species are described: , , , , , , , , (type species of ), , , , , , , , , and , all , with taxonomic authority W. Maddison. The distinctions between baviines and the astioid {\.Z}abka, 1985 are reviewed, leading to four species being moved into from and other genera. Fifteen new combinations are established: (Freudenschuss \& Seiter, 2016), (Simon, 1903), (Pr{\'o}szy{\'n}ski \& Deeleman-Reinhold, 2013), (Berry, Beatty \& Pr{\'o}szy{\'n}ski, 1997), (Pr{\'o}szy{\'n}ski \& Deeleman-Reinhold, 2013), (Cao \& Li, 2016), (Reimoser, 1929), (Thorell, 1881), (Keyserling, 1883), (Strand, 1911), (Cao \& Li, 2016), (Simon, 1900), (Cao \& Li, 2016), (Kanesharatnam \& Benjamin, 2018), (Strand, 1911), all One combination is restored, (C. L. Koch, 1846). Five of these new or restored combinations correct previous errors of placing species in genera that have superficially similar palps but extremely different body forms, in fact belonging in distantly related tribes, emphasizing that the general shape of male palps should be used with caution in determining relationships. A little-studied genus, Pr{\'o}szy{\'n}ski, 2018, is tentatively assigned to the Baviini. Thorell, 1895 is assigned to the Ballini.

}, issn = {1313-2989}, doi = {10.3897/zookeys.1004.57526}, author = {Maddison, Wayne P and Beattie, Imara and Marathe, Kiran and Ng, Paul Y C and Kanesharatnam, Nilani and Benjamin, Suresh P and Kunte, Krushnamegh} } @article {78021, title = {A PI4KIIIα protein complex is required for cell viability during Drosophila wing development.}, journal = {Dev Biol}, volume = {462}, year = {2020}, month = {2020 Jun 15}, pages = {208-222}, abstract = {

Phosphatidylinositol 4 phosphate (PI4P) and phosphatidylinositol 4,5 bisphosphate [PI(4,5)P] are enriched on the inner leaflet of the plasma membrane and proposed to be key determinants of its function. PI4P is also the biochemical precursor for the synthesis of PI(4,5)P but can itself also bind to and regulate protein function. However, the independent function of PI4P at the plasma membrane in supporting cell function in metazoans during development in vivo remains unclear. We find that conserved components of a multi-protein complex composed of phosphatidylinositol 4-kinase IIIα (PI4KIIIα), TTC7 and Efr3 is required for normal vein patterning and wing development. Depletion of each of these three components of the PI4KIIIα complex in developing wing cells results in altered wing morphology. These effects are associated with an increase in apoptosis and can be rescued by expression of an inhibitor of Drosophila caspase. We find that in contrast to previous reports, PI4KIIIα depletion does not alter key outputs of hedgehog signalling in developing wing discs. Depletion of PI4KIIIα results in reduced PI4P levels at the plasma membrane of developing wing disc cells while levels of PI(4,5)P, the downstream metabolite of PI4P, are not altered. Thus, PI4P itself generated by the activity of the PI4KIIIα complex plays an essential role in supporting cell viability in the developing Drosophila wing disc.

}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2020.03.008}, author = {Basu, Urbashi and Balakrishnan, Sruthi S and Janardan, Vishnu and Raghu, Padinjat} } @article {83750, title = {Plant-virus-insect tritrophic interactions: insights into the functions of geminivirus virion-sense strand genes.}, journal = {Proc Biol Sci}, volume = {287}, year = {2020}, month = {2020 Oct 14}, pages = {20201846}, abstract = {

The genome of the plant-infecting viruses in the family Geminiviridae is composed of one or two circular single stranded DNA of approximately 2.7-5.2 kb in length. These viruses have emerged as the most devastating pathogen infecting a large number of crops and weeds across the continents. They code for fewer open reading frames (ORFs) through the generation of overlapping transcripts derived from the bidirectional viral promoters. Members of geminiviruses code for up to four ORFs in the virion-sense strand, and their gene expression is regulated by various -elements located at their promoters in the intergenic region. These viral proteins perform multiple functions at every stage of the viral life cycle such as virus transport, insect-mediated virus transmission and suppression of host defence. They impede the host{\textquoteright}s multi-layered antiviral mechanisms including gene silencing (at transcriptional and post-transcriptional levels) and hypersensitive response. This review summarizes the essential role of virion-sense strand encoded proteins in transport of viral genomes within and between plant cells, countering defence in hosts (both plants and the insects), and also in the ubiquitous role in vector-mediated transmission. We highlight the significance of their pro-viral activities in manipulating host-derived innate immune responses and the interaction with whitefly-derived proteins. We also discuss the current knowledge on virus replication and transcription within the insect body.

}, issn = {1471-2954}, doi = {10.1098/rspb.2020.1846}, author = {Vinoth Kumar, R and Shivaprasad, P V} } @article {78165, title = {Plasmodium vivax liver stage assay platforms using Indian clinical isolates.}, journal = {Malar J}, volume = {19}, year = {2020}, month = {2020 Jun 22}, pages = {214}, abstract = {

BACKGROUND: Vivax malaria is associated with significant morbidity and economic loss, and constitutes the bulk of malaria cases in large parts of Asia and South America as well as recent case reports in Africa. The widespread prevalence of vivax is a challenge to global malaria elimination programmes. Vivax malaria control is particularly challenged by existence of dormant liver stage forms that are difficult to treat and are responsible for multiple relapses, growing drug resistance to the asexual blood stages and host-genetic factors that preclude use of specific drugs like primaquine capable of targeting Plasmodium vivax liver stages. Despite an obligatory liver-stage in the Plasmodium life cycle, both the difficulty in obtaining P. vivax sporozoites and the limited availability of robust host cell models permissive to P. vivax infection are responsible for the limited knowledge of hypnozoite formation biology and relapse mechanisms, as well as the limited capability to do drug screening. Although India accounts for about half of vivax malaria cases world-wide, very little is known about the vivax liver stage forms in the context of Indian clinical isolates.

METHODS: To address this, methods were established to obtain infective P. vivax sporozoites from an endemic region in India and multiple assay platforms set up to detect and characterize vivax liver stage forms. Different hepatoma cell lines, including the widely used HCO4 cells, primary human hepatocytes as well as hepatocytes obtained from iPSC{\textquoteright}s generated from vivax patients and healthy donors were tested for infectivity with P. vivax sporozoites.

RESULTS: Both large and small forms of vivax liver stage are detected in these assays, although the infectivity obtained in these platforms are low.

CONCLUSIONS: This study provides a proof of concept for detecting liver stage P. vivax and provide the first characterization of P. vivax liver stage forms from an endemic region in India.

}, issn = {1475-2875}, doi = {10.1186/s12936-020-03284-8}, author = {Subramani, Pradeep A and Vartak-Sharma, Neha and Sreekumar, Seetha and Mathur, Pallavi and Nayer, Bhavana and Dakhore, Sushrut and Basavanna, Sowmya K and Kalappa, Devaiah M and Krishnamurthy, Ramya V and Mukhi, Benudhar and Mishra, Priyasha and Yoshida, Noriko and Ghosh, Susanta Kumar and Shandil, Radhakrishan and Narayanan, Shridhar and Campo, Brice and Hasegawa, Kouichi and Anvikar, Anupkumar R and Valecha, Neena and Sundaramurthy, Varadharajan} } @article {84572, title = {Pooling Samples to Increase SARS-CoV-2 Testing.}, journal = {J Indian Inst Sci}, year = {2020}, month = {2020 Oct 18}, pages = {1-6}, abstract = {

As SARS-CoV-2 continues to propagate around the world, it is becoming increasingly important to scale up testing. This is necessary both at the individual level, to inform diagnosis, treatment and contract tracing, as well as at the population level to inform policies to control spread of the infection. The gold-standard RT-qPCR test for the virus is relatively expensive and takes time, so combining multiple samples into "pools" that are tested together has emerged as a useful way to test many individuals with less than one test per person. Here, we describe the basic idea behind pooling of samples and different methods for reconstructing the result for each individual from the test of pooled samples. The methods range from simple pooling, where each pool is disjoint from the other, to more complex combinatorial pooling where each sample is split into multiple pools and each pool has a specified combination of samples. We describe efforts to validate these testing methods clinically and the potential advantages of the combinatorial pooling method named Tapestry Pooling that relies on compressed sensing techniques.

}, issn = {0970-4140}, doi = {10.1007/s41745-020-00204-2}, author = {Gopalkrishnan, Manoj and Krishna, Sandeep} } @article {84070, title = {Predicting biodiversity richness in rapidly changing landscapes: climate, low human pressure or protection as salvation?}, year = {2020}, month = {2020/10/09}, abstract = {

Rates of biodiversity loss in Southeast Asia are among the highest in the world, and the Indo-Burma and South-Central China Biodiversity Hotspots rank among the world{\textquoteright}s most threatened. Developing robust multi-species conservation models is critical for stemming biodiversity loss both here and globally. We used a large and geographically extensive remote-camera survey and multi-scale, multivariate optimization species distribution modelling to investigate the factors driving biodiversity across these two adjoining biodiversity hotspots. Four major findings emerged from the work. (i) We identified clear spatial patterns of species richness, with two main biodiverse centres in the Thai-Malay Peninsula and in the mountainous region of Southwest China. (ii) Carnivores in particular, and large ungulates to a lesser degree, were the strongest indicators of species richness. (iii) Climate had the largest effect on biodiversity, followed by protected status and human footprint. (iv) Gap analysis between the biodiversity model and the current system of protected areas revealed that the majority of areas supporting the highest predicted biodiversity are not protected. Our results highlighted several key locations that should be prioritized for expanding the protected area network to maximize conservation effectiveness. We demonstrated the importance of switching from single-species to multi-species approaches to highlight areas of high priority for biodiversity conservation. In addition, since these areas mostly occur over multiple countries, we also advocate for a paradigmatic focus on transboundary conservation planning.

}, isbn = {1572-9710}, url = {https://doi.org/10.1007/s10531-020-02062-x}, author = {Macdonald, David W. and Chiaverini, Luca and Bothwell, Helen M. and Kaszta, {\.Z}aneta and Ash, Eric and Bolongon, Gilmoore and Can, {\"O}zg{\"u}n Emre and Campos-Arceiz, Ahimsa and Channa, Phan and Clements, Gopalasamy Reuben and Hearn, Andrew J. and Hedges, Laurie and Htun, Saw and Kamler, Jan F. and Macdonald, Ewan A. and Moore, Jonathan and Naing, Hla and Onuma, Manabu and Rasphone, Akchousanh and Rayan, D. Mark and Ross, Joanna and Singh, Priya and Tan, Cedric Kai Wei and Wadey, Jamie and Yadav, Bhupendra P. and Cushman, Samuel A.} } @article {77385, title = {The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts.}, journal = {BMC Mol Cell Biol}, volume = {21}, year = {2020}, month = {2020 Apr 15}, pages = {25}, abstract = {

BACKGROUND: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood.

RESULTS: Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1.

CONCLUSIONS: Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.

}, issn = {2661-8850}, doi = {10.1186/s12860-020-00266-1}, author = {Venugopal, Nisha and Ghosh, Ananga and Gala, Hardik and Aloysius, Ajoy and Vyas, Neha and Dhawan, Jyotsna} } @article {78112, title = {Promiscuity and specificity of eukaryotic glycosyltransferases.}, journal = {Biochem Soc Trans}, year = {2020}, month = {2020 Jun 15}, abstract = {

Glycosyltransferases are a large family of enzymes responsible for covalently linking sugar monosaccharides to a variety of organic substrates. These enzymes drive the synthesis of complex oligosaccharides known as glycans, which play key roles in inter-cellular interactions across all the kingdoms of life; they also catalyze sugar attachment during the synthesis of small-molecule metabolites such as plant flavonoids. A given glycosyltransferase enzyme is typically responsible for attaching a specific donor monosaccharide, via a specific glycosidic linkage, to a specific moiety on the acceptor substrate. However these enzymes are often promiscuous, able catalyze linkages between a variety of donors and acceptors. In this review we discuss distinct classes of glycosyltransferase promiscuity, each illustrated by enzymatic examples from small-molecule or glycan synthesis. We highlight the physical causes of promiscuity, and its biochemical consequences. Structural studies of glycosyltransferases involved in glycan synthesis show that they make specific contacts with {\textquoteright}recognition motifs{\textquoteright} that are much smaller than the full oligosaccharide substrate. There is a wide range in the sizes of glycosyltransferase recognition motifs: highly promiscuous enzymes recognize monosaccharide or disaccharide motifs across multiple oligosaccharides, while highly specific enzymes recognize large, complex motifs found on few oligosaccharides. In eukaryotes, the localization of glycosyltransferases within compartments of the Golgi apparatus may play a role in mitigating the glycan variability caused by enzyme promiscuity.

}, issn = {1470-8752}, doi = {10.1042/BST20190651}, author = {Biswas, Ansuman and Thattai, Mukund} } @article {79868, title = {Protected areas and benthic characteristics influence the distribution of the Vulnerable bumphead parrotfishBolbometopon muricatumin the Andaman and Nicobar Islands, India}, journal = {ORYX}, volume = {54}, year = {2020}, month = {07/2020}, pages = {564-571}, abstract = {

The Vulnerable bumphead parrotfishBolbometopon muricatum, a highly prized fishery resource worldwide, has experienced population declines throughout its geographical range. There is limited knowledge of the distribution and abundance of, and threats to, this fish in Indian waters, particularly for the Andaman and Nicobar Islands. To assess the species{\textquoteright} distribution and conservation status we conducted underwater surveys across 75 sites around 51 islands and interviewed 99 fishers across the Andaman and Nicobar archipelago. We recorded a total of 59 individualB. muricatumacross nine sites from the northernmost island in the Andamans (Landfall Island) to the southernmost island in the Nicobars (Great Nicobar Island). Interviews revealed that most fishers (100\% in Nicobar, 94\% in Middle Andaman, 62\% in South Andaman) had seenB. muricatum, and knowledge of the species is highest amongst spearfishers. Generalized linear models indicated that presence of marine protected areas and high live coral cover influenced the abundance and distribution ofB. muricatum. The species{\textquoteright} density seems to be naturally low in the archipelago. We discuss our findings in the light of protecting rare and threatened species, and recommend strengthening the existing marine protected areas in these islands.

}, doi = {10.1017/S0030605318000376}, author = {Patankar, Vardhan and Wagh, Tanmay and Marathe, Aniruddha} } @article {80848, title = {Protein energy landscape exploration with structure-based models.}, journal = {Curr Opin Struct Biol}, volume = {64}, year = {2020}, month = {2020 Aug 11}, pages = {145-151}, abstract = {

Exploring the multi-dimensional energy landscape of a large protein in detail is a computational challenge. Such investigations may include analysis of multiple folding pathways, rate constants for important conformational transitions, locating intermediate states populated during folding, estimating energetic and entropic barriers that separate populated basins, and visualising a high-dimensional surface. The complexity of the landscape can be simplified through coarse-grained structure-based models (SBMs). These widely used coarse-grained representations of proteins provide a minimalist approximation to the free energy landscape, which subsumes the folding behaviour of many single-domain proteins. Here we describe the combination of SBMs with discrete path sampling (DPS), and show how this approach can provide details of the landscape and folding pathways. Combining SBMs and DPS provides an efficient framework for sampling the protein free energy landscape and for calculating various kinetic and thermodynamic quantities.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2020.07.003}, author = {Neelamraju, Sridhar and Wales, David J and Gosavi, Shachi} } @article {81591, title = {Quaternary variations in the structural assembly of N-acetylglucosamine-6-phosphate deacetylase from Pasteurella multocida.}, journal = {Proteins}, year = {2020}, month = {2020 Aug 31}, abstract = {

N-acetylglucosamine 6-phosphate deacetylase (NagA) catalyzes the conversion of N-acetylglucosamine-6-phosphate to glucosamine-6-phosphate in amino sugar catabolism. This conversion is an essential step in the catabolism of sialic acid in several pathogenic bacteria, including Pasteurella multocida, and thus NagA is identified as a potential drug target. Here, we report the unique structural features of NagA from P. multocida (PmNagA) resolved to 1.95 {\r a}. PmNagA displays an altered quaternary architecture with unique interface interactions compared to its close homolog, the Escherichia coli NagA (EcNagA). We confirmed that the altered quaternary structure is not a crystallographic artefact using single particle electron cryo-microscopy. Analysis of the determined crystal structure reveals a set of hot-spot residues involved in novel interactions at the dimer-dimer interface. PmNagA binds to one Zn ion in the active site and demonstrates kinetic parameters comparable to other bacterial homologs. Kinetic studies reveal that at high substrate concentrations (~10-fold the K ), the tetrameric PmNagA displays hysteresis similar to its distant neighbor, the dimeric Staphylococcus aureus NagA (SaNagA). Our findings provide key information on structural and functional properties of NagA in P. multocida that could be utilized to design novel antibacterials. This article is protected by copyright. All rights reserved.

}, issn = {1097-0134}, doi = {10.1002/prot.25996}, author = {Manjunath, Lavanyaa and Coombes, David and Davies, James and Dhurandhar, Mugdha and Tiwari, Vikas R and Dobson, Renwick C J and Sowdhamini, R and Ramaswamy, S and Bose, Sucharita} } @article {79800, title = {A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 Jul 17}, pages = {3598}, abstract = {

Genetic variation at the 8q24 locus is linked with the greater susceptibility to prostate cancer in men of African ancestry. One such African ancestry specific rare variant, rs72725854 (A\>G/T) (~6\% allele frequency) has been associated with a ~2-fold increase in prostate cancer risk. However, the functional relevance of this variant is unknown. Here we show that the variant rs72725854 is present in a prostate cancer-specific enhancer at 8q24 locus. Chromatin-conformation capture and dCas9 mediated enhancer blocking establish a direct regulatory link between this enhancer and lncRNAs PCAT1, PRNCR1 and PVT1. The risk allele ({\textquoteright}T{\textquoteright}) is associated with higher expression of PCAT1, PVT1 and c-myc in prostate tumors. Further, enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. Elevated expression of these lncRNAs and c-myc in risk allele carriers may explain their greater susceptibility to prostate cancer.

}, issn = {2041-1723}, doi = {10.1038/s41467-020-17325-y}, author = {Walavalkar, Kaivalya and Saravanan, Bharath and Singh, Anurag Kumar and Jayani, Ranveer Singh and Nair, Ashwin and Farooq, Umer and Islam, Zubairul and Soota, Deepanshu and Mann, Rajat and Shivaprasad, Padubidri V and Freedman, Matthew L and Sabarinathan, Radhakrishnan and Haiman, Christopher A and Notani, Dimple} } @article {83642, title = {The red flour beetle Tribolium castaneum: A model for host-microbiome interactions.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0239051}, abstract = {

A large body of ongoing research focuses on understanding the mechanisms and processes underlying host-microbiome interactions, and predicting their ecological and evolutionary outcomes. To draw general conclusions about such interactions and understand how they are established, we must synthesize information from a diverse set of species. We analysed the microbiome of an important insect model-the red flour beetle Tribolium castaneum-which is a widespread generalist pest of stored cereals. The beetles complete their entire life cycle in flour, which thus serves multiple functions: habitat, food, and a source of microbes. We determined key factors that shape the T. castaneum microbiome, established protocols to manipulate it, and tested its consequences for host fitness. We show that the T. castaneum microbiome is derived from flour-acquired microbes, and varies as a function of (flour) resource and beetle density. Beetles gain multiple fitness benefits from their microbiome, such as higher fecundity, egg survival, and lifespan; and reduced cannibalism. In contrast, the microbiome has a limited effect on development rate, and does not enhance pathogen resistance. Importantly, the benefits are derived only from microbes in the ancestral resource (wheat flour), and not from novel resources such as finger millet, sorghum, and corn. Notably, the microbiome is not essential for beetle survival and development under any of the tested conditions. Thus, the red flour beetle is a tractable model system to understand the ecology, evolution and mechanisms of host-microbiome interactions, while closely mimicking the host species{\textquoteright} natural niche.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0239051}, author = {Agarwal, Aparna and Agashe, Deepa} } @article {83650, title = {Regulation of neuronal physiology by Ca2+ release through the IP3R}, journal = {Current Opinion in Physiology}, volume = {17}, year = {2020}, month = {10/10}, pages = {1-8}, abstract = {

Identification of mutations in the gene encoding the inositol 1,4,5-trisphosphate receptor Type 1 (IP3R1) as causative for Spinocerebellar Ataxia 15, 29 and Gillespie Syndrome emphasize the importance of understanding how the IP3R impacts neuronal function and physiology. Here we discuss how cellular changes due to IP3 mediated Ca2+release affect systemic physiology in Drosophila and mouse. The relevance of these findings to recently identified human neurological conditions are also discussed.

}, doi = {10.1016/j.cophys.2020.06.001}, author = {Hasan, Gaiti and Sharma, Anamika} } @article {83634, title = {Relative influence of wild prey and livestock abundance on carnivore-caused livestock predation}, journal = {ECOLOGY AND EVOLUTION}, year = {2020}, month = {2020}, abstract = {

Conservation conflict over livestock depredation is one of the key drivers of large mammalian carnivore declines worldwide. Mitigating this conflict requires strategies informed by reliable knowledge of factors influencing livestock depredation. Wild prey and livestock abundance are critical factors influencing the extent of livestock depredation. We compared whether the extent of livestock predation by snow leopardsPanthera unciadiffered in relation to densities of wild prey, livestock, and snow leopards at two sites in Shey Phoksundo National Park, Nepal. We used camera trap-based spatially explicit capture-recapture models to estimate snow leopard density; double-observer surveys to estimate the density of their main prey species, the blue sheepPseudois nayaur; and interview-based household surveys to estimate livestock population and number of livestock killed by snow leopards. The proportion of livestock lost per household was seven times higher in Upper Dolpa, the site which had higher snow leopard density (2.51 snow leopards per 100 km(2)) and higher livestock density (17.21 livestock per km(2)) compared to Lower Dolpa (1.21 snow leopards per 100 km(2); 4.5 livestock per km(2)). The wild prey density was similar across the two sites (1.81 and 1.57 animals per km(2)in Upper and Lower Dolpa, respectively). Our results suggest that livestock depredation level may largely be determined by the abundances of the snow leopards and livestock and predation levels on livestock can vary even at similar levels of wild prey density. In large parts of the snow leopard range, livestock production is indispensable to local livelihoods and livestock population is expected to increase to meet the demand of cashmere. Hence, we recommend that any efforts to increase livestock populations or conservation initiatives aimed at recovering or increasing snow leopard population be accompanied by better herding practices (e.g., predator-proof corrals) to protect livestock from snow leopard.

}, doi = {10.1002/ece3.6815}, author = {Khanal, Gopal and Mishra, Charudutt and Suryawanshi, Kulbhushansingh R} } @article {73074, title = {The repertoire of mutational signatures in human cancer}, journal = {Nature}, volume = {578}, year = {2020}, month = {02/2020}, pages = {94-101}, abstract = {

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690\ somatic mutations from 4,645\ whole-genome and 19,184\ exome sequences that encompass most types of cancer. We identified 49\ single-base-substitution, 11\ doublet-base-substitution, 4\ clustered-base-substitution and 17\ small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

}, doi = {10.1038/s41586-020-1943-3}, author = {Alexandrov, Ludmil B and Kim, Jaegil and Haradhvala, Nicholas J and Huang, Mi Ni and Tian Ng, Alvin Wei and Wu, Yang and Boot, Arnoud and Covington, Kyle R and Gordenin, Dmitry A and Bergstrom, Erik N and Islam, S M Ashiqul and Lopez-Bigas, Nuria and Klimczak, Leszek J and McPherson, John R and Morganella, Sandro and Sabarinathan, Radhakrishnan and Wheeler, David A and Mustonen, Ville and Getz, Gad and Rozen, Steven G and Stratton, Michael R and PCAWG} } @article {82602, title = {Resource plasticity-driven carbon-nitrogen budgeting enables specialization and division of labor in a clonal community }, journal = {Elife}, volume = {9}, year = {2020}, month = {09/2020}, abstract = {

Previously, we found that in glucose-limited Saccharomyces cerevisiae colonies, metabolic constraints drive cells into groups exhibiting gluconeogenic or glycolytic states. In that study, threshold amounts of trehalose - a limiting, produced carbon-resource, controls the emergence and self-organization of cells exhibiting the glycolytic state, serving as a carbon source that fuels glycolysis (Varahan et al., 2019). We now discover that the plasticity of use of a non-limiting resource, aspartate, controls both resource production and the emergence of heterogeneous cell states, based on differential metabolic budgeting. In gluconeogenic cells, aspartate is a carbon source for trehalose production, while in glycolytic cells using trehalose for carbon, aspartate is predominantly a nitrogen source for nucleotide synthesis. This metabolic plasticity of aspartate enables carbon-nitrogen budgeting, thereby driving the biochemical self-organization of distinct cell states. Through this organization, cells in each state exhibit true division of labor, providing growth/survival advantages for the whole community.

}, doi = {10.7554/eLife.57609 }, author = {Varahan, Sriram and Sinha, Vaibhhav and Walvekar, Adhish and Krishna, Sandeep and Laxman, Sunil} } @article {79807, title = {RNA Blot Analysis for the Detection and Quantification of Plant MicroRNAs.}, journal = {J Vis Exp}, year = {2020}, month = {2020 Jul 11}, abstract = {

MicroRNAs (miRNAs) are a class of endogenously expressed non-coding, ~21 nt small RNAs involved in the regulation of gene expression in both plants and animals. Most miRNAs act as negative switches of gene expression targeting key genes. In plants, primary miRNAs (pri-miRNAs) transcripts are generated by RNA polymerase II, and they form varying lengths of stable stem-loop structures called pre-miRNAs. An endonuclease, Dicer-like1, processes the pre-miRNAs into miRNA-miRNA* duplexes. One of the strands from miRNA-miRNA* duplex is selected and loaded onto Argonaute 1 protein or its homologs to mediate the cleavage of target mRNAs. Although miRNAs are key signaling molecules, their detection is often carried out by less than optimal PCR-based methods instead of a sensitive northern blot analysis. We describe a simple, reliable, and extremely sensitive northern method that is ideal for the quantification of miRNA levels with very high sensitivity, literally from any plant tissue. Additionally, this method can be used to confirm the size, stability and the abundance of miRNAs and their precursors.

}, issn = {1940-087X}, doi = {10.3791/61394}, author = {Tirumalai, Varsha and Prasad, Melvin and Shivaprasad, P V} } @article {72071, title = {The role of geography, environment, and genetic divergence on the distribution of pikas in the Himalaya}, journal = {ECOLOGY AND EVOLUTION}, year = {2020}, month = {01/2020}, abstract = {

Pikas (Ochotona Link, 1795) are high-altitude specialist species making them a useful bioindicator species to warming in high-altitude ecosystem. The Himalayan Mountains are an important part of their range, supporting approximately 23\%{\textendash}25\% of total pika species worldwide, yet we lack basic information on the distribution patterns. We combine field-based surveys with genetics-based identification and phylogeny to identify differences in species-environment relationships. Further, we suggest putative evolutionary causes for the observed niche patterns.

}, doi = {10.1002/ece3.6007}, author = {Dahal, Nishma and Kumar, Sunil and Noon, Barry R and Nayak, Rajat and Lama, Rinzin Phunjok and Ramakrishnan, Uma} } @article {84574, title = {Role of RAB5 GEF in maintaining potassium levels under sodium chloride stress.}, journal = {Plant Direct}, volume = {4}, year = {2020}, month = {2020 Oct}, pages = {e00273}, abstract = {

Salt stress is one of the major factors impacting crop productivity worldwide. Through a variety of effector and signaling pathways, plants achieve survival under salinity stress by maintaining high cytosolic potassium/sodium ion (K/Na) ratios, preventing Na cytotoxicity, and retaining osmotic balance. Ras-related protein 5 (Rab5) members are involved in the trafficking of endosomes to the vacuole or plasma membrane (PM). The vacuolar protein sorting- associated protein 9 () encodes the single guanine nucleotide exchange factor (GEF) that activates all three known Rab5 proteins in . Previous work from our group has reported the critical function of for the operation of salt-induced endocytic pathway, as well as the expansion of endomembrane compartments under saline stress conditions. Here we show an additional role of in plant response to salt stress via maintenance of K status of the cell rather than Na homeostasis. Our results show that roots from mutant, subjected to 100\ mM NaCl, display alterations in transcript levels of genes involved in the K homeostasis pathway. Concurrent with the observed sensitivity of mutant under NaCl stress, exposure to low K environments resulted in growth retardation, and reduced rate of endocytosis. Furthermore, mutant displays reduced expression of auxin reporter, Direct Repeat-5 (DR5), and alterations in polarity and abundance of auxin efflux carrier PIN- FORMED2 (PIN2). Imposition of NaCl stress was found to be restrictive to the elongation capacity of cells in the root elongation zone of mutant. Together our results indicate that alterations in K homeostasis and associated cellular changes causing increased cell wall pH, contribute to diminished root growth and compromised survival of mutant under salt stress conditions.

}, issn = {2475-4455}, doi = {10.1002/pld3.273}, author = {Rajagopal, Divya and Mathew, M K} } @article {85903, title = {The same stress has divergent effects on social versus asocial manifestations of anxiety-like behavior over time.}, journal = {Stress}, year = {2020}, month = {2020 Nov 25}, pages = {1-21}, abstract = {

Stress may lead to augmented anxiety, which may, with time culminate in some form of anxiety disorder. Behavioral alterations related to increased anxiety can be broadly classified into two types - social, affecting interactions between individuals, and self-oriented, affecting the anxious individual only. While a growing body of literature now exists describing the effects of stress-induced anxiety on self-oriented behavior in animal models of anxiety disorders, the effects of such aberrant anxiety on social behavior has largely remained uncharacterized in these models. This study aims to fill this gap in our understanding by examining changes in social behavior following a single 2-hour episode of immobilization stress, which has been shown to cause delayed structural and functional changes in the amygdala. To this end, we examined social behavior, measured as active social interactions, anogenital sniffing, nose-to-nose contacts, allogrooming, actively following and crawling under, as well as self-oriented asocial behavior, manifested as self-grooming and rearing, in adult male rats. Stressed animals showed reduced social interaction 1 day after immobilization stress and this decrease was persistent for at least 10 days after stress. In contrast, individualistic behaviors were impaired only 10 days, but not 1 day later. Together, these results not only show that the same single episode of stress can elicit divergent effects on social and asocial measures of anxiety in the same animal, but also suggest that enhanced social anxiety soon after stress may also serve as an early indicator of its delayed behavioral effects.

}, issn = {1607-8888}, doi = {10.1080/10253890.2020.1855421}, author = {Saxena, Kapil and Chakraborty, Prabahan and Chattarji, Sumantra} } @article {82362, title = {Sarcopterygian fin ontogeny elucidates the origin of hands with digits.}, journal = {Sci Adv}, volume = {6}, year = {2020}, month = {2020 Aug}, pages = {eabc3510}, abstract = {

How the hand and digits originated from fish fins during the Devonian fin-to-limb transition remains unsolved. Controversy in this conundrum stems from the scarcity of ontogenetic data from extant lobe-finned fishes. We report the patterning of an autopod-like domain by during fin development of the Australian lungfish, the most closely related extant fish relative of tetrapods. Differences from tetrapod limbs include the absence of digit-specific expansion of and and distal limitation of and , which potentially evolved through an enhanced response to signaling in limbs. These developmental patterns indicate that the digit program originated in postaxial fin radials and later expanded anteriorly inside of a preexisting autopod-like domain during the evolution of limbs. Our findings provide a genetic framework for the transition of fins into limbs that supports the significance of classical models proposing a bending of the tetrapod metapterygial axis.

}, issn = {2375-2548}, doi = {10.1126/sciadv.abc3510}, author = {Woltering, Joost M and Irisarri, Iker and Ericsson, Rolf and Joss, Jean M P and Sordino, Paolo and Meyer, Axel} } @article {87963, title = {Satish Dhawan: The transformation of the Indian Institute of Science, Bangalore}, journal = {CURRENT SCIENCE}, volume = {119}, year = {2020}, month = {11/2020}, pages = {1427-1432}, doi = {10.18520/cs/v119/i9/1427-1432}, author = {Balaram, P} } @article {79802, title = {SEPT7 regulates Ca entry through Orai channels in human neural progenitor cells and neurons.}, journal = {Cell Calcium}, volume = {90}, year = {2020}, month = {2020 Jul 09}, pages = {102252}, abstract = {

Human neural progenitor cells (hNPCs) are self-renewing cells of neural lineage that can be differentiated into neurons of different subtypes. Here we show that SEPT7, a member of the family of filament-forming GTPases called septins, prevents constitutive Ca entry through the store-operated Ca entry channel, Orai in hNPCs and in differentiated neurons and is thus required for neuronal calcium homeostasis. Previous work in Drosophila neurons has shown that loss of one copy of the evolutionarily-conserved dSEPT7 gene leads to elevated Ca entry via Orai, in the absence of ER-Ca store depletion. We have identified an N-terminal polybasic region of SEPT7, known to interact with membrane-localized phospholipids, as essential for spontaneous calcium entry through Orai in hNPCs, whereas the GTPase domain of dSEPT7 is dispensable for this purpose. Re-organisation of Orai1 and the ER-Ca sensor STIM1 observed near the plasma membrane in SEPT7 KD hNPCs, supports the idea that Septin7 containing heteromers prevent Ca entry through a fraction of STIM-Orai complexes. Possible mechanisms by which SEPT7 reduction leads to opening of Orai channels in the absence of store-depletion are discussed.

}, issn = {1532-1991}, doi = {10.1016/j.ceca.2020.102252}, author = {Deb, Bipan K and Chakraborty, Pragnya and Gopurappilly, Renjitha and Hasan, Gaiti} } @article {86451, title = {Serotonin 2A (5-HT2A) receptor affects cell-matrix adhesion and the formation and maintenance of stress fibers in HEK293 cells.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {12/2020}, pages = {21675}, abstract = {

5-HT2A, a G-protein coupled receptor, is widely expressed in the human body, including in the gastrointestinal tract, platelets and the nervous system. It mediates various functions, for e.g. learning, memory, mood regulation, platelet aggregation and vasoconstriction, but its involvement in cell-adhesion remains largely unknown. Here we report a novel role for 5-HT2A in cell-matrix adhesion.In HEK293 cells, which are loosely adherent, expression and stimulation of human or rat 5-HT2A receptor by agonists such as serotonin or 2,5-dimethoxy-4-iodoamphetamine (DOI) led to a significant increase in adhesion, while inhibition of 5-HT2A by antipsychotics, such as risperidone, olanzapine or chlorpromazine prevented it. 5-HT2A activation gave rise to stress fibers in these cells and was also required for their maintenance. Mechanistically, the 5-HT2A-mediated adhesion was mediated by downstream PKC and Rho signaling. Since 5-HT2A is associated with many disorders such as dementia, depression and schizophrenia, its role in cell-matrix adhesion could have implications for neural circuits.

}, doi = {10.1038/s41598-020-78595-6}, author = {John Jayakumar JAK and Panicker, MM and Basu, B} } @article {73043, title = {A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency}, journal = {Elife}, year = {2020}, month = {01/2020}, chapter = {e52656}, abstract = {

SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walkup et al., 2016). For example, the ratio to PSD-95 of Transmembrane AMPA-Receptor-associated Proteins (TARPs), which mediate binding of AMPA-type glutamate receptors to PSD-95, was increased in young Syngap1+/-mice. Here we show that only females and not males show a highly significant correlation between an increase in TARP and a decrease in synGAP in the PSDs of Syngap1+/-rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency.

}, doi = {10.7554/eLife.52656}, author = {Mastro, TL and Preza, A and Basu, S and Chattarji, S and Till, SM and Kind, PC and Kennedy, MB} } @article {78102, title = {Sex-specific molecular specialization and activity rhythm dependent gene expression in honey bee antennae.}, journal = {J Exp Biol}, year = {2020}, month = {2020 May 11}, abstract = {

We performed an RNA-seq based comparison of gene expression levels in the antennae of honey bee drones and time-trained foragers (workers) collected at different times of the day and different activity states. Interestingly, olfaction-related genes (i.e. odorant receptor (), odorant binding proteins (), carboxyl esterases () etc.) showed stable gene expression differences between drone and worker antennae. Drone antennae showed higher expression of 24 of which 21 belong to the clade X which comprises the receptor for the major queen pheromone compound 9-ODA. This high number of drone-biased suggests that more than previously expected play a role in sex-pheromone communication. In addition, we found higher expression levels for many non-olfaction related genes including (), and the potassium channel In contrast, workers showed higher expression of 67 which belong to different clades that are involved in pheromone communication as well as the perception of cuticular hydrocarbons and floral scents. Further, drone antennae showed higher expression of genes involved in energy metabolism, whereas worker antennae showed higher expression of genes involved in neuronal communication consistent with earlier reports on peripheral olfactory plasticity. Finally, drones that perform mating flight in the afternoon (innate) and foragers that are trained to forage in the afternoon (adapted) showed similar daily changes in the expression of two major clock genes, and Most of the other genes showing changes with time or onset of daily flight activity were specific to drones and foragers.

}, issn = {1477-9145}, doi = {10.1242/jeb.217406}, author = {Jain, Rikesh and Brockmann, Axel} } @article {85849, title = {Similarities in dance follower behaviour across honey bee species suggest a conserved mechanism of dance communication}, journal = {ANIMAL BEHAVIOUR}, volume = {169}, year = {2020}, month = {11/2020}, pages = {139-155}, abstract = {

Social communication systems are predominantly multimodal and can combine modulatory and information-bearing signals. The honey bee waggle dance, one of the most elaborate forms of social communication in animals, activates nestmates to search for food and communicates symbolic information about the location of the food source. Previous studies on the dance behaviour in diverse honey bee species demonstrated distinct differences in the concurrence of visual, auditory, olfactory and tactile signals produced by the dancer. We studied the behaviour of dance signal receivers, the dance followers, to explore the potential significance of different signals in the communication process. In particular, we asked whether the behaviour of dance followers differs between the three major Asian honey bee species, Apis florea, Apis dorsata and Apis cerana, and whether this might correlate with the differences in the signals produced by the dancing foragers. Our comparison demonstrated that the behaviour of the dance followers is highly similar across all three species. The mean body orientation of the dance followers with respect to the waggle dancer was close to 90 degrees throughout the run, with the majority positioning themselves lateral to the dancer. These findings suggest that the communication of spatial information might be more conserved than implied by the differences in the signals produced by the dancer. Along with studies in Apis mellifera, our results suggest that all honey bee species rely on tactile contacts between the dancer and follower to communicate spatial information. The cues and signals that differ between the species may be involved in attracting the followers towards the dancer or increasing their motivation to start foraging in the different nest environments. (C) 2020 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

}, doi = {10.1016/j.anbehav.2020.09.011}, author = {George, Ebi Antony and Pimplikar, Smruti and Thulasi, Neethu and Brockmann, Axel} } @article {77445, title = {A socio-economic survey of the Singchung Bugun Village Community Reserve, Arunachal Pradesh, India}, journal = {CURRENT SCIENCE}, volume = {118}, year = {2020}, month = {05/2020}, pages = {1415-1419}, abstract = {

Community-managed lands often lack vital baseline information that assesses both natural resource dependence, as well as perceptions of power, involvement and support in management. We interviewed 171 households from 16 villages in the buffer of the Sin chung Bugun Village Community Reserve (SBVCR) in Arunachal Pradesh, India. In total, 68\% stated that SBVCR would be beneficial to wildlife and in terms of ecosystem services, and 45\% expressed support for its formation. However, 76\% identified multiple threats to the Reserve, including forest fires, hunting and agricultural expansion. Different parts of the Reserve were identified as being important for resource extraction, non-extractive uses and the need to be disturbance-free (with varying overlaps across these areas), thus calling for adaptive management.

}, doi = {10.18520/cs/v118/i9/1415-1419}, author = {Borah, B and Velho, N and Srinivasan, U} } @article {81664, title = {Stability of Begomoviral pathogenicity determinant βC1 is modulated by mutually antagonistic SUMOylation and SIM interactions.}, journal = {BMC Biol}, volume = {18}, year = {2020}, month = {2020 Aug 31}, pages = {110}, abstract = {

BACKGROUND: To successfully invade new hosts, plant viruses must break host resistance and be competent to move within and between plant cells. As a means, viral proteins known as pathogenicity determinants have evolved to coordinate a network of protein interactions. The βC1 protein encoded by specific geminiviral satellites acts as a key pathogenicity determinant for this disease-causing family of plant viruses. Post-translational modifications (PTMs) such as ubiquitination and phosphorylation of the βC1 protein have been shown to occur in diverse viruses. However, the relevance of these and other layers of PTMs in host-geminiviral interactions has not been fully understood.

RESULTS: Here we identified the significance of a novel layer of PTMs in the βC1 protein of Synedrella yellow vein clearing virus (SyYVCV), a newly identified member of the Begomovirus genus of Geminiviruses. This protein has conserved SUMOylation and SUMO-interacting motifs (SIMs), and we observed SUMOylation of SyYVCV βC1 in host plants as a defensive strategy against ubiquitin-mediated degradation. Counteracting this, SIMs encoded in βC1 mediate the degradation of βC1; however, both these PTMs are essential for the function of βC1 protein since SIM and SUMOylation motif mutants failed to promote pathogenicity and viral replication in vivo. SUMOylation in different motifs of βC1 led to functionally distinct outcomes, regulating the stability and function of the βC1 protein, as well as increased global SUMOylation of host proteins.

CONCLUSION: Our results indicate the presence of a novel mechanism mediating a fine balance between defence and counter-defence in which a SIM site is competitively sought for degradation and, as a counter-defence, βC1 undergoes SUMOylation to escape from its degradation.

}, issn = {1741-7007}, doi = {10.1186/s12915-020-00843-y}, author = {Nair, Ashwin and Chatterjee, Kiran Sankar and Jha, Vikram and Das, Ranabir and Shivaprasad, P V} } @article {80777, title = {A strategic road map for conserving the Endangered dhole Cuon alpinus in India}, journal = {MAMMAL REVIEW}, year = {2020}, month = {07/2020}, abstract = {

1. Large carnivores face high extinction risks, often exacerbated by the absence of adequate information on their ecological requirements, and the high economic and socio-political commitments that their conservation warrants. Country-scale conservation plans can serve as effective frameworks to prioritise areas, actions, and conservation investments.

2. We explore conservation tenets of retention, recovery, and restoration for the Endangered dholeCuon alpinusin India - a global stronghold for the species. Specifically, we: 1) examine the current status of dholes in India{\textquoteright}s states using a recent distribution assessment; 2) identify areas for directing management interventions - zones to be targeted for population recovery and for habitat recovery; 3) identify potential areas for range expansion; 4) use eco-socio-political criteria to determine state-wise conservation priority scores and likelihood of conservation action; and 5) conduct an exhaustive review of all published literature on dholes.

3. Dholes occupy similar to 49\% of potential habitats in 685 of mainland India{\textquoteright}s 2342 sub-districts. We identified 143 sub-districts with potential for dhole population recovery, 145 for habitat recovery, and 404 for range expansion. Of the 34 mainland states/union territories, 17 were identified as high priority for dhole conservation. Of these, nine are adequately equipped to implement management actions to conserve dholes, while eight need to improve capacity towards increasing likelihood of conservation success.

4. Literature on dholes (from 1874 to 2019;n=237) was dominated by natural history notes, followed by distribution records and studies of population ecology. A majority of the reviewed studies were from India (55\% of 215 country-specific papers). The number of studies showed an exponential increase over time: 43\% were published in the last decade.

5. Our review of published literature revealed significant knowledge gaps in terms of quantitative ecological assessments across all dhole range-countries. Given this context, our results provide a comprehensive, multi-dimensional, and administratively feasible road map for dhole conservation in India, with potential applicability in other dhole range-countries and also for other threatened species.

}, doi = {10.1111/mam.12209}, author = {Srivathsa, Arjun and Sharma, Sushma and Singh, Priya and Punjabi, Girish A. and Oli, Madan K.} } @article {78170, title = {Stratification relieves constraints from steric hindrance in the generation of compact actomyosin asters at the membrane cortex.}, journal = {Sci Adv}, volume = {6}, year = {2020}, month = {03/2020}, abstract = {

Recent in vivo studies reveal that several membrane proteins are driven to form nanoclusters by active contractile flows arising from localized dynamic patterning of F-actin and myosin at the cortex. Since myosin-II assemble as minifilaments with tens of myosin heads, one might worry that steric considerations would obstruct the emergence of nanoclustering. Using coarse-grained, agent-based simulations that account for steric constraints, we find that the patterns exhibited by actomyosin in two dimensions, do not resemble the steady-state patterns in our in vitro reconstitution of actomyosin on a supported bilayer. We perform simulations in a thin rectangular slab, separating the layer of actin filaments from myosin-II minifilaments. This recapitulates the observed features of in vitro patterning. Using super resolution microscopy, we find evidence for such stratification in our in vitro system. Our study suggests that molecular stratification may be an important organizing feature of the cortical cytoskeleton in vivo.

}, doi = {10.1126/sciadv.aay6093}, author = {Das, A and Bhat, A and Sknepnek, R and K{\"o}ster, D and Mayor, S and Rao, M} } @article {70234, title = {Stress-induced modulation of endocannabinoid signaling leads to delayed strengthening of synaptic connectivity in the amygdala.}, journal = {Proc Natl Acad Sci U S A}, volume = {117}, year = {2020}, month = {2019 Dec 16}, pages = {650-655}, abstract = {

Even a brief exposure to severe stress strengthens synaptic connectivity days later in the amygdala, a brain area implicated in the affective symptoms of stress-related psychiatric disorders. However, little is known about the synaptic signaling mechanisms during stress that eventually culminate in its delayed impact on the amygdala. Hence, we investigated early stress-induced changes in amygdalar synaptic signaling in order to prevent its delayed effects. Whole-cell recordings in basolateral amygdala (BLA) slices from rats revealed higher frequency of miniature excitatory postsynaptic currents (mEPSCs) immediately after 2-h immobilization stress. This was replicated by inhibition of cannabinoid receptors (CBR), suggesting a role for endocannabinoid (eCB) signaling. Stress also reduced -arachidonoylethanolamine (AEA), an endogenous ligand of CBR. Since stress-induced activation of fatty acid amide hydrolase (FAAH) reduces AEA, we confirmed that oral administration of an FAAH inhibitor during stress prevents the increase in synaptic excitation in the BLA soon after stress. Although stress also caused an immediate reduction in synaptic inhibition, this was not prevented by FAAH inhibition. Strikingly, FAAH inhibition during the traumatic stressor was also effective 10 d later on the delayed manifestation of synaptic strengthening in BLA neurons, preventing both enhanced mEPSC frequency and increased dendritic spine-density. Thus, oral administration of an FAAH inhibitor during a brief stress prevents the early synaptic changes that eventually build up to hyperexcitability in the amygdala. This framework is of therapeutic relevance because of growing interest in targeting eCB signaling to prevent the gradual development of emotional symptoms and underlying amygdalar dysfunction triggered by traumatic stress.

}, issn = {1091-6490}, doi = {10.1073/pnas.1910322116}, author = {Yasmin, Farhana and Colangeli, Roberto and Morena, Maria and Filipski, Sarah and van der Stelt, Mario and Pittman, Quentin J and Hillard, Cecilia J and Teskey, G Campbell and McEwen, Bruce S and Hill, Matthew N and Chattarji, Sumantra} } @article {79728, title = {Structural insights into actin filament recognition by commonly used cellular actin markers}, journal = {EMBO J}, volume = {39}, year = {2020}, month = {07/2020}, abstract = {

Cellular studies of filamentous actin (F-actin) processes commonly utilize fluorescent versions of toxins, peptides, and proteins that bind actin. While the choice of these markers has been largely based on availability and ease, there is a severe dearth of structural data for an informed judgment in employing suitable F-actin markers for a particular requirement. Here, we describe the electron cryomicroscopy structures of phalloidin, lifeAct, and utrophin bound to F-actin, providing a comprehensive high-resolution structural comparison of widely used actin markers and their influence towards F-actin. Our results show that phalloidin binding does not induce specific conformational change and lifeAct specifically recognizes closed D-loop conformation, i.e., ADP-Pi or ADP states of F-actin. The structural models aided designing of minimal utrophin and a shorter lifeAct, which can be utilized as F-actin marker. Together, our study provides a structural perspective, where the binding sites of utrophin and lifeAct overlap with majority of actin-binding proteins and thus offering an invaluable resource for researchers in choosing appropriate actin markers and generating new marker variants.

}, doi = {10.15252/embj.2019104006 }, author = {Kumari, Archana and Kesarwani, Shubham and Javoor, Manjunath G and Vinothkumar, Kutti R and Sirajuddin, Minhajuddin} } @article {86518, title = {Structure and Function of -Acetylmannosamine Kinases from Pathogenic Bacteria.}, journal = {ACS Omega}, volume = {5}, year = {2020}, month = {2020 Dec 08}, pages = {30923-30936}, abstract = {

Several pathogenic bacteria import and catabolize sialic acids as a source of carbon and nitrogen. Within the sialic acid catabolic pathway, the enzyme -acetylmannosamine kinase (NanK) catalyzes the phosphorylation of -acetylmannosamine to -acetylmannosamine-6-phosphate. This kinase belongs to the ROK superfamily of enzymes, which generally contain a conserved zinc-finger (ZnF) motif that is important for their structure and function. Previous structural studies have shown that the ZnF motif is absent in NanK of (-NanK), a Gram-negative bacterium that causes the gum disease gingivitis. However, the effect in loss of the ZnF motif on the kinase activity is unknown. Using kinetic and thermodynamic studies, we have studied the functional properties of -NanK to its substrates ManNAc and ATP, compared its activity with other ZnF motif-containing NanK enzymes from closely related Gram-negative pathogenic bacteria (-NanK), (-NanK), and (-NanK). Our studies show a 10-fold decrease in substrate binding affinity between NanK (apparent ≈ 700 μM) and ZnF motif-containing NanKs (apparent ≈ 60 μM). To understand the structural features that combat the loss of the ZnF motif in -NanK, we solved the crystal structures of functionally homologous ZnF motif-containing NanKs from and . Here, we report -NanK:unliganded, -NanK:AMPPNP, -NanK:ManNAc, -NanK:ManNAc, and -NanK:ManNAc-6P:ADP crystal structures. Structural comparisons of -NanK with -NanK, -NanK, and hMNK (human -acetylmannosamine kinase domain of UDP--acetylglucosamine-2-epimerase/-acetylmannosamine kinase, GNE) show that even though there is less sequence identity, they have high degree of structural similarity. Furthermore, our structural analyses highlight that the ZnF motif of -NanK is substituted by a set of hydrophobic residues, which forms a hydrophobic cluster that helps the proper orientation of ManNac in the active site. In summary, ZnF-containing and ZnF-lacking NanK enzymes from different Gram-negative pathogenic bacteria are functionally very similar but differ in their metal requirement. Our structural studies unveil the structural modifications in -NanK that compensate the loss of the ZnF motif in comparison to other NanK enzymes.

}, issn = {2470-1343}, doi = {10.1021/acsomega.0c03699}, author = {Gangi Setty, Thanuja and Sarkar, Arunabha and Coombes, David and Dobson, Renwick C J and Subramanian, Ramaswamy} } @article {67834, title = {Successes and challenges in simulating the folding of large proteins.}, journal = {J Biol Chem}, volume = {295}, year = {2020}, month = {2019 Nov 11}, pages = {15-33}, abstract = {

Computational simulations of protein folding can be used to interpret experimental folding results, to design new folding experiments and to test the effects of mutations and small molecules on folding. However, while major experimental and computational progress has been made in understanding how small proteins fold, research on larger, multi-domain proteins, which comprise the majority of proteins, is less advanced. Specifically, large proteins often fold via long-lived partially folded intermediates, whose structures, potentially toxic oligomerization and interactions with cellular chaperones remain poorly understood. Molecular dynamics (MD) based folding simulations that rely on knowledge of the native structure can provide critical, detailed information on folding free energy landscapes, intermediates and pathways. Further, increases in computational power and methodological advances have made folding simulations of large proteins practical and valuable. Here, using serpins that inhibit proteases as an example, we review native-centric methods for simulating the folding of large proteins. These synergistic approaches range from Go and related structure-based models (SBMs) that can predict the effects of the native structure on folding to all-atom-based methods that include side chain chemistry and can predict how disease-associated mutations may impact folding. The application of these computational approaches to serpins and other large proteins highlights the successes and limitations of current computational methods and underscores how computational results can be used to inform experiments. These powerful simulation approaches in combination with experiments can provide unique insights into how large proteins fold and misfold expanding our ability to predict and manipulate protein folding.

}, issn = {1083-351X}, doi = {10.1074/jbc.REV119.006794}, author = {Gershenson, Anne and Gosavi, Shachi and Faccioli, Pietro and Wintrode, Patrick L} } @article {79797, title = {Surviving nutritional deprivation during development: neuronal intracellular calcium signaling is critical.}, journal = {Int J Dev Biol}, volume = {64}, year = {2020}, month = {2020}, pages = {249-256}, abstract = {

Developing cells and tissues in a growing animal need to sense food quality and integrate this information with on-going time-bound developmental programs. The integration of metabolism with development requires cellular and systemic coordination. Work in our laboratory has focused on Ca signaling arising from the release of Ca stored in the endoplasmic reticulum (ER), which triggers store-operated Ca entry. We describe a role for ER-store Ca that operates at the cellular level in various classes of neurons, and eventually drives the systemic coordination required to survive and complete development under conditions of nutritional deprivation. In the model system Drosophila melanogaster, we have developed a paradigm to induce nutritional stress during the larval stage and used pupariation as a read-out for development. Applying the vast genetic tool kit available in Drosophila to this paradigm, we have uncovered novel roles for intracellular Ca signaling in regulating neuronal activity, at the level of transcription in glutamatergic neurons, and translation in neuropeptidergic neurons. We find that such regulation of cellular processes is critical for integrating information across a neural circuit at multiple levels, starting from the point of sensing systemic and environmental levels of amino acids to finally connecting with neuropeptide secreting neurons, that communicate with the prothoracic gland, an organ that makes the key developmental hormone, ecdysone. This work underscores the importance of ER-store Ca for neuronal health, with consequences for animal development.

}, issn = {1696-3547}, doi = {10.1387/ijdb.190148mm}, author = {Hasan, Gaiti} } @article {81590, title = {On the systematic status of Calliophis macclellandi nigriventer Wall, 1908 (Reptilia: Serpentes: Elapidae)}, journal = {ZOOTAXA}, volume = {4821}, year = {2020}, month = {07/2020}, pages = {105-120}, abstract = {

Sinomicrurus macclellandi (Reinhardt, 1844) is a species of coral snakes distributed across the forests of Southeast Asia and the Himalayas. The species exhibits distinct forms across its range, and it has been classified into four subspecies. Calliophis macclellandi nigriventer Wall, 1908 a population from Western Himalayas, which was described as a variety, has not been attended to until now. Our study of a recently collected specimen from near Solan, Himachal Pradesh, India and existing museum material has allowed us to assess the validity of this population based on molecular and morphological data and has given us enough evidence to suggest its elevation to a species rank. Sinomicrurus nigriventer comb. nov. was found to be embedded within a clade comprising S. peinani, but not S. macclellandi s. l., with a genetic distance of 7-16\% from its congeners. Morphologically, it differs from its congeners in having a reddish brown dorsum and a mid-dorsal black vertebral strip extending from the nape to the vent and with three thin bands on the tail, belly white with black smear up to the vent, tail dorsum with a few band-like blotches, and males with 230-235 ventral scales.

}, doi = {10.11646/zootaxa.4821.1.5}, author = {Mirza, Zeeshan A and Varma, Vishal and Campbell, Patrick D.} } @article {92430, title = {Targeting Toll like Receptors in Cancer: Role of TLR Natural and Synthetic Modulators}, journal = {Curr Pharm Des}, volume = {26}, year = {2020}, month = {10/2020}, pages = {5040-5053}, abstract = {

Background: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the broad class pattern recognition receptors (PRR), involved in recognition of Pathogen Associated Molecular Patterns (PAMPs) thereby inducing an immune response. Apart from these exogenous PAMPs, numerous endogenous PAMPs are also ligands for various TLRs thereby activating the TLR dependent immune response, subsequently leading to the onset of an inflammatory response. Prolonged activation of TLR by these endogenous PAMPs leads to chronic inflammatory insults to the body and which in turn alters the proliferative patterns of the cells, which ultimately leads to the development of cancer.

Objectives: The present review aims to provide a detailed outline of the differential roles of various TLRs in cancer and the possible use of them as a therapeutic target.

Methods: Data were collected from PubMed/Sciencedirect/Web of Science database and sorted; the latest literature on TLRs was incorporated in the review.

Results: Among the different TLRs, few are reported to be anti-neoplastic, which controls the cell growth and multiplication in response to the endogenous signals. On the contrary, numerous studies have reported the procarcinogenic potentials of TLRs. Hence, TLRs have emerged as a potential target for the prevention and treatment of various types of cancers. Several molecules, such as monoclonal antibodies, small molecule inhibitors and natural products have shown promising anticancer potential by effectively modulating the TLR signalling.

Conclusion: Toll-like receptors play vital roles in the process of carcinogenesis, hence TLR targeting is a promising approach for cancer prevention.

}, doi = {10.2174/1381612826666200720235058}, author = {Narayanankutty, A and Sasidharan, A and Job, JT} } @article {84066, title = {Three new species of Protosticta Selys, 1885 (Odonata: Zygoptera: Platystictidae) from the Western Ghats, India, with taxonomic notes on P. mortoni Fraser, 1922 and rediscovery of P. rufostigma Kimmins, 1958.}, journal = {Zootaxa}, volume = {4858}, year = {2020}, month = {2020 Sep 30}, pages = {zootaxa.4858.2.1}, abstract = {

Three new species of Protosticta Selys, 1885 (Odonata: Zygoptera: Platystictidae) from the Western Ghats biodiversity hotspot in India: P. cyanofemora sp. nov. (wet evergreen forests in Shendurney Wildlife Sanctuary, Kollam, Kerala and Kalakkad Mundanthurai Tiger Reserve, Tirunelveli, Tamil Nadu), P. myristicaensis sp. nov. (Myristica swamp at Kathalekan, Shivamogga, Karnataka) and P. sholai sp. nov. (montane sholas of Upper Manalar, Meghamalai Wildlife Sanctuary, Theni, Tamil Nadu) are described and illustrated. We compare these three new species with other Protosticta spp. from the Western Ghats based on new material and provide comprehensive differential diagnoses with determination key for males of all species occurring in the Western Ghats. The taxonomic validity of P. mortoni Fraser, 1922 is established with fresh specimens from Hassan, Karnataka, and rediscovery of P. rufostigma Kimmins, 1958 is reported from Kanyakumari Wildlife Sanctuary, Tamil Nadu.

}, keywords = {Animals, Animals, Wild, Biodiversity, Forests, India, Male, Odonata}, issn = {1175-5334}, doi = {10.11646/zootaxa.4858.2.1}, author = {Joshi, Shantanu and Subramanian, K A and Babu, R and Sawant, Dattaprasad and Kunte, Krushnamegh} } @article {87962, title = {Tigers against the odds: Applying macro-ecology to species recovery in India}, journal = {BIOLOGICAL CONSERVATION}, year = {2020}, month = {12/2020}, pages = {Article No. 108846}, abstract = {

Tigers are in serious decline from anthropogenic pressures: prey depletion by human hunting, killing of tigers for conflict mitigation or trade in their body parts, and habitat loss or degradation. In spite of conservation efforts over 50 years, wild tigers now occupy \<7\% of their historic range. Reproducing tiger populations survive in \<1\% of the similar to 1.6 million km(2) potential habitat. Evaluating both successful and failed conservation efforts is critical to reversing tiger declines. Wild tiger populations are managed by governments under constraints imposed by other stake-holders. We review recoveries of tigers across a 38,000 km(2) area landscape matrix in Malenad region in southwestern India, during the past five decades. We examine data and empirical observations on tiger ecology, human impacts, emergent conflicts, as well as conservation interventions made at macro-ecological scales by the non-governmental project titled Malenad Tiger Program. We estimate that between 1970 and 2015, tiger habitat occupancy remained unchanged at 14,000 km(2), out of 21,000 km(2) of potential habitat in Malenad. However, tiger numbers rose from 70 to 391, only because of sporadic recoveries in a few wildlife reserves. We conclude that if tiger recovery efforts can be optimized in future, the Malenad landscape can potentially support 1300 wild tigers. We propose pragmatic strategies that may improve success rates and cost-effectiveness of future recovery efforts directed at tigers, and, generally at other threatened large carnivores. We evaluate both challenges and opportunities that non-governmental conservation programs must address to be effective in assisting tiger recoveries in the future.

}, doi = {10.1016/j.biocon.2020.108846}, author = {Karanth, UK and Kumar, Samba and Karanth, Krithi} } @article {83748, title = {Tissue-specific developmental regulation and isoform usage underlie the role of in sex differentiation and mimicry in swallowtails.}, journal = {R Soc Open Sci}, volume = {7}, year = {2020}, month = {2020 Sep}, pages = {200792}, abstract = {

Adaptive phenotypes often arise by rewiring existing developmental networks. Co-option of transcription factors in novel contexts has facilitated the evolution of ecologically important adaptations. () governs fundamental sex differentiation during embryonic stages and has been co-opted to regulate diverse secondary sexual dimorphisms during pupal development of holometabolous insects. In , regulates female-limited mimetic polymorphism, resulting in mimetic and non-mimetic forms. To understand how a critical gene such as regulates novel wing patterns while maintaining its basic function in sex differentiation, we traced its expression through metamorphosis in using developmental transcriptome data. We found three key expression peaks: (i) eggs in pre- and post-ovisposition stages; (ii) developing wing discs and body in final larval instar; and (iii) 3-day pupae. We identified potential targets using co-expression and differential expression analysis, and found distinct, non-overlapping sets of genes-containing putative binding sites-in developing wings versus abdominal tissue and in mimetic versus non-mimetic individuals. This suggests that regulates distinct downstream targets in different tissues and wing colour morphs and has perhaps acquired new, previously unknown targets, for regulating mimetic polymorphism. Additionally, we observed that the three female isoforms of were differentially expressed across stages (from eggs to adults) and tissues and differed in their protein structure. This may promote differential protein-protein interactions for each isoform and facilitate sub-functionalization of activity across its isoforms. Our findings suggest that employs tissue-specific downstream effectors and partitions its functions across multiple isoforms to regulate primary and secondary sexual dimorphism through insect development.

}, issn = {2054-5703}, doi = {10.1098/rsos.200792}, author = {Deshmukh, Riddhi and Lakhe, Dhanashree and Kunte, Krushnamegh} } @article {79791, title = {Tools of the trade: MicroCT reveals native structure and functional morphology of organs that drive caterpillar-ant interactions.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {2020 Jun 29}, pages = {10593}, abstract = {

Caterpillars of many lycaenid butterflies are tended by ants that offer protection from predators and parasitoids. Specialized structures such as glands, ciliary organs and chitinous ornamentation in caterpillars play key roles in the underlying tactile, acoustic, and chemical communication between caterpillars and ants. Although the ecological, evolutionary, and behavioural aspects of these interactions are well studied, the mechanisms (i.e., the functional morphology) that drive the specialized interactive organs are poorly characterized. We used advanced X-ray microtomography (MicroCT) to delineate internal, native morphology of specialized larval dew patches, nectar glands, and tactile ciliary organs that mediate interactions between Crematogaster ants and caterpillars of the obligate myrmecophilous Apharitis lilacinus butterfly. Our non-destructive MicroCT analysis provided novel 3-D insights into the native structure and positions of these specialized organs in unmatched detail. This analysis also suggested a functional relationship between organ structures and surrounding muscles and nervation that operate the glands and tactile organs, including a {\textquoteright}lasso bag{\textquoteright} control mechanism for dew patches and muscle control for other organs. This provided a holistic understanding of the organs that drive very close caterpillar-ant interactions. Our MicroCT analysis opens a door for similar structural and functional analysis of adaptive insect morphology.

}, issn = {2045-2322}, doi = {10.1038/s41598-020-67486-5}, author = {Basu, Dipendra Nath and Kunte, Krushnamegh} } @article {77439, title = {Toward a new picture of the living plasma membrane.}, journal = {Protein Sci}, volume = {29}, year = {2020}, month = {2020 Jun}, pages = {1355-1365}, abstract = {

Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In this model, the membrane, composed of over thousand lipid and protein species, is organized as a well-equilibrated two-dimensional fluid. Here, the distribution of lipids is largely expected to reflect a multicomponent system, and proteins are expected to be surrounded by an annulus of specialized lipid species. With the recognition that a multicomponent lipid membrane is capable of phase segregation, the membrane is expected to appear as patchwork quilt pattern of membrane domains. However, the constituents of a living membrane are far from being well equilibrated. The living cell membrane actively maintains a trans-bilayer asymmetry of composition, and its constituents are subject to a number of dynamic processes due to synthesis, lipid transfer as well as membrane traffic and turnover. Moreover, membrane constituents engage with the dynamic cytoskeleton of a living cell, and are both passively as well as actively manipulated by this engagement. The extracellular matrix and associated elements also interact with membrane proteins contributing to another layer of interaction. At the nano- and mesoscale, the organization of lipids and proteins emerge from these encounters, as well as from protein-protein, protein-lipid, and lipid-lipid interactions in the membrane. New methods to study the organization of membrane components at these scales have also been developed, and provide an opportunity to synthesize a new picture of the living cell surface as an active membrane composite.

}, issn = {1469-896X}, doi = {10.1002/pro.3874}, author = {Kalappurakkal, Joseph Mathew and Sil, Parijat and Mayor, Satyajit} } @article {57789, title = {The transcriptome enables the identification of candidate genes behind medicinal value of Drumstick tree (Moringa oleifera).}, journal = {Genomics}, volume = {112}, year = {2020}, month = {01/2020}, pages = {621-628}, abstract = {

Moringa oleifera is a plant well-known for its nutrition value, drought resistance and medicinal properties. cDNA libraries from five different tissues (leaf, root, stem, seed and flower) of M. oleifera cultivar Bhagya were generated and sequenced. We developed a bioinformatics pipeline to assemble transcriptome, along with the previously published M. oleifera genome, to predict 17,148 gene models. Few candidate genes related to biosynthesis of secondary metabolites, vitamins and ion transporters were identified. Expressions were further confirmed by real-time quantitative PCR experiments for few promising leads. Quantitative estimation of metabolites, as well as elemental analysis, was also carried out to support our observations. Enzymes in the biosynthesis of vitamins and metabolites like quercetin and kaempferol are highly expressed in leaves, flowers and seeds. The expression of iron transporters and calcium storage proteins were observed in root and leaves. In general, leaves retain the highest amount of small molecules of interest.

}, issn = {1089-8646}, doi = {10.1016/j.ygeno.2019.04.014}, author = {Pasha, Shaik Naseer and Shafi, K Mohamed and Joshi, Adwait G and Meenakshi, Iyer and Harini, K and Mahita, Jarjapu and Sajeevan, Radha Sivarajan and Karpe, Snehal D and Ghosh, Pritha and Nitish, Sathyanarayanan and Gandhimathi, A and Mathew, Oommen K and Prasanna, Subramanian Hari and Malini, Manoharan and Mutt, Eshita and Naika, Mahantesha and Ravooru, Nithin and Rao, Rajas M and Shingate, Prashant N and Sukhwal, Anshul and Sunitha, Margaret S and Upadhyay, Atul K and Vinekar, Rithvik S and Sowdhamini, Ramanathan} } @article {80094, title = {Transcriptomic profiling of the medicinal plant Clitoria ternatea: identification of potential genes in cyclotide biosynthesis.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {2020 Jul 29}, pages = {12658}, abstract = {

Clitoria ternatea a perennial climber of the Fabaceae family, is well known for its agricultural and medical applications. It is also currently the only known member of the Fabaceae family that produces abundant amounts of the ultra-stable macrocyclic peptides, cyclotides, across all tissues. Cyclotides are a class of gene-encoded, disulphide-rich, macrocyclic peptides (26-37 residues) acting as defensive metabolites in several plant species. Previous transcriptomic studies have demonstrated the genetic origin of cyclotides from the Fabaceae plant family to be embedded in the albumin-1 genes, unlike its counterparts in other plant families. However, the complete mechanism of its biosynthesis and the repertoire of enzymes involved in cyclotide folding and processing remains to be understood. In this study, using RNA-Seq data and de novo transcriptome assembly of Clitoria ternatea, we have identified 71 precursor genes of cyclotides. Out of 71 unique cyclotide precursor genes obtained, 51 sequences display unique cyclotide domains, of which 26 are novel cyclotide sequences, arising from four individual tissues. MALDI-TOF mass spectrometry analysis of fractions from different tissue extracts, coupled with precursor protein sequences obtained from transcriptomic data, established the cyclotide diversity in this plant species. Special focus in this study has also been on identifying possible enzymes responsible for proper folding and processing of cyclotides in the cell. Transcriptomic mining for oxidative folding enzymes such as protein-disulphide isomerases (PDI), ER oxidoreductin-1 (ERO1) and peptidylprolyl cis-trans isomerases (PPIases)/cyclophilins, and their levels of expression are also reported. In particular, it was observed that the CtPDI genes formed plant-specific clusters among PDI genes as compared to those from other plant species. Collectively, this work provides insights into the biogenesis of the medicinally important cyclotides and establishes the expression of certain key enzymes participating in peptide biosynthesis. Also, several novel cyclotide sequences are reported and precursor sequences are analysed in detail. In the absence of a published reference genome, a comprehensive transcriptomics approach was adopted to provide an overview of diverse properties and constituents of C. ternatea.

}, issn = {2045-2322}, doi = {10.1038/s41598-020-69452-7}, author = {Kalmankar, Neha V and Venkatesan, Radhika and Balaram, Padmanabhan and Sowdhamini, Ramanathan} } @article {71096, title = {Tree diversity and carbon storage cobenefits in tropical human-dominated landscapes}, journal = {Conservation Letters}, year = {2020}, month = {01/2020}, abstract = {

A lack of spatial congruence between carbon storage and biodiversity in intact forests suggests limited cobenefits of carbon-focused policies for conserving tropical biodiversity. However, whether the same applies in tropical human-dominated landscapes (HDLs) is unclear. In India{\textquoteright}s Western Ghats Biodiversity Hotspot, we found that while HDL forests harbor lower tree diversity and aboveground carbon stocks than relatively intact forests, positive diversity{\textendash}carbon correlations are more prevalent in HDLs. This is because anthropogenic drivers of species loss in HDLs consistently reduce carbon storing biomass volume (lower basal area), and biomass per unit volume (fewer hardwood trees). We further show, using a meta-analysis spanning multiple regions, that these patterns apply to tropical HDLs more generally. Thus, while complementary strategies are needed for securing the irreplaceable biodiversity and carbon values of intact forests, ubiquitous tropical HDLs might hold greater potential for synergizing biodiversity conservation and climate change mitigation.

}, doi = {10.1111/conl.12699}, author = {Osuri, A. M. and Machado, Siddarth and Ratnam, J. and Sankaran, M. and Ayyappan, N and Muthuramkumar, S and Parthasarathy, N and P{\'e}lissier, R and Ramesh, B R and DeFries, R and Naeem, S} } @article {82356, title = {Twist1 induces chromosomal instability (CIN) in colorectal cancer cells.}, journal = {Hum Mol Genet}, volume = {29}, year = {2020}, month = {2020 Jun 27}, pages = {1673-1688}, abstract = {

Twist1 is a basic helix-loop-helix transcription factor, essential during early development in mammals. While Twist1 induces epithelial-to-mesenchymal transition (EMT), here we show that Twist1 overexpression enhances nuclear and mitotic aberrations. This is accompanied by an increase in whole chromosomal copy number gains and losses, underscoring the role of Twist1 in inducing chromosomal instability (CIN) in colorectal cancer cells. Array comparative genomic hybridization (array CGH) analysis further shows sub-chromosomal deletions, consistent with an increased frequency of DNA double strand breaks (DSBs). Remarkably, Twist1 overexpression downmodulates key cell cycle checkpoint factors-Bub1, BubR1, Mad1 and Mad2-that regulate CIN. Mathematical simulations using the RACIPE tool show a negative correlation of Twist1 with E-cadherin and BubR1. Data analyses of gene expression profiles of patient samples from The Cancer Genome Atlas (TCGA) reveal a positive correlation between Twist1 and mesenchymal genes across cancers, whereas the correlation of TWIST1 with CIN and DSB genes is cancer subtype-specific. Taken together, these studies highlight the mechanistic involvement of Twist1 in the deregulation of factors that maintain genome stability during EMT in colorectal cancer cells. Twist1 overexpression enhances genome instability in the context of EMT that further contributes to cellular heterogeneity. In addition, these studies imply that Twist1 downmodulates nuclear lamins that further alter spatiotemporal organization of the cancer genome and epigenome. Notwithstanding their genetic background, colorectal cancer cells nevertheless maintain their overall ploidy, while the downstream effects of Twist1 enhance CIN and DNA damage enriching for sub-populations of aggressive cancer cells.

}, issn = {1460-2083}, doi = {10.1093/hmg/ddaa076}, author = {Khot, Maithilee and Sreekumar, Dyuthi and Jahagirdar, Sanika and Kulkarni, Apoorva and Hari, Kishore and Faseela, Elangoli Ebrahimkutty and Sabarinathan, Radhakrishnan and Jolly, Mohit Kumar and Sengupta, Kundan} } @article {78093, title = {Two more new Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae)~from Tamil Nadu, India.}, journal = {Zootaxa}, volume = {4729}, year = {2020}, month = {2020 Jan 29}, pages = {zootaxa.4729.2.6}, abstract = {

Two new species of the gekkonid genus Hemiphyllodactylus are described from mountains of the Western Ghats in Tamil Nadu, southern India. Hemiphyllodactylus nilgiriensis sp. nov. and H. peninsularis sp. nov. are \> 5 \% divergent in the mitochondrial ND2 gene from each other and members of the H. aurantiacus complex and differ from each other and members of the H. aurantiacus complex in several meristic characters and colouration. The description of these two new species takes the number of Indian Hemiphyllodactylus to six and the number of endemic geckos from Tamil Nadu to 15.

}, keywords = {Animals, Genes, Mitochondrial, India, Lizards, Phylogeny, Records}, issn = {1175-5334}, doi = {10.11646/zootaxa.4729.2.6}, author = {Agarwal, Ishan and Bauer, Aaron M and Pal, Saunak and Srikanthan, Achyuthan N and Khandekar, Akshay} } @article {83637, title = {Using virtual worlds to understand insect navigation for bio-inspired systems.}, journal = {Curr Opin Insect Sci}, year = {2020}, month = {2020 Sep 30}, abstract = {

Insects perform a wide array of intricate behaviors over large spatial and temporal scales in complex natural environments. A mechanistic understanding of insect cognition has direct implications on how brains integrate multimodal information and can inspire bio-based solutions for autonomous robots. Virtual Reality (VR) offers an opportunity assess insect neuroethology while presenting complex, yet controlled, stimuli. Here, we discuss the use of insects as inspiration for artificial systems, recent advances in different VR technologies, current knowledge gaps, and the potential for application of insect VR research to bio-inspired robots. Finally, we advocate the need to diversify our model organisms, behavioral paradigms and embrace the complexity of the natural world. This will help in uncovering the proximate and ultimate basis of brain and behavior and extract general principles for common challenging problems.

}, issn = {2214-5753}, doi = {10.1016/j.cois.2020.09.010}, author = {Kaushik, Pavan Kumar and Olsson, Shannon B} } @article {77387, title = {The Variations of Human miRNAs and Ising Like Base Pairing Models}, journal = {MATCH-COMMUNICATIONS IN MATHEMATICAL AND IN COMPUTER CHEMISTRY}, volume = {83}, year = {2020}, month = {2020}, pages = {357-372}, abstract = {

miRNAs are small about 22-base pair long, RNA molecules are of significant biological importance. Like other longer RNA molecules, messages in miRNAs are words in an alphabet consists of only four nucleotide bases. However, just like words in any language, not all combinations of these alphabets are not meaningful. In fact, we find that the distributions of nucleotides bases in human miRNAs show significant deviation from randomness. First, a miRNA sequence containing four bases are mapped into a binary string with three kinds of classifications according to their chemical properties. Our analyses based on some statistical measurement clearly demonstrate that the purines-pyrimidines class of nucleotide bases resembles all the human miRNAs. Then, we propose a simple nearest neighbor model (Ising model) to understand the statistical variations in human miRNAs. One the way, we also discuss the limitations of a mean-field model.

}, author = {Banerjee, JP and Das, JK and Choudhury, PP and Mukherjee, S and Hassan, SS and Basu, P} } @article {77434, title = {The Viral SUMO-Targeted Ubiquitin Ligase ICP0 is Phosphorylated and Activated by Host Kinase Chk2.}, journal = {J Mol Biol}, volume = {432}, year = {2020}, month = {2020 Mar 27}, pages = {1952-1977}, abstract = {

When the herpes simplex virus (HSV) genome enters the nucleus for replication and transcription, phase-segregated nuclear protein bodies called Promyelocytic leukemia protein nuclear bodies (PML NBs) colocalize with the genome and repress it. HSV encodes a small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase (STUbL) infected cell polypeptide 0 (ICP0) that degrades PML NBs to alleviate the repression. The molecular details of the mechanism used by ICP0 to target PML NBs are unclear. Here, we identify a bona fide SUMO-interacting motif in ICP0 (SIM-like sequence [SLS] 4) that is essential and sufficient to target SUMOylated proteins in PML NBs such as the PML and Sp100. We shown that phosphorylation of SLS4 creates new salt bridges between SUMO and SLS4, increases the SUMO/SLS4 affinity, and switches ICP0 into a potent STUbL. HSV activates the Ataxia-telangiectasia-mutated kinase-Checkpoint kinase 2 (ATM-Chk2) pathway to regulate the cell cycle of the host. We report that the activated Chk2 also phosphorylates ICP0 at SLS4 and enhances its STUbL activity. Our results uncover that a viral STUbL counters antiviral response by exploiting an unprecedented cross-talk of three post-translational modifications: ubiquitination, SUMOylation, and phosphorylation.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2020.01.021}, author = {Hembram, Dambarudhar Shiba Sankar and Negi, Hitendra and Biswas, Poulomi and Tripathi, Vasvi and Bhushan, Lokesh and Shet, Divya and Kumar, Vikas and Das, Ranabir} } @article {78159, title = {Visualizing mutagenic repair: novel insights into bacterial translesion synthesis.}, journal = {FEMS Microbiol Rev}, year = {2020}, month = {2020 Jun 18}, abstract = {

DNA repair is essential for cell survival. In all domains of life, error-prone and error-free repair pathways ensure maintenance of genome integrity under stress. Although mutagenic, low fidelity repair mechanisms help avoid potential lethality associated with unrepaired damage, thus making them important for genome maintenance, and in some cases, the preferred mode of repair. However, cells carefully regulate pathway choice to restrict activity of these pathways to only certain conditions. One such repair mechanism is Translesion Synthesis (TLS), where a low fidelity DNA polymerase is employed to synthesize across a lesion. In bacteria, TLS is a potent source of stress-induced mutagenesis, with potential implications in cellular adaptation as well as antibiotic resistance. Extensive genetic and biochemical studies, predominantly in Escherichia coli, have established a central role for TLS in bypassing bulky DNA lesions associated with ongoing replication, either at or behind the replication fork. More recently, imaging-based approaches have been applied to understand the molecular mechanisms of TLS and how its function is regulated. Together, these studies have highlighted replication-independent roles for TLS as well. In this review, we discuss the current status of research on bacterial TLS, with emphasis on recent insights gained mostly through microscopy at the single-cell and single-molecule level.

}, issn = {1574-6976}, doi = {10.1093/femsre/fuaa023}, author = {Joseph, Asha Mary and Badrinarayanan, Anjana} } @article {78163, title = {Wave exposure reduces herbivory in post-disturbed reefs by filtering species composition, abundance and behaviour~of key fish herbivores.}, journal = {Sci Rep}, volume = {10}, year = {2020}, month = {2020 Jun 19}, pages = {9854}, abstract = {

Harsh environmental conditions limit how species use the landscape, strongly influencing the way assemblages are distributed. In the wake of repeated coral bleaching mortalities in Lakshadweep, we examined how wave exposure influences herbivory \ in exposed and sheltered reefs. We used a combination of i. field observations of fish herbivore composition, abundance and activity across 6 exposed and 6 sheltered reefs; ii. experimental manipulations in a subset of these reefs (herbivore exclosures); and iii. opportunistic observations of fish recruitment, to determine how exposure influences herbivore biomass and herbivory. Species richness, biomass, abundance, total bite rates and species-specific per capita bite rates were lower in exposed compared to sheltered reefs, linked to strong environmental filtering of species composition, abundance and behaviour. For some critical species, this environmental filtering begins with differential recruitment and post-recruitment processes between exposures. Bite rates at sheltered sites were dominated by just a few species, most being laterally compressed surgeonfish that may find it difficult accessing or surviving in wave-battered shallow reefs. Exclosure experiments confirmed \ that exposed reefs \ were less controlled by herbivores than sheltered reefs. In post-disturbed reefs like Lakshadweep, environmental gradients appear to be key mediators of critical functions like herbivory by determining species composition, abundance and behaviour.

}, issn = {2045-2322}, doi = {10.1038/s41598-020-66475-y}, author = {Karkarey, Rucha and Rathod, Pooja and Arthur, Rohan and Yadav, Shreya and Theo, Anne and Alcoverro, Teresa} } @article {84075, title = {Whole-Genome Sequencing of sp. Strain RSMS, a Highly Efficient Tributyl Phosphate-Degrading Bacterium.}, journal = {Microbiol Resour Announc}, volume = {9}, year = {2020}, month = {2020 Oct 15}, abstract = {

sp. strain RSMS was described earlier as an efficient degrader of tributyl phosphate, an organic pollutant. This report describes the generation and annotation of the genome sequence of sp. strain RSMS, which will facilitate future studies to identify genetic elements responsible for the degradation of tributyl phosphate.

}, issn = {2576-098X}, doi = {10.1128/MRA.00600-20}, author = {Rangu, Shyam Sunder and Beck, Ashish and Sharda, Mohak and Mukhopadhyaya, Rita and Seshasayee, Aswin Sai Narain and Rath, Devashish} } @article {78265, title = {α-Synuclein aggregation nucleates through liquid-liquid phase separation.}, journal = {Nat Chem}, year = {2020}, month = {2020 Jun 08}, abstract = {

α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson{\textquoteright}s disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson{\textquoteright}s disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson{\textquoteright}s disease pathogenesis.

}, issn = {1755-4349}, doi = {10.1038/s41557-020-0465-9}, author = {Ray, Soumik and Singh, Nitu and Kumar, Rakesh and Patel, Komal and Pandey, Satyaprakash and Datta, Debalina and Mahato, Jaladhar and Panigrahi, Rajlaxmi and Navalkar, Ambuja and Mehra, Surabhi and Gadhe, Laxmikant and Chatterjee, Debdeep and Sawner, Ajay Singh and Maiti, Siddhartha and Bhatia, Sandhya and Gerez, Juan Atilio and Chowdhury, Arindam and Kumar, Ashutosh and Padinhateeri, Ranjith and Riek, Roland and Krishnamoorthy, G and Maji, Samir K} } @article {49144, title = {5-HT deletion protects against Clozapine-induced hyperglycemia.}, journal = {J Pharmacol Sci}, volume = {139}, year = {2019}, month = {2018 Dec 18}, pages = {133-135}, abstract = {

Clozapine is an antipsychotic known for its superior efficacy in treating drug-resistant Schizophrenia. However, Clozapine induces various side effects such as hyperglycemia, agranulocytosis, weight gain etc. The mechanisms of these Clozapine-induced side effects have remained largely elusive though an important role is ascribed to 5-HT (Serotonin receptor subtype-2A). In this pilot study, we report for the first time that the 5-HT {\textquoteright}global{\textquoteright} knockout mice (Htr2a) are resistant to the Clozapine-induced hyperglycemia. Importantly though, the Htr2a mice exhibit near normal basal glucose metabolism in the glucose tolerance tests. Collectively, the Htr2a mice provide an important tool to study the Clozapine-induced hyperglycemia.

}, issn = {1347-8648}, doi = {10.1016/j.jphs.2018.11.015}, author = {Joshi, Radhika Sudhir and Singh, Shishu Pal and Panicker, Mitradas M} } @article {74438, title = {Active morphogenesis of epithelial monolayers.}, journal = {Phys Rev E}, volume = {100}, year = {2019}, month = {2019 Aug}, pages = {022413}, abstract = {

During typical early-stage embryo development, single-cell-thick tissues of tightly bound epithelial cells autonomously generate profound changes in their shape, forming the basis of organism anatomy. We report on a (covariant) active-hydrodynamic theory of such monolayer morphogenesis that is closed under its shape-changing dynamics-i.e., the degrees of freedom that encode monolayer geometry appear properly as broken-symmetry variables. In our theory, the salient physics of tissue-scale deformations emerges from a balance between the displacement and/or shear of a low-Reynolds-number embedding fluid (the "yolk") and cell-autonomous stresses, themselves a result of combining apical contractile stresses with an elastic-like mechanical response under the constraint of constant cell volume. The leading-order hydrodynamic instabilities include both passive constrained-buckling and active deformation, which can be further categorized by cell shape changes that are either "squamous to columnar" or "regular-prism to truncated-pyramid." The deformations resulting from the latter qualitatively reproduce in vivo observations of the onset of both mesoderm and posterior midgut invaginations, which take place during gastrulation in the model organism Drosophila melanogaster.

}, keywords = {Epithelium, Hydrodynamics, Models, Biological, Morphogenesis, Thermodynamics}, issn = {2470-0053}, doi = {10.1103/PhysRevE.100.022413}, author = {Morris, Richard G and Rao, Madan} } @article {62775, title = {Adult Drosophila muscle morphometry through microCT reveals dynamics during ageing.}, journal = {Open Biol}, volume = {9}, year = {2019}, month = {2019 Jun 28}, pages = {190087}, abstract = {

Indirect flight muscles (IFMs) in adult Drosophila provide the key power stroke for wing beating. They also serve as a valuable model for studying muscle development. An age-dependent decline in Drosophila free flight has been documented, but its relation to gross muscle structure has not yet been explored satisfactorily. Such analyses are impeded by conventional histological preparations and imaging techniques that limit exact morphometry of flight muscles. In this study, we employ microCT scanning on a tissue preparation that retains muscle morphology under homeostatic conditions. Focusing on a subset of IFMs called the dorsal longitudinal muscles (DLMs), we find that DLM volumes increase with age, partially due to the increased separation between myofibrillar fascicles, in a sex-dependent manner. We have uncovered and quantified asymmetry in the size of these muscles on either side of the longitudinal midline. Measurements of this resolution and scale make substantive studies that test the connection between form and function possible. We also demonstrate the application of this method to other insect species making it a valuable tool for histological analysis of insect biodiversity.

}, issn = {2046-2441}, doi = {10.1098/rsob.190087}, author = {Chaturvedi, Dhananjay and Prabhakar, Sunil and Aggarwal, Aman and Atreya, Krishan B and VijayRaghavan, K} } @article {62766, title = {Adult Neurogenesis and the Promise of Adult Neural Stem Cells.}, journal = {J Exp Neurosci}, volume = {13}, year = {2019}, month = {2019}, pages = {1179069519856876}, abstract = {

The adult brain, even though largely postmitotic, is now known to have dividing cells that can make both glia and neurons. Of these, the precursor cells that have the potential to make new neurons in the adult brain have attracted great attention from researchers, anticipating their therapeutic potential for neurodegenerative conditions. In this review, I will focus on adult neurogenesis, from the perspective of the overall neurogenic potential in the adult brain, current understanding of the {\textquoteright}adult neural stem cell{\textquoteright}, and the importance of as a decisive factor for neurogenesis under homeostasis and pathologic conditions.

}, issn = {1179-0695}, doi = {10.1177/1179069519856876}, author = {Ghosh, Hiyaa S} } @article {67817, title = {Altered dendritic spine function and integration in a mouse model of fragile X syndrome.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Oct 23}, pages = {4813}, abstract = {

Cellular and circuit hyperexcitability are core features of fragile X syndrome and related autism spectrum disorder models. However, the cellular and synaptic bases of this hyperexcitability have proved elusive. We report in a mouse model of fragile X syndrome, glutamate uncaging onto individual dendritic spines yields stronger single-spine excitation than wild-type, with more silent spines. Furthermore, fewer spines are required to trigger an action potential with near-simultaneous uncaging at multiple spines. This is, in part, from increased dendritic gain due to increased intrinsic excitability, resulting from reduced hyperpolarization-activated currents, and increased NMDA receptor signaling. Using super-resolution microscopy we detect no change in dendritic spine morphology, indicating no structure-function relationship at this age. However, ultrastructural analysis shows a 3-fold increase in multiply-innervated spines, accounting for the increased single-spine glutamate currents. Thus, loss of FMRP causes abnormal synaptogenesis, leading to large numbers of poly-synaptic spines despite normal spine morphology, thus explaining the synaptic perturbations underlying circuit hyperexcitability.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-11891-6}, author = {Booker, Sam A and Domanski, Aleksander P F and Dando, Owen R and Jackson, Adam D and Isaac, John T R and Hardingham, Giles E and Wyllie, David J A and Kind, Peter C} } @article {53185, title = {Amniotic membrane as novel scaffold for human iPSC-derived cardiomyogenesis.}, journal = {In Vitro Cell Dev Biol Anim}, year = {2019}, month = {2019 Feb 24}, abstract = {

Recent approaches of using decellularized organ matrices for cardiac tissue engineering prompted us to culture human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) on the human amniotic membrane (hAM). Since hAM has been used lately to patch diseased hearts in patients and has shown anti-inflammatory and anti-fibrotic benefits, it qualifies as a cardiac compatible and clinically relevant heart tissue scaffold. The aim of this study was to test the ability of the hAM to support attachment, differentiation, and maturation of hiPSC-derived CMs in vitro. hAMs were prepared from term placenta. An in-house generated hiPSC line was used for CM derivation. hiPSC-derived cardiac progenitors were cultured on the surface of cryopreserved hAMs and in the presence of cytokines promoting cardiac differentiation. CMs grown on hAM and popular basement membrane matrix (BMM) Matrigel{\texttrademark} were compared for the following aspects of cardiac development: the morphology of cardiomyocytes with respect to shape and cellular alignments, levels of cardiac-related gene transcript expression, functionality in terms of spontaneous calcium fluxes and mitochondrial densities and distributions. hAM is biocompatible with hiPSC-derived CMs. hAM increased cardiac transcription regulator and myofibril protein transcript expression, accelerated intracellular calcium transients, and enhanced cellular mitochondrial complexity of its cardiomyocytes in comparison to cardiomyocytes differentiated on Matrigel{\texttrademark}. Our data suggests that hAM supports differentiation and improves cardiomyogenesis in comparison to Matrigel{\texttrademark}. hAMs are natural, easily and largely available. The method of preparing hAM cardiac sheets described here is simple with potential for clinical transplantation. Graphical abstract A An outline of the differentiation protocol with stage-specific growth factors and culture media used. B Cell fates from pluripotent stem cells to cardiomyocytes during differentiation on the amniotic membrane. C-FPhotomicrographs of cells at various stages of differentiation. Scale bars represent 100\ μm.

}, issn = {1543-706X}, doi = {10.1007/s11626-019-00321-y}, author = {Parveen, Shagufta and Singh, Shishu Pal and Panicker, M M and Gupta, Pawan Kumar} } @article {59719, title = {Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics.}, journal = {Dev Cell}, volume = {49}, year = {2019}, month = {2019 Jun 17}, pages = {894-906.e12}, abstract = {

RhoA stimulates cell contractility by recruiting downstream effectors to the cortical plasma membrane. We now show that direct binding by anillin is required for effective signaling: this antagonizes the otherwise labile membrane association of GTP-RhoA to promote effector recruitment. However, since its binding to RhoA blocks access by other effectors, we demonstrate that anillin must also concentrate membrane phosphoinositide-4,5-P (PIP) to promote signaling. We propose and test a sequential pathway where GTP-RhoA first binds to anillin and then is retained at the membrane by PIP after it disengages from anillin. Importantly, re-binding of membrane GTP-RhoA to anillin, regulated by the cortical density of anillin, creates cycles through this pathway. These cycles repeatedly reset the dissociation kinetics of GTP-RhoA, substantially increasing its dwell time to\ recruit effectors. Thus, anillin regulates RhoA signaling by a paradigm of kinetic scaffolding that may apply to other signals whose efficacy depends on their cortical dwell times.

}, issn = {1878-1551}, doi = {10.1016/j.devcel.2019.04.031}, author = {Budnar, Srikanth and Husain, Kabir B and Gomez, Guillermo A and Naghibosadat, Maedeh and Varma, Amrita and Verma, Suzie and Hamilton, Nicholas A and Morris, Richard G and Yap, Alpha S} } @article {62920, title = {Ants, fire, and bark traits affect how African savanna trees recover following damage}, journal = {BIOTROPICA}, year = {2019}, month = {07/2019}, abstract = {

Bark damage resulting from elephant feeding is common in African savanna trees with subsequent interactions with fire, insects, and other pathogens often resulting in tree mortality. Yet, surprisingly little is known about how savanna trees respond to bark damage. We addressed this by investigating how the inner bark of marula (Sclerocarya birrea), a widespread tree species favoured by elephants, recovers after bark damage. We used a long-term fire experiment in the Kruger National Park to measure bark recovery with and without fire. At 24\ months post-damage, mean wound closure was 98, 92, and 72\%, respectively, in annual and biennial burns and fire-exclusion treatments. Fire exclusion resulted in higher rates of ant colonization of bark wounds, and such ant colonization resulted in significantly lower bark recovery. We also investigated how ten common savanna tree species respond to bark damage and tested for relationships between bark damage, bark recovery, and bark traits while accounting for phylogeny. We found phylogenetic signal in bark dry matter content, bark N and bark P, but not in bark thickness. Bark recovery and damage was highest in species which had thick moist inner bark and low wood densities (Anacardiaceae), intermediate in species which had moderate inner bark thickness and wood densities (Fabaceae) and lowest in species which had thin inner bark and high wood densities (Combretaceae). Elephants prefer species with thick, moist inner bark, traits that also appear to result in faster recovery rates.

}, doi = {10.1111/btp.12683}, author = {Wigley, BJ and Coetsee, C and Kruger, LM and Ratnam, J and Sankaran, M} } @article {51229, title = {Apis florea workers show a prolonged period of nursing behavior}, journal = {Apidologie}, year = {2019}, month = {01/2019}, abstract = {

Studies on behavioral maturation and division of labor in open-nesting honey bee species are scarce as the bee curtain inhibits direct examination of intranidal behaviors. We observed and studied nursing behavior in Apis florea by attaching a foreign comb with open brood to a host colony. Several of the workers that explored the attached comb visited the cells with brood more often and spent more time in cells compared to empty cells. Workers seen inspecting and feeding the brood had well-developed hypopharyngeal glands compared to foragers of their own colony indicating that they are nurses performing nursing behavior. Further, introducing marked 1-day-old workers into the host colony and repeatedly attaching combs with open brood allowed us to estimate the age range of nursing behavior. In our experiments, A. florea workers started to perform significant nursing behavior 8 days after eclosion and continued to show nursing behavior until the age of 28 days, the end of our observation period. Thus, nursing behavior in A. florea appears to be substantially extended relative to A. mellifera .

}, doi = {10.1007/s13592-018-0618-7}, author = {Bhagavan, H and Brockmann, Axel} } @article {55792, title = {Asrij/OCIAD1 suppresses CSN5-mediated p53 degradation and maintains mouse hematopoietic stem cell quiescence.}, journal = {Blood}, year = {2019}, month = {2019 Apr 05}, abstract = {

Inactivation of the tumor suppressor p53 is essential for unrestrained growth of cancers. However, only 11\% of hematological malignancies have mutant p53. Mechanisms that cause wild type p53 dysfunction and promote leukemia are inadequately deciphered. The stem cell protein Asrij/OCIAD1 is misexpressed in several human hematological malignancies and implicated in the p53 pathway and DNA damage response. However, Asrij function in vertebrate hematopoiesis remains unknown. We generated the first asrij null (knockout, KO) mice and show that they are viable and fertile with no gross abnormalities. However, by six months, they exhibit increased peripheral blood cell counts, splenomegaly and an expansion of bone marrow hematopoietic stem cells (HSCs) with higher myeloid output. HSCs lacking Asrij are less quiescent and more proliferative with higher repopulation potential as observed from serial transplantation studies. However, stressing KO mice with sub-lethal gamma irradiation or multiple injections of 5-fluorouracil results in reduced survival and rapid depletion of hematopoietic stem/progenitor cells (HSPCs) by driving them into proliferative exhaustion. Molecular and biochemical analyses revealed increased polyubiquitinated protein levels, Akt/STAT5 activation and CSN5 (COP9 signalosome subunit 5)-mediated p53 ubiquitination and degradation in KO HSPCs. Further, we show that Asrij sequesters CSN5 via its conserved OCIA domain, thereby preventing p53 degradation. In agreement, Nutlin-3 treatment of KO mice restored p53 levels and reduced high HSPC frequencies. Thus, we provide a new mouse model resembling myeloproliferative disease and identify a post-translational regulator of wild type p53 essential for maintaining HSC quiescence that could be a potential target for pharmacological intervention.

}, issn = {1528-0020}, doi = {10.1182/blood.2019000530}, author = {Sinha, Saloni and Dwivedi, Tirath Raj and Yengkhom, Roja and Bheemsetty, Venkata Anudeep and Abe, Takaya and Kiyonari, Hiroshi and VijayRaghavan, K and Inamdar, Maneesha S} } @article {66845, title = {Attitude, perception and awareness of stakeholders towards the protected marine species in the Andaman Islands}, journal = {OCEAN \& COASTAL MANAGEMENT}, volume = {179}, year = {2019}, month = {09/2019}, chapter = {104830}, abstract = {

Examining stakeholder{\textquoteright}s knowledge, perception and attitudes are necessary for effective implementation of laws that are designed to protect and conserve marine biodiversity. In order to understand knowledge, awareness and perception about the law and the species that are protected under the Indian Wildlife (Protection) Act, 1972, I interviewed (N = 159) stakeholders (77 fishermen, 39 authorities and 41 middlemen/traders) in the Andaman Islands, India. Within respondents, mean awareness about different protected marine species was (80\%) amongst authorities, followed by (63\%) amongst traders/middlemen and (59\%) amongst fishermen. The awareness about a few charismatic groups i.e., mammals, reptiles and cnidarians high; whereas awareness about elasmobranchs, fish, sea cucumbers and molluscs low amongst the respondent groups. Amongst several species traded in the islands, the sea cucumber, the trochus and the turbo are in high demand, and there is demand from middlemen and fishers to delist these species. Generalised model revealed that the years of fishing experience, occupation, annual income and age of respondents are important factors in determining awareness of locals towards protected species. Solutions suggested by stakeholders are strict enforcement of the law, education and awareness of protected species, a special task force for dealing with the Indian Wildlife Protection Act, need to curb poaching from foreigners etc. All fishers sell their catch to middlemen/traders who in turn send their catch to mainland India (Tamil Nadu and Kolkata). The knowledge about which government department is responsible for implementation and monitoring of the law is limited amongst all stakeholder groups. The study demonstrates that stakeholder{\textquoteright}s knowledge, perception and attitude can offer valuable insights towards strengthening the law that protects marine species. Similar studies should be carried out across different coastal states to understand the level of awareness of stakeholders towards protected marine species. Creating awareness, inclusiveness of local stakeholders in decision making, empowering authorities in monitoring can help in strengthening the existing law framework for protected marine species.

}, doi = {10.1016/j.ocecoaman.2019.104830}, author = {Patankar, VJ} } @article {70226, title = {Binding-induced folding under unfolding conditions: Switching between induced fit and conformational selection mechanisms.}, journal = {J Biol Chem}, volume = {294}, year = {2019}, month = {2019 Nov 08}, pages = {16942-16952}, abstract = {

The chemistry of protein-ligand binding is the basis of virtually every biological process. Ligand binding can be essential for a protein to function in the cell by stabilizing or altering the conformation of a protein, particularly for partially or completely unstructured proteins. However, the mechanisms by which ligand binding impacts disordered proteins or influences the role of disorder in protein folding is not clear. To gain insight into this question, the mechanism of folding induced by the binding of a Pro-rich peptide ligand to the SH3 domain of phosphatidylinositol 3-kinase unfolded in the presence of urea has been studied using kinetic methods. Under strongly denaturing conditions, folding was found to follow a conformational selection (CS) mechanism. However, under mildly denaturing conditions, a ligand concentration-dependent switch in the mechanism was observed. The folding mechanism switched from being predominantly a CS mechanism at low ligand concentrations to being predominantly an induced fit (IF) mechanism at high ligand concentrations. The switch in the mechanism manifests itself as an increase in the reaction flux along the IF pathway at high ligand concentrations. The results indicate that, in the case of intrinsically disordered proteins too, the folding mechanism is determined by the concentration of the ligand that induces structure formation.

}, issn = {1083-351X}, doi = {10.1074/jbc.RA119.009742}, author = {Sen, Sreemantee and Udgaonkar, Jayant B} } @article {72075, title = {Breakdown of effective temperature, power law interactions, and self-propulsion in a momentum-conserving active fluid.}, journal = {Phys Rev E}, volume = {100}, year = {2019}, month = {2019 Dec}, pages = {062602}, abstract = {

The simplest extensions of single-particle dynamics in a momentum-conserving active fluid-an active suspension of two colloidal particles or a single particle confined by a wall-exhibit strong departures from Boltzmann behavior, resulting in either a breakdown of an effective temperature description or a steady state with nonzero-entropy production rate. This is a consequence of hydrodynamic interactions that introduce multiplicative noise in the stochastic description of particle positions. This results in fluctuation-induced interactions that depend on distance as a power law. We find that the dynamics of activated colloids in a passive fluid, with stochastic forcing localized on the particle, is different from that of passive colloids in an active fluctuating fluid.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.100.062602}, author = {Vishen, Amit Singh and Prost, Jacques and Rao, Madan} } @article {55794, title = {Building behaviors, one layer at a time.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Apr 04}, abstract = {

New interneurons are added in the hindbrain to support more complex movements as young zebrafish get older.

}, issn = {2050-084X}, doi = {10.7554/eLife.46375}, author = {Wyart, Claire and Thirumalai, Vatsala} } @article {57787, title = {The Ca2+ Channel CNGC19 Regulates Arabidopsis defense against Spodoptera Herbivory.}, journal = {Plant Cell}, year = {2019}, month = {2019 May 10}, abstract = {

Cellular calcium elevation is an important signal used by plants for recognition and signaling of environmental stress. Perception of the generalist insect, Spodoptera litura, by Arabidopsis thaliana activates cytosolic Ca2+ elevation, which triggers downstream defense. However, not all the Ca2+ channels generating the signal have been identified, nor are their modes of action known. We report on a rapidly activated, leaf vasculature- and plasma membrane-localized, CYCLIC NUCLEOTIDE GATED CHANNEL19 (CNGC19), which activates herbivory-induced Ca2+ flux and plant defense. Loss of CNGC19 function results in decreased herbivory defense. The cngc19 mutant shows aberrant and attenuated intra-vascular Ca2+ fluxes. CNGC19 is a Ca2+ permeable channel, as hyperpolarization of CNGC19-expressing Xenopus oocytes in the presence of both cAMP and Ca2+ results in Ca2+ influx. Breakdown of Ca2+-based defence in cngc19 mutants leads to a decrease in herbivory-induced JA-Ile biosynthesis and expression of JA responsive genes. cngc19 mutants are deficient in aliphatic glucosinolate accumulation and hyperaccumulate its precursor, methionine. CNGC19 modulates aliphatic glucosinolate biosynthesis in tandem with BRANCHED-CHAIN AMINO ACID TRANSAMINASE4 (BCAT4), which is involved in the chain elongation pathway of Met-derived glucosinolates. Furthermore, CNGC19 interacts with herbivory-induced CALMODULIN2 (CaM2) in planta. Together, our work reveals a key mechanistic role for the Ca2+ channel CNGC19 in the recognition of herbivory and the activation of defense signaling.

}, issn = {1532-298X}, doi = {10.1105/tpc.19.00057}, author = {Meena, Mukesh Kumar and Prajapati, Ramgopal and Krishna, Deepthi and Divakaran, Keerthi and Pandey, Yogesh and Reichelt, Michael and Mathew, M K and Boland, Wilhelm and Mith{\"o}fer, Axel and Vadassery, Jyothilakshmi} } @article {62756, title = {Casein kinase-2 mediated phosphorylation increases the SUMO-dependent activity of the cytomegalovirus transactivator IE2.}, journal = {J Biol Chem}, year = {2019}, month = {2019 Aug 01}, abstract = {

Many viral factors manipulate the host post-translational modification (PTM) machinery for efficient viral replication. In particular, phosphorylation and SUMOylation can distinctly regulate the activity of the human cytomegalovirus (HCMV) transactivator immediate early 2 (IE2). However, the molecular mechanism of this process is unknown. Using various structural, biochemical, and cell-based approaches, here we uncovered that IE2 exploits a cross-talk between phosphorylation and SUMOylation. A scan for SUMO-interacting motifs (SIMs) revealed two SIMs in IE2, and a real-time SUMOylation assay indicated that the N-terminal SIM (IE2-SIM1) enhances IE2 SUMOylation up to 4-fold. Kinetic analysis and structural studies disclosed that IE2 is a SUMO cis-E3 ligase. We also found that two putative casein kinase 2 (CK2) sites adjacent to IE2-SIM1 are phosphorylated in-vitro and in cells. The phosphorylation drastically increased IE2-SUMO affinity, IE2 SUMOylation, and cis-E3 activity of IE2. Additional salt bridges between the phosphoserines and SUMO accounted for the increased IE2-SUMO affinity. Phosphorylation also enhances the SUMO-dependent transactivation activity and auto-repression activity of IE2. Together, our findings highlight a novel mechanism whereby SUMOylation and phosphorylation of the viral cis-E3 ligase and transactivator protein IE2 works in tandem to enable transcriptional regulation of viral gene.

}, issn = {1083-351X}, doi = {10.1074/jbc.RA119.009601}, author = {Tripathi, Vasvi and Chatterjee, Kiran Sankar and Das, Ranabir} } @article {67818, title = {Cellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Oct 23}, pages = {4814}, abstract = {

Sensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). How developmental changes in neuronal function culminate in network dysfunction that underlies sensory hypersensitivities is unknown. By systematically studying cellular and synaptic properties of layer 4 neurons combined with cellular and network simulations, we explored how the array of phenotypes in Fmr1-knockout (KO) mice produce circuit pathology during development. We show that many of the cellular and synaptic pathologies in Fmr1-KO mice are antagonistic, mitigating circuit dysfunction, and hence may be compensatory to the primary pathology. Overall, the layer 4 network in the Fmr1-KO exhibits significant alterations in spike output in response to thalamocortical input and distorted sensory encoding. This developmental loss of layer 4 sensory encoding precision would contribute to subsequent developmental alterations in layer 4-to-layer 2/3 connectivity and plasticity observed in Fmr1-KO mice, and circuit dysfunction underlying sensory hypersensitivity.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-12736-y}, author = {Domanski, Aleksander P F and Booker, Sam A and Wyllie, David J A and Isaac, John T R and Kind, Peter C} } @article {50999, title = {On chaotic dynamics in transcription factors and the associated effects in differential gene regulation.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 01 08}, pages = {71}, abstract = {

The control of proteins by a transcription factor with periodically varying concentration exhibits intriguing dynamical behaviour. Even though it is accepted that transcription factors vary their dynamics in response to different situations, insight into how this affects downstream genes is lacking. Here, we investigate how oscillations and chaotic dynamics in the transcription factor NF-κB can affect downstream protein production. We describe how it is possible to control the effective dynamics of the transcription factor by stimulating it with an oscillating ligand. We find that chaotic dynamics modulates gene expression and up-regulates certain families of low-affinity genes, even in the presence of extrinsic and intrinsic noise. Furthermore, this leads to an increase in the production of protein complexes and the efficiency of their assembly. Finally, we show how chaotic dynamics creates a heterogeneous population of cell states, and describe how this can be beneficial in multi-toxic environments.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-07932-1}, author = {Heltberg, Mathias L and Krishna, Sandeep and Jensen, Mogens H} } @article {54455, title = {ChIPulate: A comprehensive ChIP-seq simulation pipeline.}, journal = {PLoS Comput Biol}, volume = {15}, year = {2019}, month = {2019 Mar 21}, pages = {e1006921}, abstract = {

ChIP-seq (Chromatin Immunoprecipitation followed by sequencing) is a high-throughput technique to identify genomic regions that are bound in vivo by a particular protein, e.g., a transcription factor (TF). Biological factors, such as chromatin state, indirect and cooperative binding, as well as experimental factors, such as antibody quality, cross-linking, and PCR biases, are known to affect the outcome of ChIP-seq experiments. However, the relative impact of these factors on inferences made from ChIP-seq data is not entirely clear. Here, via a detailed ChIP-seq simulation pipeline, ChIPulate, we assess the impact of various biological and experimental sources of variation on several outcomes of a ChIP-seq experiment, viz., the recoverability of the TF binding motif, accuracy of TF-DNA binding detection, the sensitivity of inferred TF-DNA binding strength, and number of replicates needed to confidently infer binding strength. We find that the TF motif can be recovered despite poor and non-uniform extraction and PCR amplification efficiencies. The recovery of the motif is, however, affected to a larger extent by the fraction of sites that are either cooperatively or indirectly bound. Importantly, our simulations reveal that the number of ChIP-seq replicates needed to accurately measure in vivo occupancy at high-affinity sites is larger than the recommended community standards. Our results establish statistical limits on the accuracy of inferences of protein-DNA binding from ChIP-seq and suggest that increasing the mean extraction efficiency, rather than amplification efficiency, would better improve sensitivity. The source code and instructions for running ChIPulate can be found at https://github.com/vishakad/chipulate.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1006921}, author = {Datta, Vishaka and Hannenhalli, Sridhar and Siddharthan, Rahul} } @article {70229, title = {Close-up observations on the spawning behavior of a captive Japanese flying squid (Todarodes pacificus).}, journal = {Sci Rep}, volume = {9}, year = {2019}, month = {2019 Dec 24}, pages = {19739}, abstract = {

The spawning behavior of a Japanese flying squid (Todarodes pacificus) is described based on up-close observation of a captive female. The squid was first transferred from a 10-ton tank to a polystyrene plastic box containing 45 liters of seawater. About one hour later, the mantle-contraction rate increased rapidly, followed by a brief convulsion of the mantle and arms and a whitening of the body. The mantle contractions become shallow and rapid, and several seconds later, semitransparent jelly presumably from the nidamental glands emerged from the funnel and passed between the ventral pair of arms. Approximately 90 seconds after the egg mass first emerged, the female began ejecting oocytes through the funnel into the egg mass using rapid, powerful mantle contractions. Soon after the oocytes were ejected, translucent strands (presumably sperm) emanated from the buccal membrane. The female continued to eject oocytes for approximately two minutes, after which the mantle convulsed, and the mantle-contraction rate decreased slowly for about one minute until the contractions stopped. The squid died soon afterwards.

}, issn = {2045-2322}, doi = {10.1038/s41598-019-56071-0}, author = {Yamamoto, Jun and Adachi, Kohsuke and Bower, John R and Matsui, Hajime and Nakaya, Mitsuhiro and Ohtani, Ryusei and Puneeta, Pandey and Suzuki, Satoshi and Tokioka, Shun and Vijai, Dharmamony and Yanagimoto, Takashi and Yoo, Hae-Kyun} } @article {59705, title = {Coalescent theory of migration network motifs.}, journal = {Mol Biol Evol}, year = {2019}, month = {2019 Jun 04}, abstract = {

Natural populations display a variety of spatial arrangements, each potentially with a distinctive impact on genetic diversity and genetic differentiation among subpopulations. Although the spatial arrangement of populations can lead to intricate migration networks, theoretical developments have focused mainly on a small subset of such networks, emphasizing the island-migration and stepping-stone models. In this study, we investigate all small network motifs: the set of all possible migration networks among populations subdivided into at most four subpopulations. For each motif, we use coalescent theory to derive expectations for three quantities that describe genetic variation: nucleotide diversity, FST, and half-time to equilibrium diversity. We describe the impact of network properties on these quantities, finding that motifs with a high mean node degree have the largest nucleotide diversity and the longest time to equilibrium, whereas motifs with low density have the largest FST. In addition, we show that the motifs whose pattern of variation is most strongly influenced by loss of a connection or a subpopulation are those that can be split easily into disconnected components. We illustrate our results using two example datasets-sky island birds of genus Sholicola and Indian tigers-identifying disturbance scenarios that produce the greatest reduction in genetic diversity; for tigers, we also compare the benefits of two assisted gene flow scenarios. Our results have consequences for understanding the effect of geography on genetic diversity, and they can assist in designing strategies to alter population migration networks toward maximizing genetic variation in the context of conservation of endangered species.

}, issn = {1537-1719}, doi = {10.1093/molbev/msz136}, author = {Alcala, Nicolas and Goldberg, Amy and Ramakrishnan, Uma and Rosenberg, Noah A} } @article {66850, title = {Comment on "The global tree restoration potential".}, journal = {Science}, volume = {366}, year = {2019}, month = {2019 10 18}, abstract = {

Bastin {\textquoteright}s estimate (Reports, 5 July 2019, p. 76) that tree planting for climate change mitigation could sequester 205 gigatonnes of carbon is approximately five times too large. Their analysis inflated soil organic carbon gains, failed to safeguard against warming from trees at high latitudes and elevations, and considered afforestation of savannas, grasslands, and shrublands to be restoration.

}, keywords = {Carbon, Carbon Sequestration, Climate Change, Soil, Trees}, issn = {1095-9203}, doi = {10.1126/science.aay7976}, author = {Veldman, Joseph W and Aleman, Julie C and Alvarado, Swanni T and Anderson, T Michael and Archibald, Sally and Bond, William J and Boutton, Thomas W and Buchmann, Nina and Buisson, Elise and Canadell, Josep G and Dechoum, Michele de S{\'a} and Diaz-Toribio, Milton H and Durigan, Giselda and Ewel, John J and Fernandes, G Wilson and Fidelis, Alessandra and Fleischman, Forrest and Good, Stephen P and Griffith, Daniel M and Hermann, Julia-Maria and Hoffmann, William A and Le Stradic, Soizig and Lehmann, Caroline E R and Mahy, Gregory and Nerlekar, Ashish N and Nippert, Jesse B and Noss, Reed F and Osborne, Colin P and Overbeck, Gerhard E and Parr, Catherine L and Pausas, Juli G and Pennington, R Toby and Perring, Michael P and Putz, Francis E and Ratnam, Jayashree and Sankaran, Mahesh and Schmidt, Isabel B and Schmitt, Christine B and Silveira, Fernando A O and Staver, A Carla and Stevens, Nicola and Still, Christopher J and Str{\"o}mberg, Caroline A E and Temperton, Vicky M and Varner, J Morgan and Zaloumis, Nicholas P} } @article {56655, title = {Community-Level Responses to Iron Availability in Open Ocean Plankton Ecosystems}, journal = {GLOBAL BIOGEOCHEMICAL CYCLES}, volume = {33}, year = {2019}, month = {03/2019}, pages = {391-419}, abstract = {

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment.

Plain Language Summary Marine phytoplankton require iron for their growth and proliferation. According to John Martin{\textquoteright}s iron hypothesis, fertilizing the ocean with iron could dramatically increase photosynthetic activity, thus representing a biological means to counteract global warming. However, while there is a constantly growing knowledge of how iron is distributed in the ocean and about its role in cellular processes in marine photosynthetic groups such as diatoms and cyanobacteria, less is known about how iron availability shapes plankton communities and how they respond to it. In the present work, we exploited recently published Tara Oceans data sets to address these questions. We first defined specific subcommunities of co-occurring organisms that co-vary with iron availability in the oceans. We then identified specific patterns of adaptation and acclimation to iron in different groups of phytoplankton. Finally, we validated our global results at local scale, specifically in the Marquesas archipelago, where recurrent phytoplankton blooms arc believed to be a result of iron fertilization. By integrating global data with a localized response, we provide a framework for understanding the resilience of plankton ecosystems in a changing environment.

}, doi = {10.1029/2018GB006022}, author = {Caputi, L and Carradec, Q and Eveillard, D and Kirilovsky, A and Pelletier, E and Karlusich, J and Vieira, Fabio Rocha Jimenez and (Villar, E and Chaffron, S and Malviya, Shruti and Scalco, E and Acinas, Silvia G. and Alberti, A and Aury, Jean-Marc and Benoiston, Anne-Sophie and Bertrand, A and Biard, T and Bittner, L and Boccara, M and Brum, Jennifer R and Brunet, C and Busseni, G and Carratala, A and Claustre, H and Coelho, Luis Pedro and Colin, S and D{\textquoteright}Aniello, S and Da Silva, Corinne and Del Core, Marianna and Dore, H and Gasparini, S and Kokoszka, F and Jamet, Jean-Louis and Lejeusne, C and Lepoivre, C and Lescot, M and Lima-Mendez, Gipsi and Lombard, F and Lukes, J and Maillet, N and Madoui, Mohammed-Amin and Martinez, E and Mazzocchi, Maria Grazia and Neou, Mario B and Paz-Yepes, Javier and Poulain, Julie and Ramondenc, S and Romagnan, Jean-Baptiste and Roux, S and Manta, DS and Sanges, R and Speich, S and Sprovieri, M and Sunagawa, S and Taillandier, V and Tanaka, A and Tirichine, L and Trottier, C and Uitz, J and Veluchamy, A and Vesela, J and Vincent, F and Yau, S and Kandels-Lewis, Stefanie and Searson, S and Dimier, C and Picheral, M and Bork, P and Boss, E and De Vargas, C and Follows, M and Grimsley, N and Guidi, L and Hingamp, P and Karsenti, E and Sordino, P and Stemmann, L and Sullivan, MB and Tagliabue, A and Zingone, A and Garczarek, L and d{\textquoteright}Ortenzio, F and Testor, P and Not, F and d{\textquoteright}Alcala, MR and Wincker, P and Bowler, C and Iudicone, D and Gorsky, G and Jaillon, O and Karp-Boss, Lee and Krzic, U and Ogata, H and Pesant, S and Raes, J and Reynaud, EG and Sardet, C and Sieracki, M and Velayoudon, D and Weissenbach, J} } @article {43846, title = {Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum.}, journal = {Wellcome Open Res}, volume = {3}, year = {2019}, month = {01/2019}, pages = {44}, abstract = {

Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever. We also identified a small number of JEV sequences in the serum of two adults with febrile illness, including one with severe dengue. Phylogenetic analysis revealed that the dengue sequence belonged to genotype III. It has an estimated divergence time of 13.86 years from the most highly related Indian strains. In total, 11 amino acid substitutions were predicted for this strain in the antigenic envelope protein, when compared to the parent strain used for development of the first commercial dengue vaccine.\  We demonstrate that both genome assembly and detection of a low number of viral sequences are possible through the unbiased sequencing of clinical material. These methods may help ascertain causal agents for febrile illnesses with no known cause.

}, issn = {2398-502X}, doi = {10.12688/wellcomeopenres.14438.1}, author = {Dias, Mary and Pattabiraman, Chitra and Siddappa, Shilpa and Gowda, Malali and Shet, Anita and Smith, Derek and Muehlemann, Barbara and Tamma, Krishnapriya and Solomon, Tom and Jones, Terry and Krishna, Sudhir} } @article {62769, title = {A composition-dependent molecular clutch between T cell signaling condensates and actin.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Jul 03}, abstract = {

During T cell activation, biomolecular condensates form at the immunological synapse (IS) through multivalency-driven phase separation of LAT, Grb2, Sos1, SLP-76, Nck, and WASP. These condensates move radially at the IS, traversing successive radially-oriented and concentric actin networks. To understand this movement, we biochemically reconstituted LAT condensates with actomyosin filaments. We found that basic regions of Nck and N-WASP/WASP promote association and co-movement of LAT condensates with actin, indicating conversion of weak individual affinities to high collective affinity upon phase separation. Condensates lacking these components were propelled differently, without strong actin adhesion. In cells, LAT condensates lost Nck as radial actin transitioned to the concentric network, and engineered condensates constitutively binding actin moved aberrantly. Our data show that Nck and WASP form a clutch between LAT condensates and actin in vitro and suggest that compositional changes may enable condensate movement by distinct actin networks in different regions of the IS.

}, issn = {2050-084X}, doi = {10.7554/eLife.42695}, author = {Ditlev, Jonathon A and Vega, Anthony R and K{\"o}ster, Darius Vasco and Su, Xiaolei and Tani, Tomomi and Lakoduk, Ashley M and Vale, Ronald D and Mayor, Satyajit and Jaqaman, Khuloud and Rosen, Michael K} } @article {53177, title = {Cone snail prolyl-4-hydroxylase α-subunit sequences derived from transcriptomic data and mass spectrometric analysis of variable proline hydroxylation in C. amadis venom.}, journal = {J Proteomics}, volume = {194}, year = {2019}, month = {2019 Mar 01}, pages = {37-48}, abstract = {

Putative prolyl-4-hydroxylase (P4H) α-subunit sequences have been extracted by mining transcriptomic data obtained from seven cone snail species C. amadis, C. monile, C. araneosus, C. miles, C. litteratus, C. frigidus, and C. ebraeus. Sequences ranging from 518 to 559 residues have been compared with representative animal P4H sequences. The α-subunit consists of an N-terminus double domain, involved in dimerization and substrate binding, while the C-terminus contains the catalytic domain. Definitive functional annotation of the cone snail sequences has been achieved by an analysis of conserved residues responsible for catalytic function, specific conformational features, and subunit interactions, using two independent structures of the double domain, and the catalytic domain, previously reported in the literature. The variability of proline hydroxylation in conotoxins is illustrated by a mass spectrometric analysis of C. amadis venom. Site specific hydroxylation and the presence of peptides with multiple proline residues, resistant to modification, suggests that sequence and conformational effects may determine the substrate specificity of the Conus prolyl-4-hydroxylases. SIGNIFICANCE: Proline hydroxylation is a widely observed post translational modification, with collagen being the pre-eminent example. Hydroxylation of proline is also widely observed in conotoxins, which are a major component of marine cone snail venom. This paper describes newly identified prolyl-4-hydroxylase sequences, using transcriptome data from seven Conus species. The predicted functional annotation of prolyl-4-hydroxylase sequences was carried out using two available crystal structures of independent domains. The mass spectrometric characterisation of proline/hydroxyproline containing peptides in C. amadis venom confirms sequence specific hydroxylation in Conus venom as shown previously by others.

}, issn = {1876-7737}, doi = {10.1016/j.jprot.2018.12.028}, author = {Vijayasarathy, M and Balaram, P} } @article {53181, title = {A conserved and buried edge-to-face aromatic interaction in Small Ubiquitin-like Modifier (SUMO) has a role in SUMO stability and function.}, journal = {J Biol Chem}, year = {2019}, month = {2019 Mar 01}, abstract = {

Aromatic amino acids buried at a protein{\textquoteright}s core are often involved in mutual paired interactions. Ab initio energy calculations have highlighted that the conformational orientations and the effects of substitutions are important for stable aromatic interactions among aromatic rings, but studies in the context of a protein{\textquoteright}s fold and function are elusive. Small ubiquitin-like modifier (SUMO) is a common post-translational modifier that affects diverse cellular processes. Here, we report that a highly conserved aromatic triad of three amino acids, Phe36-Tyr51-Phe64, is a unique SUMO signature that is absent in other ubiquitin-like homologous folds. We found that a specific edge-to-face conformation between the Tyr51-Phe64 pair of interacting aromatics is vital to the fold and stability of SUMO. Moreover, the noncovalent binding of SUMO-interacting motif (SIM) at the SUMO surface was critically dependent on the paired aromatic interactions buried at the core. NMR structural studies revealed that perturbation of the Tyr51-Phe64 conformation disrupts several long-range tertiary contacts in SUMO, leading to a heterogeneous and dynamic protein with attenuated SUMOylation both in vitro and in cells. A subtle perturbation of the edge-to-face conformation by a Tyr-to-Phe substitution significantly decreased stability, SUMO/SIM affinity, and the rate of SUMOylation. Our results highlight that absolute co-conservation of specific aromatic pairs inside the SUMO protein core has a role in its stability and function.

}, issn = {1083-351X}, doi = {10.1074/jbc.RA118.006642}, author = {Chatterjee, Kiran Sankar and Tripathi, Vasvi and Das, Ranabir} } @article {65308, title = {Constraints on somite formation in developing embryos.}, journal = {J R Soc Interface}, volume = {16}, year = {2019}, month = {2019 Sep 27}, pages = {20190451}, abstract = {

Segment formation in vertebrate embryos is a stunning example of biological self-organization. Here, we present an idealized framework, in which we treat the presomitic mesoderm (PSM) as a one-dimensional line of oscillators. We use the framework to derive constraints that connect the size of somites, and the timing of their formation, to the growth of the PSM and the gradient of the somitogenesis clock period across the PSM. Our analysis recapitulates the observations made recently in cultures of mouse PSM cells, and makes predictions for how perturbations, such as increased Wnt levels, would alter somite widths. Finally, our analysis makes testable predictions for the shape of the phase profile and somite widths at different stages of PSM growth. In particular, we show that the phase profile is robustly concave when the PSM length is steady and slightly convex in an important special case when it is decreasing exponentially. In both cases, the phase profile scales with the PSM length; in the latter case, it scales dynamically. This has important consequences for the velocity of the waves that traverse the PSM and trigger somite formation, as well as the effect of errors in phase measurement on somite widths.

}, issn = {1742-5662}, doi = {10.1098/rsif.2019.0451}, author = {Juul, Jonas S and Jensen, Mogens H and Krishna, Sandeep} } @article {55795, title = {Contributions of the Cerebellum for Predictive and Instructional Control of Movement.}, journal = {Curr Opin Physiol}, volume = {8}, year = {2019}, month = {2019 Apr}, pages = {146-151}, abstract = {

The cerebellum with its layered structure and stereotyped and conserved connectivity has long puzzled neurobiologists. While it is well established that the cerebellum functions in regulating balance, motor coordination and motor learning, how it achieves these end results has not been very clear. Recent technical advances have made it possible to tease apart the contributions of cerebellar cell types to movement in behaving animals. We review these studies focusing on the three major cerebellar cell types, namely: granule cells, Purkinje neurons and the cells of the deep cerebellar nuclei. Further, we also review our current understanding of cortico-cerebellar and basal ganglia-cerebellar interactions that play vital roles in motor planning and motor learning.

}, issn = {2468-8673}, doi = {10.1016/j.cophys.2019.01.011}, author = {Narayanan, Sriram and Thirumalai, Vatsala} } @article {60331, title = {C{\textendash}H Arylation of N-Heteroarenes under Metal-Free Conditions and its Application towards the Synthesis of Pentabromo- and Pentachloropseudilins}, journal = {EUROPEAN JOURNAL OF ORGANIC CHEMISTRY}, volume = {2019}, year = {2019}, month = {06/2019}, pages = {3591-3598}, abstract = {

Herein, we have developed a metal-free and mild condition for the synthesis of 2-arylated heteroarenes. The complex forming property and charge transfer property of phenothiazine expanded its application towards catalysis The optimized condition has been successfully employed for the synthesis important marine natural product namely pentabromo/chloropseudilins (PBP/PCP). The synthesized Pentachloropseudilin (PCP) has been shown to phenocopy the effect of Myosin1c depletion which provides a strong justification for the use of PCP as a specific probe for Myosin 1 function in cells.

}, doi = {10.1002/ejoc.201900353}, author = {Kumar, M and Sharma, S and Sil, P and Kushwaha, M and Mayor, S and Vishwakarma, RA and Singh, PP} } @article {69320, title = {Data enabled prediction analysis assigns folate/biopterin transporter (BT1) family to 36 hypothetical membrane proteins in Leishmania donovani.}, journal = {Bioinformation}, volume = {15}, year = {2019}, month = {2019}, pages = {697-708}, abstract = {

Leishmaniasis is a neglected tropical disease caused by the pathogenic protozoan Leishmania donovani and it is transmitted by an infected sand fly. Approximately 0.4 million cases of Visceral Leishmaniasis are reported across the globe every year, of which 67\% is from the Indian subcontinent. The currently available drugs have not been effective owing to their high toxicity levels, inadequate specificity, drug resistance, extended treatment periods and/or prohibitive prices. For this reason, hypothetical proteins in this pathogen, which constitute about 67\% of its proteome, must be distinctly characterized and studied for their potential role as drug targets for Leishmaniasis. Domain information from PFAM and functional information from GO has been used to assign putative functions to 36 hypothetical membrane proteins in this protozoan. Furthermore, as a case study, we have performed a thorough sequence level characterization of a hypothetical protein E9BPD7 from the BT1 family of membrane proteins that transports folate/biopterin. Phylogenetic analyses of E9BPD7 have revealed interesting evolutionary correlations to BT1 family and MFS superfamily, which have significant roles in a number of diseases and drug resistance pathways.

}, issn = {0973-2063}, doi = {10.6026/97320630015697}, author = {Ravooru, Nithin and Paul, Ojal Sarah and Nagendra, Holenarasipur Gundurao and Sathyanarayanan, Nitish} } @article {69319, title = {Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Oct 22}, abstract = {

The deamidase OspI from enteric bacteria deamidates a glutamine residue in the host ubiquitin-conjugating enzyme UBC13 and converts it to glutamate (Q100E). Consequently, its polyubiquitination activity in complex with the RING-finger ubiquitin ligase TRAF6 and the downstream NF-κB inflammatory response is silenced. The precise role of deamidation in silencing the UBC13/TRAF6 complex is unknown. We report that deamidation inhibits the interaction between UBC13 and TRAF6 RING-domain (TRAF6) by perturbing both the native and transient interactions. Deamidation creates a new intramolecular salt-bridge in UBC13 that competes with a critical intermolecular salt-bridge at the native UBC13/TRAF6 interface. Moreover, the salt-bridge competition prevents transient interactions necessary to form a typical UBC13/RING complex. Repulsion between E100 and the negatively charged surface of RING also prevents transient interactions in the UBC13/RING complex. Our findings highlight a mechanism wherein a post-translational modification perturbs the conformation and stability of transient complexes to inhibit protein-protein association.

}, issn = {2050-084X}, doi = {10.7554/eLife.49223}, author = {Mohanty, Priyesh and Agrata, Rashmi and Habibullah, Batul Ismail and G S, Arun and Das, Ranabir} } @article {48884, title = {Decoding systems biology of plant stress for sustainable agriculture development and optimized food production.}, journal = {Prog Biophys Mol Biol}, volume = {145}, year = {2019}, month = {2018 Dec 15}, pages = {19-39}, abstract = {

Plants are essential facilitators of human life on planet earth. Plants play a critical functional role in mediating the quality of air, availability of food and the sustainability of agricultural resources. However, plants are in constant interaction with its environment and often hampered by various types of stresses like biotic and abiotic ones. Biotic stress is a significant reason for crop-loss and causes yield loss in the range of 31-42\%, post-harvest loss due to biotic stress is in the range of 6-20\%, and abiotic stress causes 6-20\% of the crop damage. Recognizing the molecular factors driving plant stress-related events, and developing molecular strategies to aid plants to tolerate, resist or adapt to biotic and abiotic stress are critical for sustainable agriculture practice. In this review, we discuss how recent advances in bioinformatics, plant genomics, and data science could help to improve our understanding of plant stress biology and improve the scale of global food production. We present various areas of scientific and technological advances, such as increased availability of genomics data through whole genome sequencing that require attention. We also discuss emerging techniques including CRISPR-Cas9 based genome engineering systems to develop plant varieties that can handle combinatorial stress signals. Growing trend of converging multiple omics technologies and availability of accurate, multi-scale models of plant stress through the study of orthologs and synteny studies, would improve our knowledge of how plants perceive, respond, and manage stress to thrive as resilient crop species and thus help to reduce global food crisis.

}, issn = {1873-1732}, doi = {10.1016/j.pbiomolbio.2018.12.002}, author = {Shameer, Khader and Naika, Mahantesha B N and Shafi, K Mohamed and Sowdhamini, Ramanathan} } @article {24494, title = {Dendrites, Deep Learning, and Sequences in the Hippocampus.}, journal = {Hippocampus}, volume = {29}, year = {2019}, month = {2017 Oct 12}, pages = {239-251}, abstract = {

The hippocampus places us both in time and space. It does so over remarkably large spans: milliseconds to years, and centimeters to kilometers. This works for sensory representations, for memory, and for behavioral context. How does it fit in such wide ranges of time and space scales, and keep order among the many dimensions of stimulus context? A key organizing principle for a wide sweep of scales and stimulus dimensions is that of order in time, or sequences. Sequences of neuronal activity are ubiquitous in sensory processing, in motor control, in planning actions, and in memory. Against this strong evidence for the phenomenon, there are currently more models than definite experiments about how the brain generates ordered activity. The flip side of sequence generation is discrimination. Discrimination of sequences has been extensively studied at the behavioral, systems, and modeling level, but again physiological mechanisms are fewer. It is against this backdrop that I discuss two recent developments in neural sequence computation, that at face value share little beyond the label {\textquoteright}neural{\textquoteright}. These are dendritic sequence discrimination, and deep learning. One derives from channel physiology and molecular signaling, the other from applied neural network theory - apparently extreme ends of the spectrum of neural circuit detail. I suggest that each of these topics has deep lessons about the possible mechanisms, scales, and capabilities of hippocampal sequence computation. This article is protected by copyright. All rights reserved.

}, issn = {1098-1063}, doi = {10.1002/hipo.22806}, author = {Bhalla, Upinder S} } @article {59741, title = {Differential effects of unipolar versus bipolar depression on episodic memory updating.}, journal = {Neurobiol Learn Mem}, volume = {161}, year = {2019}, month = {2019 05}, pages = {158-168}, abstract = {

Episodic memories, when reactivated, can be modified or updated by new learning. Since such dynamic memory processes remain largely unexplored in psychiatric disorders, we examined the impact of depression on episodic memory updating. Unipolar and bipolar depression patients, and age/education matched controls, first learned a set of objects (List-1). Two days later, participants in all three groups were either reminded of the first learning session or not followed by the learning of a new set of objects (List-2). Forty-eight hours later, List-1 recall was impaired in unipolar and bipolar patients compared to control participants. Further, as expected, control participants who received a reminder spontaneously recalled items from List-2 during recall of List-1, indicative of an updated List-1 memory. Such spontaneous intrusions were also seen in the unipolar and bipolar patients that received the reminder, suggesting that memory updating was unaffected in these two patient groups despite impaired recall of List 1. Unexpectedly, we observed a trend towards higher intrusions, albeit statistically insignificant, not only in the reminder but also in the no-reminder subgroups of bipolar patients. We probed this further in a second cohort by testing recall of List-2, which was also impaired in both depression groups. Again bipolar patients showed intrusions, but this time in the reverse order from List-1 into List-2, independent of a reminder. Taken together, despite impaired recall, updating of episodic memories was intact and unidirectional in unipolar depression. In contrast, indiscriminate updating, as evidenced by bidirectional interference between episodic memories, was seen in bipolar depression. These findings reveal a novel distinction between unipolar versus bipolar depression using a reactivation-dependent memory updating paradigm.

}, issn = {1095-9564}, doi = {10.1016/j.nlm.2019.04.008}, author = {Dongaonkar, Bhaktee and Hupbach, Almut and Nadel, Lynn and Chattarji, Sumantra} } @article {53989, title = {Dimensions of ant diversity on a small tropical island}, journal = {INSECT CONSERVATION AND DIVERSITY}, volume = {12}, year = {2019}, month = {03/2019}, pages = {161-171}, abstract = {
  1. Recent appreciation of the multidimensional nature of biodiversity has prompted biologists to examine the taxonomic, functional, and phylogenetic attributes of natural communities. Simultaneous consideration of such multiple diversity dimensions provides valuable insights into various community assembly processes.
  2. We studied the alpha and beta components of ant diversity on a simple island landscape dominated by adjacent but abiotically distinct evergreen (humid \& dense canopy) and littoral (dry \& sparse canopy) forest habitats. We sought to (i) describe and examine interrelationships of ant diversity dimensions, and (ii) identify potential processes structuring ant communities by comparing the diversity patterns of observed and randomly generated communities.
  3. We found that the drier littoral habitat had lower ant species richness and non-random community composition, but had similar functional diversity as evergreen forests. This result is in contrast with previous studies comparing intact and human-altered habitats that reported severe loss of ant functional diversity with reduced richness. In our study, the functional similarity between habitats was maintained because communities in littoral forests were functionally overdispersed than expected by chance. We suggest that competition and/or thermal tolerance of ants may drive overdispersion of littoral ant communities.
  4. At the small spatial scale of our island, phylogenetic diversity was a poor predictor of habitat differences despite significant phylogenetic signal in functional traits and non-random functional diversity patterns. Our work highlights the need for a broad range of studies comparing multidimensional diversity in adjacent habitats that would provide a baseline for interpreting community-level changes due to anthropogenic pressures.
}, doi = {10.1111/icad.12326}, author = {Agavekar, Gaurav and Agashe, Deepa and Economo, EP} } @article {70232, title = {Disrupting butterfly caterpillar microbiomes does not impact their survival and development.}, journal = {Proc Biol Sci}, volume = {286}, year = {2019}, month = {2019 Dec 18}, pages = {20192438}, abstract = {

Associations with gut microbes are believed to play crucial roles in the physiology, immune function, development and behaviour of insects. However, microbiome sequencing has recently suggested that butterflies are an anomaly, because their microbiomes do not show strong host- and developmental stage-specific associations. We experimentally manipulated butterfly larval gut microbiota and found that disrupting gut microbes had little influence on larval survival and development. Larvae of the butterflies and that fed on chemically sterilized or antibiotic-treated host plant leaves had significantly reduced bacterial loads, and their gut bacterial communities were disrupted substantially. However, neither host species treated this way suffered a significant fitness cost: across multiple experimental blocks, treated and control larvae had similar survival, growth and development. Furthermore, re-introducing microbes from the excreta of control larvae did not improve larval growth and survival. Thus, these butterfly larvae did not appear to rely on specialized gut bacteria for digestion, detoxification, biomass accumulation and metamorphosis. Our experiments thus show that dependence on gut bacteria for growth and survival is not a universal phenomenon across insects. Our findings also caution that strategies which target gut microbiomes may not always succeed in controlling Lepidopteran pests.

}, issn = {1471-2954}, doi = {10.1098/rspb.2019.2438}, author = {Phalnikar, Kruttika and Kunte, Krushnamegh and Agashe, Deepa} } @article {65307, title = {Diversity matters: Effects of density compensation in pollination service during rainfall shift.}, journal = {Ecol Evol}, volume = {9}, year = {2019}, month = {2019 Sep}, pages = {9701-9711}, abstract = {

Extreme weather events are increasing in frequency due to the warming climate. Such extremities can jeopardize ecosystem services and create economic imbalances. Tropical developing countries are predicted to suffer the maximum consequences of such events.We examined the impact of such an event-extreme rainfall fluctuation-on a critical ecosystem service-pollination, which can be intricately linked to a country{\textquoteright}s economy. We performed this study in a dominant peri-urban vegetable hub of an agriculture-dependent developing country.We found that the yield of all pollinator-dependent crops grown across a large spatial scale (district) over multiple years (six) drastically declined with the decrease in rainfall.At the local scale, we found that the dominant crop (representative horticultural crop) had a significant drop in yield during drought, likely due to the production of fewer female flowers and a significant shift in the pollinator community.We found that sp. (one of the four pollinators) was the critical pollinator positively influencing fruit-to-flower ratio (FFR) (an indicator of pollination service) in the normal rainfall year. However, despite its sharp decline during drought, the FFR remained unaffected. We found that during drought, was crucial in maintaining FFR and compensated for the decline of the critical pollinator across 67\% farmlands.Our study demonstrates the role of ecosystem stabilizing mechanism rescuing the crucial ecosystem service during climatic variability over the temporal scale.

}, issn = {2045-7758}, doi = {10.1002/ece3.5500}, author = {Mukherjee, Ronita and Deb, Rittik and Devy, Soubadra M} } @article {43847, title = {Does retinoic acid reverse cell cycle dysregulation in Alzheimer{\textquoteright}s disease lymphocytes?}, journal = {Asian J Psychiatr}, volume = {39}, year = {2019}, month = {2018 Aug 16}, pages = {174-177}, abstract = {

Aberrant re-entry of neurons into cell cycle appears to be an early event in Alzheimer{\textquoteright}s disease (AD) and targeting this dysregulation may have therapeutic potential. We have examined whether cell cycle dysregulation in AD can be detected using patient and control derived B-lymphocytes. Cell cycle analysis using flow cytometry demonstrated that cell cycle dysregulation occurs in AD lymphocytes, with a significant difference in the distribution of cells in G0/G1, S and G2/M phases of cell cycle as compared to control lymphocytes. Using global gene expression analysis by RNA sequencing and cell cycle analysis, we examined the role of Retinoic Acid (RA), a candidate molecule predicted to be of therapeutic potential in cell cycle dysregulation associated with AD. CCND1, CCNE2, E2F transcription factors which are known to be dysregulated in AD were among the 32 genes that showed differential expression in response to RA treatment thus suggesting a protective role of RA. However, the cell cycle analysis demonstrated that RA did not reverse the cellular phenotype in AD lymphocytes. This suggests that though RA might have a protective role by influencing the expression of cell cycle genes, it might not be able to arrest abnormal re-entry into cell cycle.

}, issn = {1876-2026}, doi = {10.1016/j.ajp.2018.08.010}, author = {Ashok, Aparna and Naaz, Safoora and Kota, Lakshmi Narayanan and Sen, Somdatta and Purushottam, Meera and Faruq, Mohammed and Kumari, Renu and Yadav, Vinod and Kannan, Ramakrishnan and Jain, Sanjeev and Panicker, Mitradas M and Viswanath, Biju} } @article {62770, title = {Droughts and the ecological future of tropical savanna vegetation}, journal = {JOURNAL OF ECOLOGY}, volume = {107}, year = {2019}, month = {07/2019}, pages = {1531-1549}, doi = {10.1111/1365-2745.13195}, author = {Sankaran, Mahesh and Staver, C} } @article {53175, title = {Dry-forest tree species with large seeds and low stem specific density show greater survival under drought}, journal = {JOURNAL OF TROPICAL ECOLOGY}, volume = {35}, year = {2019}, month = {01/2019}, pages = {26-33 }, author = {Krishnan, L and Barua, D and Sankaran, M} } @article {51247, title = {Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.}, journal = {Proc Natl Acad Sci U S A}, volume = {116}, year = {2019}, month = {2019 Jan 15}, pages = {1027-1032}, abstract = {

Merkel cell polyomavirus (MCV) contributes to approximately 80\% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contrast, virus-negative MCC contains inactivating mutations in TP53 and RB1. While the MCV-truncated LT can bind and inhibit RB, it does not bind p53. We report here that MCV LT binds to RB, leading to increased levels of ARF, an inhibitor of MDM2, and activation of p53. However, coexpression of ST reduced p53 activation. MCV ST recruits the MYC homologue MYCL (L-Myc) to the EP400 chromatin remodeler complex and transactivates specific target genes. We observed that depletion of EP400 in MCV-positive MCC cell lines led to increased p53 target gene expression. We suspected that the MCV ST-MYCL-EP400 complex could functionally inactivate p53, but the underlying mechanism was not known. Integrated ChIP and RNA-sequencing analysis following EP400 depletion identified MDM2 as well as CK1α, an activator of MDM4, as target genes of the ST-MYCL-EP400 complex. In addition, MCV-positive MCC cells expressed high levels of MDM4. Combining MDM2 inhibitors with lenalidomide targeting CK1α or an MDM4 inhibitor caused synergistic activation of p53, leading to an apoptotic response in MCV-positive MCC cells and MCC-derived xenografts in mice. These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.

}, issn = {1091-6490}, doi = {10.1073/pnas.1818798116}, author = {Park, Donglim Esther and Cheng, Jingwei and Berrios, Christian and Montero, Joan and Cort{\'e}s-Cros, Marta and Ferretti, St{\'e}phane and Arora, Reety and Tillgren, Michelle L and Gokhale, Prafulla C and DeCaprio, James A} } @article {60607, title = {Dynamic expression of tRNA-derived small RNAs define cellular states.}, journal = {EMBO Rep}, volume = {20}, year = {2019}, month = {2019 Jul}, pages = {e47789}, abstract = {

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell-state transitions remain unclear. Expression analysis of tsRNAs in distinct heterologous cell and tissue models of stem vs. differentiated states revealed a differentiation-dependent enrichment of 5{\textquoteright}-tsRNAs. We report the identification of a set of 5{\textquoteright}-tsRNAs that is upregulated in differentiating mouse embryonic stem cells (mESCs). Notably, interactome studies with differentially enriched 5{\textquoteright}-tsRNAs revealed a switch in their association with "effector" RNPs and "target" mRNAs in different cell states. We demonstrate that specific 5{\textquoteright}-tsRNAs can preferentially interact with the RNA-binding protein, Igf2bp1, in the RA-induced differentiated state. This association influences the transcript stability and thereby translation of the pluripotency-promoting factor, c-Myc, thus providing a mechanistic basis for how 5{\textquoteright}-tsRNAs can modulate stem cell states in mESCs. Together our study highlights the role of 5{\textquoteright}-tsRNAs in defining distinct cell states.

}, issn = {1469-3178}, doi = {10.15252/embr.201947789}, author = {Krishna, Srikar and Yim, Daniel Gr and Lakshmanan, Vairavan and Tirumalai, Varsha and Koh, Judice Ly and Park, Jung Eun and Cheong, Jit Kong and Low, Joo Leng and Lim, Michelle Js and Sze, Siu Kwan and Shivaprasad, Padubidri and Gulyani, Akash and Raghavan, Srikala and Palakodeti, Dasaradhi and DasGupta, Ramanuj} } @article {56656, title = {Dynamics and stability of running on rough terrains.}, journal = {R Soc Open Sci}, volume = {6}, year = {2019}, month = {2019 Mar}, pages = {181729}, abstract = {

Stability of running on rough terrain depends on the propagation of perturbations due to the ground. We consider stability within the sagittal plane and model the dynamics of running as a two-dimensional body with alternating aerial and stance phases. Stance is modelled as a passive, impulsive collision followed by an active, impulsive push-off that compensates for collisional losses. Such a runner has infinitely many strategies to maintain periodic gaits on flat ground. However, these strategies differ in how perturbations due to terrain unevenness are propagated. Instabilities manifest as tumbling (orientational instability) or failing to maintain a steady speed (translational instability). We find that open-loop strategies that avoid sensory feedback are sufficient to maintain stability on step-like terrains with piecewise flat surfaces that randomly vary in height. However, these open-loop runners lose orientational stability on rough terrains whose slope also varies randomly. The orientational instability is significantly mitigated by minimizing the tangential collision, which typically requires sensory information and anticipatory strategies such as leg retraction. By analysing the propagation of perturbations, we derive a single dimensionless parameter that governs stability. This parameter provides guidelines for the design and control of both biological and robotic runners.

}, issn = {2054-5703}, doi = {10.1098/rsos.181729}, author = {Dhawale, Nihav and Mandre, Shreyas and Venkadesan, Madhusudhan} } @article {59713, title = {EcRBPome: a comprehensive database of all known E. coli RNA-binding proteins.}, journal = {BMC Genomics}, volume = {20}, year = {2019}, month = {2019 May 22}, pages = {403}, abstract = {

The repertoire of RNA-binding proteins (RBPs) in bacteria play a crucial role in their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome. It contains RBPs recorded from 614 complete E. coli proteomes available in the RefSeq database (as of October 2018). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download. To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community.

}, issn = {1471-2164}, doi = {10.1186/s12864-019-5755-5}, author = {Ghosh, Pritha and Joshi, Adwait and Guita, Niang and Offmann, Bernard and Sowdhamini, R} } @article {74435, title = {Edge effects reduce α-diversity but not β-diversity during community assembly in a human-modified tropical forest.}, journal = {Ecol Appl}, volume = {29}, year = {2019}, month = {2019 12}, pages = {e01996}, abstract = {

Edge effects can alter the spatial organization of diversity in fragmented habitats. For tropical forests, however, there has been large variation in the strength and direction of such effects reported by different studies. For long-lived organisms like trees, one reason for inconsistent patterns might be due to most studies having examined patterns of diversity and compositional variation in older life stages that bear the legacy of a forest past. Younger life stages can reveal ongoing processes of assembly, but multi-stage examinations are rare. For seedling, sapling, and adult life stages of trees in a human-modified wet tropical forest in the Western Ghats Biodiversity Hotspot (India), we examined how proximity to forest edges (edge influence) modified the spatial organization of diversity. Specifically, for each life stage we tested whether edge influence led to loss of α- and γ-diversity and decreased β-diversity in this landscape. We found lower α- and γ-diversity closer to forest edges, but only for seedlings. Seedling composition at 90-100\ m from forest edges diverged from composition of sites within 60\ m, suggesting that edge influence restricted the recruitment of some species to interior sites. In contrast, β-diversity was greater near edges than interior forest for all life stages and most prominently for seedlings. Furthermore, β-diversity at edges was primarily driven by species turnover, suggesting either marked species-environment associations or dispersal limitation. Low turnover at 90-100\ m implies that β-diversity arose from stochastic fluctuations in occurrences and abundances of the same species set. Overall, we find that high β-diversity structured spatial patterns of diversity near edges, but recruitment bottlenecks are likely to reduce alpha diversity of forest fragments. Our results also corroborate the need to maintain sufficiently large areas of tropical forest free from edge effects to avoid the loss of interior forest species. To improve landscape-scale diversity of fragmented landscapes, restoration efforts should focus on recovery of species that are unable to regenerate near forest edges.

}, keywords = {Aged, Biodiversity, Ecosystem, Forests, Humans, India, Trees, Tropical Climate}, issn = {1051-0761}, doi = {10.1002/eap.1996}, author = {Krishnadas, Meghna and Kumar, Arun N and Comita, Liza S} } @article {47059, title = {Effectiveness and efficiency of two distinct mechanisms for take-off in a derbid planthopper insect.}, journal = {J Exp Biol}, volume = {222}, year = {2019}, month = {01/2019}, abstract = {

Analysis of the kinematics of take-off in the planthopper (Hemiptera, Fulgoroidea, family Derbidae) from high speed videos showed that individual insects used two distinct mechanisms involving different appendages. The first was a fast take-off (55.7\% of 106 take-offs by 11 insects) propelled by a synchronised movement of the two hind legs and without participation of the wings. The body was accelerated in 1 ms or less to a mean take-off velocity of 1.7 m s while experiencing average forces of more than 150 times gravity. The power required from the leg muscles implicated a power-amplification mechanism. Such take-offs propelled the insect along its trajectory a mean distance of 7.9 mm in the first 5 ms after take-off. The second and slower take-off mechanism (44.3\% of take-offs) was powered by beating movements of the wings alone with no discernible contribution from the hind legs. The resulting mean acceleration time was 16 times slower at 17.3 ms, the mean final velocity was six times lower at 0.27 m s, the forces experienced were 80 times lower and the distance moved in 5 ms after take-off was 7 times shorter. The power requirements could be readily met by direct muscle contraction. The results suggest a testable hypothesis that the two mechanisms serve distinct behavioural actions; the fast take-offs could enable escape from predators; the slow take-offs that exert much lower ground reaction forces could enable take-off from more flexible substrates while also displacing the insect in a slower and more controllable trajectory.

}, issn = {1477-9145}, doi = {10.1242/jeb.191494}, author = {Burrows, M and Ghosh, A and Yeshwanth, H M and Dorosenko, M and Sane, S P} } @article {66085, title = { Effects of extractive use on forest birds in Western Himalayas: Role of local and landscape factors }, journal = {FOREST ECOLOGY AND MANAGEMENT}, volume = {448}, year = {2019}, month = {09/2019}, pages = {457-465}, abstract = {

Rural populations in developing countries depend on forests for fuelwood, fodder and other non-timber forest products. Such dependence has significant effects on faunal diversity and composition, primarily due to alteration of vegetation structure. While earlier studies have assessed the consequences of extractive activities for forest fauna, very few simultaneously acknowledge the role of landscape context, which includes agricultural land-uses and managed forests. This study was carried out in oak-dominated forests located in the middle elevations of the Western Himalayas to investigate effects of extractive activities on avifaunal communities, taking into account the role of landscape composition. Birds were sampled at 74 sites, six times each, over two seasons using fixed-radius point counts. We analysed avian species richness, abundance, composition and guild abundances (based on foraging and habitat preference) as a function of vegetation structure and proportion of dense oak forest around each site. Our results suggest that extractive activities in forests can result in reduced species richness, abundance and altered composition of forest avifauna, brought about by changes in vegetation structure. We also find that these effects may be intensified by the loss of dense oak forests in the landscape. Insectivorous birds and forest specialists were most sensitive to extractive activities and landscape composition. Decreasing canopy cover and proportion of oak forest in the landscape had strong negative effects on insectivorous and forest specialist species. Other local factors such as vertical stratification and understory density also had effects on these avian guilds. Our study indicates that in order to conserve bird species in an increasingly human-dominated landscape of the Western Himalayas, it may be necessary to control extractive activities that affect forest structure as well as retain protected forest stands within a continuum of harvested forest and agricultural landscapes.

}, doi = {10.1016/j.foreco.2019.06.033}, author = {Menon, T and Sridhar, H and Shahabuddin, G} } @article {65295, title = {Empowering conservation practice with efficient and economical genotyping from poor quality samples.}, journal = {Methods Ecol Evol}, volume = {10}, year = {2019}, month = {2019 Jun}, pages = {853-859}, abstract = {

Moderate- to high-density genotyping (100 + SNPs) is widely used to determine and measure individual identity, relatedness, fitness, population structure and migration in wild populations.However, these important tools are difficult to apply when high-quality genetic material is unavailable. Most genomic tools are developed for high-quality DNA sources from laboratory or medical settings. As a result, most genetic data from market or field settings is limited to easily amplified mitochondrial DNA or a few microsatellites.To enable genotyping in conservation contexts, we used next-generation sequencing of multiplex PCR products from very low-quality DNA extracted from faeces, hair and cooked samples. We demonstrated utility and wide-ranging potential application in endangered wild tigers and tracking commercial trade in Caribbean queen conch.We genotyped 100 SNPs from degraded tiger samples to identify individuals, discern close relatives and detect population differentiation. Co-occurring carnivores do not amplify (e.g. Indian wild dog/dhole) or are monomorphic (e.g. leopard). Sixty-two SNPs from conch fritters and field-collected samples were used to test relatedness and detect population structure.We provide proof of concept for a rapid, simple, cost-effective and scalable method (for both samples and number of loci), a framework that can be applied to other conservation scenarios previously limited by low-quality DNA samples. These approaches provide a critical advance for wildlife monitoring and forensics, open the door to field-ready testing, and will strengthen the use of science in policy decisions and wildlife trade.

}, issn = {2041-210X}, doi = {10.1111/2041-210X.13173}, author = {Natesh, Meghana and Taylor, Ryan W and Truelove, Nathan K and Hadly, Elizabeth A and Palumbi, Stephen R and Petrov, Dmitri A and Ramakrishnan, Uma} } @article {67826, title = {"Endangered or an artifact of unsound taxonomy? Case of the critically~endangered bush frog Philautus sanctisilvaticus Das and Chanda, 1997".}, journal = {Zootaxa}, volume = {4683}, year = {2019}, month = {2019 Oct 10}, pages = {zootaxa.4683.4.6}, abstract = {

We investigated the phylogenetic relationship of the Critically Endangered bush frog Philautus sanctisilvaticus Das and Chanda, 1997 and other species distributed across the fragmented forests of Deccan Peninsula and the northern Eastern Ghats. A short fragment of the mitochondrial 16S rRNA gene was employed to assess phylogenetic relationships across Philautus sanctisilvaticus Das and Chanda, 1997, Raorchestes terebrans (Das and Chanda, 1998) and Philautus similipalensis Dutta, 2003. All sequenced specimens, including material from near the type localities of P. sanctisilvaticus (Amarkantak) and P. similipalensis (Simlipal) were genetically extremely similar, with pairwise uncorrected distances 1\% in the 16S gene, and were phylogenetically placed within the genus Raorchestes. The results based on morphology are ambiguous and do not go hand in hand with molecular data, which however do not provide support for a three species hypothesis either. our findings advocate the need for making nomenclatural amendments. Philautus sanctisilvaticus Das and Chanda, 1997, is the first available nomen for this taxon, and we propose to include this species in Raorchestes as Raorchestes sanctisilvaticus (Das and Chanda, 1997), and to consider the nomina Philautus terebrans Das and Chanda, 1998 syn. nov. and Philautus similipalensis Dutta, 2003 syn. nov. as junior subjective synonyms for this nomen following the Principle of Priority in article 23.1 of the ICZN. The findings are notable from the point of conservation of the species and present a novel case with remarkable genetic homogeneity across the fragmented forests of Deccan Peninsula and Eastern Ghats.

}, keywords = {Animals, Anura, Fishes, Phylogeny, RNA, Ribosomal, 16S}, issn = {1175-5334}, doi = {10.11646/zootaxa.4683.4.6}, author = {Mirza, Zeeshan A and Warekar, Priya and Mohapatra, Pratyush P and Raju, David and Patil, Pranad and Dutta, Sushil K and Pal, Saunak} } @article {60615, title = {Endophytic Bacteria in Plant Salt Stress Tolerance: Current and Future Prospects}, journal = {Journal of Plant Growth Regulation}, volume = {38}, year = {2019}, month = {06/2019}, pages = {650{\textendash}668 }, abstract = {

Soil salinity is a major limiting factor for crop productivity worldwide and is continuously increasing owing to climate change. A wide range of studies and practices have been performed to induce salt tolerance mechanisms in plants, but their result in crop improvement has been limited due to lack of time and money. In the current scenario, there is increasing attention towards habitat-imposed plant stress tolerance driven by plant-associated microbes, either rhizospheric and/or endophytic. These microbes play a key role in protecting plants against various environmental stresses. Therefore, the use of plant growth-promoting microbes in agriculture is a low-cost and eco-friendly technology to enhance crop productivity in saline areas. In the present review, the authors describe the functionality of endophytic bacteria and their modes of action to enhance salinity tolerance in plants, with special reference to osmotic and ionic stress management. There is concrete evidence that endophytic bacteria serve host functions, such as improving osmolytes, anti-oxidant and phytohormonal signaling and enhancing plant nutrient uptake efficiency. More research on endophytes has enabled us to gain insights into the mechanism of colonization and their interactions with plants. With this information in mind, the authors tried\ to solve\ the following questions: (1) how do benign endophytes ameliorate salt stress in plants? (2) What type of physiological changes incur in plants under salt stress conditions? And (3), what type of determinants produced by endophytes will be helpful in plant growth promotion under salt stress?

}, doi = {10.1007/s00344-018-9880-1}, author = {Vaishnav, A and Shukla, AK and Sharma, A and Kumar, R and Choudhary, DK} } @article {62763, title = {ER-Ca2+ sensor STIM regulates neuropeptides required for development under nutrient restriction in Drosophila.}, journal = {PLoS One}, volume = {14}, year = {2019}, month = {2019}, pages = {e0219719}, abstract = {

Neuroendocrine cells communicate via neuropeptides to regulate behaviour and physiology. This study examines how STIM (Stromal Interacting Molecule), an ER-Ca2+ sensor required for Store-operated Ca2+ entry, regulates neuropeptides required for Drosophila development under nutrient restriction (NR). We find two STIM-regulated peptides, Corazonin and short Neuropeptide F, to be required for NR larvae to complete development. Further, a set of secretory DLP (Dorso lateral peptidergic) neurons which co-express both peptides was identified. Partial loss of dSTIM caused peptide accumulation in the DLPs, and reduced systemic Corazonin signalling. Upon NR, larval development correlated with increased peptide levels in the DLPs, which failed to occur when dSTIM was reduced. Comparison of systemic and cellular phenotypes associated with reduced dSTIM, with other cellular perturbations, along with genetic rescue experiments, suggested that dSTIM primarily compromises neuroendocrine function by interfering with neuropeptide release. Under chronic stimulation, dSTIM also appears to regulate neuropeptide synthesis.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0219719}, author = {Wegener, Christian and Hasan, Gaiti} } @article {70230, title = {Evidence for a multi-level trophic organization of the human gut microbiome.}, journal = {PLoS Comput Biol}, volume = {15}, year = {2019}, month = {2019 Dec}, pages = {e1007524}, abstract = {

The human gut microbiome is a complex ecosystem, in which hundreds of microbial species and metabolites coexist, in part due to an extensive network of cross-feeding interactions. However, both the large-scale trophic organization of this ecosystem, and its effects on the underlying metabolic flow, remain unexplored. Here, using a simplified model, we provide quantitative support for a multi-level trophic organization of the human gut microbiome, where microbes consume and secrete metabolites in multiple iterative steps. Using a manually-curated set of metabolic interactions between microbes, our model suggests about four trophic levels, each characterized by a high level-to-level metabolic transfer of byproducts. It also quantitatively predicts the typical metabolic environment of the gut (fecal metabolome) in approximate agreement with the real data. To understand the consequences of this trophic organization, we quantify the metabolic flow and biomass distribution, and explore patterns of microbial and metabolic diversity in different levels. The hierarchical trophic organization suggested by our model can help mechanistically establish causal links between the abundances of microbes and metabolites in the human gut.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1007524}, author = {Wang, Tong and Goyal, Akshit and Dubinkina, Veronika and Maslov, Sergei} } @article {53170, title = {Evidence of filovirus and henipavirus in bats and bat harvesters, India}, journal = {International Journal of Infectious Diseases}, volume = {79}, year = {2019}, month = {02/2019}, pages = {60}, doi = {10.1016/j.ijid.2018.11.156}, author = {Br, A and Dovih, P and Ramakrishnan, U and Liang, E and Mendenhall, I and Wen Hong, D L and Smith, J G D} } @article {54874, title = {Evolthon: A community endeavor to evolve lab evolution.}, journal = {PLoS Biol}, volume = {17}, year = {2019}, month = {2019 Mar}, pages = {e3000182}, abstract = {

In experimental evolution, scientists evolve organisms in the lab, typically by challenging them to new environmental conditions. How best to evolve a desired trait? Should the challenge be applied abruptly, gradually, periodically, sporadically? Should one apply chemical mutagenesis, and do strains with high innate mutation rate evolve faster? What are ideal population sizes of evolving populations? There are endless strategies, beyond those that can be exposed by individual labs. We therefore arranged a community challenge, Evolthon, in which students and scientists from different labs were asked to evolve Escherichia coli or Saccharomyces cerevisiae for an abiotic stress-low temperature. About 30 participants from around the world explored diverse environmental and genetic regimes of evolution. After a period of evolution in each lab, all strains of each species were competed with one another. In yeast, the most successful strategies were those that used mating, underscoring the importance of sex in evolution. In bacteria, the fittest strain used a strategy based on exploration of different mutation rates. Different strategies displayed variable levels of performance and stability across additional challenges and conditions. This study therefore uncovers principles of effective experimental evolutionary regimens and might prove useful also for biotechnological developments of new strains and for understanding natural strategies in evolutionary arms races between species. Evolthon constitutes a model for community-based scientific exploration that encourages creativity and cooperation.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3000182}, author = {Kaminski Strauss, Sivan and Schirman, Dvir and Jona, Ghil and Brooks, Aaron N and Kunjapur, Aditya M and Nguyen Ba, Alex N and Flint, Alice and Solt, Andras and Mershin, Andreas and Dixit, Atray and Yona, Avihu H and Cs{\"o}rg{\H o}, B{\'a}lint and Busby, Bede Phillip and Hennig, Bianca P and P{\'a}l, Csaba and Schraivogel, Daniel and Schultz, Daniel and Wernick, David G and Agashe, Deepa and Levi, Dikla and Zabezhinsky, Dmitry and Russ, Dor and Sass, Ehud and Tamar, Einat and Herz, Elad and Levy, Emmanuel D and Church, George M and Yelin, Idan and Nachman, Iftach and Gerst, Jeffrey E and Georgeson, Joseph M and Adamala, Katarzyna P and Steinmetz, Lars M and R{\"u}bsam, Marc and Ralser, Markus and Klutstein, Michael and Desai, Michael M and Walunjkar, Nilima and Yin, Ning and Aharon Hefetz, Noa and Jakimo, Noah and Snitser, Olga and Adini, Omri and Kumar, Prashant and Soo Hoo Smith, Rachel and Zeidan, Razi and Hazan, Ronen and Rak, Roni and Kishony, Roy and Johnson, Shannon and Nouriel, Shira and Vonesch, Sibylle C and Foster, Simmie and Dagan, Tal and Wein, Tanita and Karydis, Thrasyvoulos and Wannier, Timothy M and Stiles, Timothy and Olin-Sandoval, Viridiana and Mueller, William F and Bar-On, Yinon M and Dahan, Orna and Pilpel, Yitzhak} } @article {45299, title = {Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes.}, journal = {Psychiatry Clin Neurosci}, volume = {73}, year = {2019}, month = {2018 Oct 27}, pages = {11-19}, abstract = {

AIM: Severe Mental Illnesses, such as bipolar disorder and schizophrenia, are highly heritable, and have a complex pattern of inheritance. Genome wide association studies detect a part of the heritability, which can be attributed to common genetic variation. Examination of rare variants with Next Generation Sequencing may add to the understanding of genetic architecture of SMIs.

METHODS: We analyzed 32 ill subjects from 8 multiplex families; and 33 healthy individuals by whole exome sequencing. Prioritized variants were selected by a 3-step filtering process, which included deleteriousness by 5 in silico algorithms; sharing within families by affected individuals, rarity in South Asian sample estimated using the Exome Aggregation Consortium data and complete absence of these variants in a control-individuals from the same gene pool.

RESULTS: We identified 42 rare, non-synonymous deleterious variants (~5 per pedigree) in this study. None of the variants were shared across families, indicating a {\textquoteright}private{\textquoteright} mutational profile. Twenty (47.6\%) of the variant harboring genes were previously reported to contribute to the risk of diverse neuropsychiatric syndromes; 9 (21.4\%) of which were of Mendelian inheritance. These included genes carrying novel deleterious variants such as GRM1 gene implicated in Spinocerebellar ataxia 44 and NIPBL gene implicated in Cornelia de Lange syndrome.

CONCLUSION: NGS approaches in family-based studies are useful to identify novel and rare variants in genes for complex disorders like SMI. The findings of the study suggest a potential phenotypic burden of rare variants in Mendelian disease genes, indicating pleiotropic effects in the etiology of SMI. This article is protected by copyright. All rights reserved.

}, issn = {1440-1819}, doi = {10.1111/pcn.12788}, author = {Ganesh, Suhas and Ahmed P, Husayn and Nadella, Ravi Kumar and More, Ravi Prabhakar and Sheshadri, Manasa and Viswanath, Biju and Rao, Mahendra and Jain, Sanjeev and Mukherjee, Odity} } @article {67825, title = {An expanded ND2 phylogeny of the brookii and prashadi groups with the description of three new Indian Hemidactylus Oken (Squamata: Gekkonidae).}, journal = {Zootaxa}, volume = {4619}, year = {2019}, month = {2019 Jun 20}, pages = {zootaxa.4619.3.2}, abstract = {

We present an expanded ND2 phylogeny of the brookii and prashadi groups of Indian Hemidactylus. While relationships within the clades are not well resolved, we recover many well supported subclades and a number of deeply divergent lineages within each clade. We use morphological data to describe three of these divergent lineages as new species; Hemidactylus kolliensis sp. nov., a member of the prashadi group from high elevation in the Kollimalai Massif in Tamil Nadu, Hemidactylus chikhaldaraensis sp. nov. and Hemidactylus sankariensis sp. nov., both members of the brookii group, are described from high elevation of the Satpuras in Maharashtra and low elevation of Tamil Nadu, respectively. The three new species exhibit \>15\% divergence for the ND2 gene from their phylogenetic sisters and differ in a number of morphological characters from all Indian congeners. The discovery of three more endemic Hemidactylus species from rocky habitats suggests that many more remain to be discovered across India.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4619.3.2}, author = {Agarwal, Ishan and Bauer, Aaron M and Giri, Varad B and Khandekar, Akshay} } @article {54875, title = {Exploring Endocytosis and Intracellular Trafficking of the Human Serotonin Receptor.}, journal = {Biochemistry}, year = {2019}, month = {2019 Mar 28}, abstract = {

G protein-coupled receptors (GPCRs) represent the largest class of receptors involved in signal transduction across cell membranes and are major drug targets in all clinical areas. Endocytosis of GPCRs offers a regulatory mechanism for sustaining their signaling within a stringent spatiotemporal regime. In this work, we explored agonist-induced endocytosis of the human serotonin receptor stably expressed in HEK-293 cells and the cellular machinery involved in receptor internalization and intracellular trafficking. The serotonin receptor is a popular GPCR implicated in neuropsychiatric disorders such as anxiety and depression and serves as an important drug target. In spite of its pharmacological relevance, its mechanism of endocytosis and intracellular trafficking is less understood. In this context, we have utilized a combination of robust population-based flow cytometric analysis and confocal microscopic imaging to address the path and fate of the serotonin receptor during endocytosis. Our results, utilizing inhibitors of specific endocytosis pathways and intracellular markers, show that the serotonin receptor undergoes endocytosis predominantly via the clathrin-mediated pathway and subsequently recycles to the plasma membrane via recycling endosomes. These results would enhance our understanding of molecular mechanisms of GPCR endocytosis and could offer novel insight into the underlying mechanism of antidepressants that act via the serotonergic pathway. In addition, our results could be relevant in understanding cell (or tissue)-specific GPCR endocytosis.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.9b00033}, author = {Kumar, G Aditya and Sarkar, Parijat and Jafurulla, Md and Singh, Shishu Pal and Srinivas, Gunda and Pande, Gopal and Chattopadhyay, Amitabha} } @article {51001, title = {Extended Flight Bouts Require Disinhibition from GABAergic Mushroom Body Neurons.}, journal = {Curr Biol}, volume = {29}, year = {2019}, month = {2019 Jan 21}, pages = {283-293.e5}, abstract = {

Insect flight is a complex behavior that requires the integration of multiple sensory inputs with flight motor output. Although previous genetic studies identified central brain monoaminergic neurons that modulate Drosophila flight, neuro-modulatory circuits underlying sustained flight bouts remain unexplored. Certain classes of dopaminergic and octopaminergic neurons that project to the mushroom body, a higher integrating center in the insect brain, are known to modify neuronal output based on contextual cues and thereby organismal behavior. This study focuses on how monoaminergic modulation of mushroom body GABAergic output neurons (MBONs) regulates the duration of flight bouts. Octopaminergic neurons in the sub-esophageal zone stimulate central dopaminergic neurons (protocerebral anterior medial, PAM) that project to GABAergic MBONs. Either inhibition of octopaminergic and dopaminergic neurons or activation of GABAergic MBONs reduces the duration of flight bouts. Moreover, activity in the PAM neurons inhibits the GABAergic MBONs. Our data suggest that disinhibition of the identified neural circuit very likely occurs after flight initiation and is required to maintain the "flight state" when searching for distant sites, possibly related to food sources, mating partners, or a suitable egg-laying site. VIDEO ABSTRACT.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2018.11.070}, author = {Manjila, Steffy B and Kuruvilla, Maria and Ferveur, Jean-Fran{\c c}ois and Sane, Sanjay P and Hasan, Gaiti} } @article {127107, title = {Extraction and Purification of Laccases from Rice Stems.}, journal = {Bio Protoc}, volume = {9}, year = {2019}, month = {2019 Apr 05}, pages = {e3208}, abstract = {

Laccases are found in cell walls of plants in very low amounts. This protocol provides an efficient method to purify laccases from rice stems. The method involves three steps: 1) Isolation of total protein from rice stems using buffers with high salt concentration to extract protein from cell walls; 2) Purification of laccases using concanavalin-A beads; and, 3) In-gel staining of laccases with 4-hydroxyindole. Concanavalin-A specifically binds to internal or non-reducing terminal α-D-mannosyl and α-D-glucosyl groups found in glycoproteins and glycolipids. Laccases being glycoproteins binds to concanavalin-A during purification process and eluted with mannose.

}, issn = {2331-8325}, doi = {10.21769/BioProtoc.3208}, author = {Swetha, Chenna and Shivaprasad, P V} } @article {67828, title = {Filovirus-reactive antibodies in humans and bats in Northeast India imply zoonotic spillover.}, journal = {PLoS Negl Trop Dis}, volume = {13}, year = {2019}, month = {2019 Oct}, pages = {e0007733}, abstract = {

Bats are reservoirs for several zoonotic pathogens, including filoviruses. Recent work highlights the diversity of bat borne filoviruses in Asia. High risk activities at the bat-human interface pose the threat of zoonotic virus transmission. We present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus surface glycoproteins by screening sera in a multiplexed serological assay. Antibodies reactive to two antigenically distinct filoviruses were detected in human sera and to three individual filoviruses in bats in remote Northeast India. Sera obtained from Eonycteris spelaea bats showed similar patterns of cross-reactivity as human samples, suggesting them as the species responsible for the spillover. In contrast, sera from Rousettus leschenaultii bats reacted to two different virus glycoproteins. Our results indicate circulation of several filoviruses in bats and the possibility for filovirus transmission from bats to humans.

}, issn = {1935-2735}, doi = {10.1371/journal.pntd.0007733}, author = {Dovih, Pilot and Laing, Eric D and Chen, Yihui and Low, Dolyce H W and Ansil, B R and Yang, Xinglou and Shi, Zhengli and Broder, Christopher C and Smith, Gavin J D and Linster, Martin and Ramakrishnan, Uma and Mendenhall, Ian H} } @article {50995, title = {A five-residue motif for the design of domain swapping in proteins.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 01 28}, pages = {452}, abstract = {

Domain swapping is the process by which identical monomeric proteins exchange structural elements to generate dimers/oligomers. Although engineered domain swapping is a compelling strategy for protein assembly, its application has been limited due to the lack of simple and reliable design approaches. Here, we demonstrate that the hydrophobic five-residue {\textquoteright}cystatin motif{\textquoteright} (QVVAG) from the domain-swapping protein Stefin B, when engineered into a solvent-exposed, tight surface loop between two β-strands prevents the loop from folding back upon itself, and drives domain swapping in non-domain-swapping proteins. High-resolution structural studies demonstrate that engineering the QVVAG stretch independently into various surface loops of four structurally distinct non-domain-swapping proteins enabled the design of different modes of domain swapping in these proteins, including single, double and open-ended domain swapping. These results suggest that the introduction of the QVVAG motif can be used as a mutational approach for engineering domain swapping in diverse β-hairpin proteins.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-08295-x}, author = {Nandwani, Neha and Surana, Parag and Negi, Hitendra and Mascarenhas, Nahren M and Udgaonkar, Jayant B and Das, Ranabir and Gosavi, Shachi} } @article {67830, title = {Flies land upside down on a ceiling using rapid visually mediated rotational maneuvers.}, journal = {Sci Adv}, volume = {5}, year = {2019}, month = {2019 Oct}, pages = {eaax1877}, abstract = {

Flies and other insects routinely land upside down on a ceiling. These inverted landing maneuvers are among the most remarkable aerobatic feats, yet the full range of these behaviors and their underlying sensorimotor processes remain largely unknown. Here, we report that successful inverted landing in flies involves a serial sequence of well-coordinated behavioral modules, consisting of an initial upward acceleration followed by rapid body rotation and leg extension, before terminating with a leg-assisted body swing pivoted around legs firmly attached to the ceiling. Statistical analyses suggest that rotational maneuvers are triggered when flies{\textquoteright} relative retinal expansion velocity reaches a threshold. Also, flies exhibit highly variable pitch and roll rates, which are strongly correlated to and likely mediated by multiple sensory cues. When flying with higher forward or lower upward velocities, flies decrease the pitch rate but increase the degree of leg-assisted swing, thereby leveraging the transfer of body linear momentum.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aax1877}, author = {Liu, Pan and Sane, Sanjay P and Mongeau, Jean-Michel and Zhao, Jianguo and Cheng, Bo} } @article {99943, title = {Fold combinations in multi-domain proteins.}, journal = {Bioinformation}, volume = {15}, year = {2019}, month = {2019}, pages = {342-350}, abstract = {

Domain-domain interactions in multi-domain proteins play an important role in the combined function of individual domains for the overall biological activity of the protein. The functions of the tethered domains are often coupled and hence, limited numbers of domain architectures with defined folds are known in nature. Therefore, it is of interest to document the available fold-fold combinations and their preference in multi-domain proteins. Hence, we analyzed all multi-domain proteins with known structures in the protein databank and observed that only about 860 fold-fold combinations are present among them. Analyses of multi-domain proteins represented in sequence database result in recognition of 29,860 fold-fold combinations and it accounts for only 2.8\% of the theoretically possible 1,036,080 (1439C2) fold-fold combinations. The observed preference for fold-fold combinations in multi-domain proteins is interesting in the context of multiple functions through structural adaptation by gene fusion.

}, issn = {0973-2063}, doi = {10.6026/97320630015342}, author = {Naveenkumar, Nagarajan and Kumar, Gayatri and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy and Vishwanath, Sneha} } @article {59728, title = {Formal structures of mentorship in universities and research institutions will benefit both science and scientists}, journal = {Current Science}, volume = {116}, year = {2019}, month = {05/2019}, pages = {1615-1616}, url = {https://www.currentscience.ac.in/Volumes/116/10/1615.pdf}, author = {Hasan, Gaiti} } @article {66853, title = {From a syncytium to mononucleate cells and back: Yki and JNK in symphony.}, journal = {J Cell Biol}, year = {2019}, month = {2019 Oct 25}, abstract = {

Alary muscle syncytia in larvae undergo a remarkable process of dedifferentiation into single cells that then fuse to become ventral longitudinal muscle in the adult. In this issue, Schaub et al. (2019. https://doi.org/10.1083/jcb.201905048) identify the Hippo and JNK signaling pathways as key regulators of this process of developmental remodeling of cell fate.

}, issn = {1540-8140}, doi = {10.1083/jcb.201910025}, author = {Chaturvedi, Dhananjay and VijayRaghavan, K} } @article {64318, title = {Frost maintains forests and grasslands as alternate states in a montane tropical forest{\textendash}grassland mosaic; but alien tree invasion and warming can disrupt this balance}, journal = {JOURNAL OF ECOLOGY}, year = {2019}, month = {07/2019}, doi = {10.1111/1365-2745.13239}, author = {Joshi, Atul A and Ratnam, Jayashree and Sankaran, Mahesh} } @article {67832, title = {Frustration and fidelity in influenza genome assembly.}, journal = {J R Soc Interface}, volume = {16}, year = {2019}, month = {2019 Nov 29}, pages = {20190411}, abstract = {

The genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments. Cell-biological studies suggest that genome assembly is mediated by specific reversible and irreversible interactions between the RNA segments and their associated proteins. However, the precise inter-segment interaction network remains unresolved. Here, we computationally predict that tree-like irreversible interaction networks guarantee high-fidelity genome assembly, while cyclic interaction networks lead to futile or frustrated off-pathway products. We test our prediction against multiple experimental datasets. We find that tree-like networks capture the nearest-neighbour statistics of RNA segments in packaged virions, as observed by electron tomography. Just eight tree-like networks (of a possible 262 144) optimally capture both the nearest-neighbour data and independently measured RNA-RNA binding and co-localization propensities. These eight do not include the previously proposed hub-and-spoke and linear networks. Rather, each predicted network combines hub-like and linear features, consistent with evolutionary models of interaction gain and loss.

}, issn = {1742-5662}, doi = {10.1098/rsif.2019.0411}, author = {Farheen, Nida and Thattai, Mukund} } @article {59715, title = {A Functional Agonist of Insect Olfactory Receptors: Behavior, Physiology and Structure.}, journal = {Front Cell Neurosci}, volume = {13}, year = {2019}, month = {2019}, pages = {134}, abstract = {

Chemical signaling is ubiquitous and employs a variety of receptor types to detect the cacophony of molecules relevant for each living organism. Insects, our most diverse taxon, have evolved unique olfactory receptors with as little as 10\% sequence identity between receptor types. We have identified a promiscuous volatile, 2-methyltetrahydro-3-furanone (coffee furanone), that elicits chemosensory and behavioral activity across multiple insect orders and receptors. and physiology showed that coffee furanone was detected by roughly 80\% of the recorded neurons expressing the insect-specific olfactory receptor complex in the antenna of , at concentrations similar to other known, and less promiscuous, ligands. Neurons expressing specialized receptors, other chemoreceptor types, or mutants lacking the complex entirely did not respond to this compound. This indicates that coffee furanone is a promiscuous ligand for the insect olfactory receptor complex itself and did not induce non-specific cellular responses. In addition, we present homology modeling and docking studies with selected olfactory receptors that suggest conserved interaction regions for both coffee furanone and known ligands. Apart from its physiological activity, this known food additive elicits a behavioral response for several insects, including mosquitoes, flies, and cockroaches. A broad-scale behaviorally active molecule non-toxic to humans thus has significant implications for health and agriculture. Coffee furanone serves as a unique tool to unlock molecular, physiological, and behavioral relationships across this diverse receptor family and animal taxa.

}, issn = {1662-5102}, doi = {10.3389/fncel.2019.00134}, author = {Batra, Srishti and Corcoran, Jacob and Zhang, Dan-Dan and Pal, Pramit and K P, Umesh and Kulkarni, Renuka and L{\"o}fstedt, Christer and Sowdhamini, Ramanathan and Olsson, Shannon B} } @article {51226, title = {Functional analysis of the biochemical activity of mammalian phosphatidylinositol 5 phosphate 4-kinase enzymes.}, journal = {Biosci Rep}, year = {2019}, month = {2019 Feb 04}, abstract = {

Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) are enzymes that catalyse the phosphorylation of PI5P to generate PI(4,5)P Mammalian genomes contain three genes, PIP4K2A, 2B and 2C and murine knockouts for these suggest important physiological roles The proteins encoded by PIP4K2A, 2B and 2C show widely varying specific activity ; PIP4K2A is highly active and PIP4K2C 2000 times less active and the relationship between this biochemical activity and function is unknown. By contrast the genome encodes a single PIP4K (dPIP4K) that shows high specific activity and loss of this enzyme results in reduced salivary gland cell size We find that the kinase activity of dPIP4K is essential for normal salivary gland cell size Despite their highly divergent specific activity, we find that all three mammalian PIP4K isoforms are able to enhance salivary gland cell size in implying a lack of correlation between activity measurement and function. Further, the kinase activity of PIP4K2C, reported to be almost inactive is required for function. Our findings suggest the existence of unidentified factors that regulate PIP4K enzyme activity .

}, issn = {1573-4935}, doi = {10.1042/BSR20182210}, author = {Mathre, Swarna and Reddy, Balasankara and Ramya, Visvanathan and Krishnan, Harini and Ghosh, Avishek and Raghu, Padinjat} } @article {53619, title = {Functional Traits of Trees From Dry Deciduous {\textquotedblleft}Forests{\textquotedblright} of Southern India Suggest Seasonal Drought and Fire Are Important Drivers}, journal = {Front. Ecol. Evol.}, year = {2019}, month = {01/2019}, abstract = {

Two dominant biomes that occur across the southern Indian peninsula are dry deciduous {\textquotedblleft}forests{\textquotedblright} and evergreen forests, with the former occurring in drier regions and the latter in wetter regions, sometimes in close proximity to each other. Here we compare stem and leaf traits of trees from multiple sites across these biomes to show that dry deciduous {\textquotedblleft}forest{\textquotedblright} species have, on average, lower height: diameter ratios, lower specific leaf areas, higher wood densities and higher relative bark thickness, than evergreen forest species. These traits are diagnostic of these dry deciduous {\textquotedblleft}forests{\textquotedblright} as open, well-lit, drought-, and fire-prone habitats where trees are conservative in their growth strategies and invest heavily in protective bark tissue. These tree traits together with the occurrence of a C4 grass-dominated understory, diverse mammalian grazers, and frequent fires indicate that large tracts of dry deciduous {\textquotedblleft}forests{\textquotedblright} of southern India are more accurately classified as mesic deciduous {\textquotedblleft}savannas.{\textquotedblright}

}, doi = {10.3389/fevo.2019.00008}, author = {Ratnam, Jayashree and Chengappa, SK and Machado, Siddarth and Nataraj, N and Osuri, Anand M and Sankaran, Mahesh} } @article {55796, title = {GenDiS database update with improved approach and features to recognize homologous sequences of protein domain superfamilies.}, journal = {Database (Oxford)}, volume = {2019}, year = {2019}, month = {2019 01 01}, abstract = {

Since proteins evolve by divergent evolution, proteins with distant homology to each other may or may not bear similar functions. Improved computational approaches are required to recognize distant homologues that are functionally similar. One of the methods of assigning function to sequences is to use profiles derived from sequences of known structure. We describe an update of the Genomic Distribution of protein structural domain Superfamilies (GenDiS) database, namely GenDiS+, which provides a projection of SCOP superfamily members on the sequence space (NR database, NCBI). The sequences are validated using structure-based sequence alignment profiles and domain and full-length sequence alignments. GenDiS+ is a {\textquoteleft}tour de force{\textquoteright} for detecting homologues within around 160 000 taxonomic identifiers, starting from nearly 11 000 domains of known structure. Features, like full-sequence alignment and phylogeny, domain sequence alignment and phylogeny, list of associated structural and sequence domains with strength of interactions, links to databases like Pfam, UniProt and ModBase and list of sequences with a PDB structure, are provided.

}, issn = {1758-0463}, doi = {10.1093/database/baz042}, author = {Iyer, Meenakshi S and Bhargava, Kartik and Pavalam, Murugavel and Sowdhamini, Ramanathan} } @article {57785, title = {Genetic architecture and sex-specific selection govern modular, male-biased evolution of .}, journal = {Sci Adv}, volume = {5}, year = {2019}, month = {2019 May}, pages = {eaau3753}, abstract = {

regulates early embryonic sex differentiation in holometabolous insects, along with the development of species-, sex-, and morph-specific adaptations during pupal stages. How does a highly conserved gene with a critical developmental role also remain functionally dynamic enough to gain ecologically important adaptations that are divergent in sister species? We analyzed patterns of exon-level molecular evolution and protein structural homology of from 145 species of four insect orders representing 350 million years of divergence. This analysis revealed that evolution of was governed by a modular architecture: Functional domains and female-specific regions were highly conserved, whereas male-specific sequences and protein structures evolved up to thousand-fold faster, with sites under pervasive and/or episodic positive selection. This pattern of sex bias was reversed in Hymenoptera. Thus, highly conserved yet dynamic master regulators such as may partition specific conserved and novel functions in different genic modules at deep evolutionary time scales.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aau3753}, author = {Baral, Saurav and Arumugam, Gandhimathi and Deshmukh, Riddhi and Kunte, Krushnamegh} } @article {50994, title = {Genome-Wide Analysis of Domain-Swap Predicted Products in the Genome of Anti-Stress Medicinal Plant: .}, journal = {Bioinform Biol Insights}, volume = {13}, year = {2019}, month = {2019}, pages = {1177932218821362}, abstract = {

Computational approaches to high-throughput data are gaining importance because of explosion of sequences in the post-genomic era. This explosion of sequence data creates a huge gap among the domains of sequence structure and function, since the experimental techniques to determine the structure and function are very expensive, time taking, and laborious in nature. Therefore, there is an urgent need to emphasize on the development of computational approaches in the field of biological systems. Engagement of proteins in quaternary arrangements, such as domain swapping, might be relevant for higher compatibility of such genes at stress conditions. In this study, the capacity to engage in domain swapping was predicted from mere sequence information in the whole genome of holy Basil (), which is well known to be an anti-stress agent. Approximately, one-fourth of the proteins of are predicted to undergo three-dimensional (3D)-domain swapping. Furthermore, function annotation was carried out on all the predicted domain-swap sequences from the and for their distribution in different Pfam protein families and gene ontology (GO) terms. These domain-swapped protein sequences are associated with many Pfam protein families with a wide range of GO annotation terms. A comparative analysis of domain-swap-predicted sequences in with gene products in reveals that around 26\% (2522 sequences) are close homologues across the 2 genomes. Functional annotation of predicted domain-swapped sequences infers that predicted domain-swap sequences are involved in diverse molecular functions, such as in gene regulation of abiotic stress conditions and adaptation to different environmental niches. Finally, the positively predicted sequences of and were also examined for their presence in stress regulome, as recorded in our STIFDB database, to check the involvement of these proteins in different abiotic stresses.

}, issn = {1177-9322}, doi = {10.1177/1177932218821362}, author = {Upadhyay, Atul Kumar and Sowdhamini, Ramanathan} } @article {56126, title = {Genome-Wide Search for Tyrosine Phosphatases in the Human Genome Through Computational Approaches Leads to the Discovery of Few New Domain Architectures.}, journal = {Evol Bioinform Online}, volume = {15}, year = {2019}, month = {2019}, pages = {1176934319840289}, abstract = {

Reversible phosphorylation maintained by protein kinases and phosphatases is an integral part of intracellular signalling, and phosphorylation on tyrosine is extensively utilised in higher eukaryotes. Tyrosine phosphatases are enzymes that not only scavenge phosphotyrosine but are also involved in wide range of signalling pathways. As a result, mutations in these enzymes have been implicated in the pathogenesis of several diseases like cancer, autoimmune disorders, and muscle-related diseases. The genes that harbour phosphatase domain also display diversity in co-existing domains suggesting the recruitment of the catalytic machinery in diverse pathways. We have examined the current draft of the human genome, using a combination of 3 sequence search methods and validations, and identified 101 genes encoding tyrosine phosphatase-containing gene products, agreeing with previous reports. Such gene products adopt 37 unique domain architectures (DAs), including few new ones and harbouring few co-existing domains that have not been reported before. This semi-automated computational approach for detection of gene products belonging to a particular superfamily can now be easily applied at whole genome level on other mammalian genomes and for other protein domains as well.

}, issn = {1176-9343}, doi = {10.1177/1176934319840289}, author = {Bhattacharyya, Teerna and Sowdhamini, Ramanathan} } @article {60613, title = {Geographical and host species barriers differentially affect generalist and specialist parasite community structure in a tropical sky-island archipelago.}, journal = {Proc Biol Sci}, volume = {286}, year = {2019}, month = {2019 Jun 12}, pages = {20190439}, abstract = {

Understanding why some parasites emerge in novel host communities while others do not has broad implications for human and wildlife health. In the case of haemosporidian blood parasites, epidemic wild bird mortalities on oceanic islands have been linked to Plasmodium spp., but not genera like Haemoproteus. Indeed, Haemoproteus is absent from many oceanic islands. By contrast, birds on continental islands share long coevolutionary histories with both Plasmodium and Haemoproteus, and are thus ideal model systems to elucidate eco-evolutionary endpoints associated with these parasites in oceanic islands. Here, we examine eco-evolutionary dynamics of avian haemosporidian in the Shola sky-island archipelago of the Western Ghats, India. Our analyses reveal that compared to Plasmodium, Haemoproteus lineages were highly host-specific and diversified via co-speciation with their hosts. We show that community structure of host-generalist Plasmodium was primarily driven by geographical factors (e.g. biogeographic barriers), while that of host-specialist Haemoproteus was driven by host species barriers (e.g. phylogenetic distance). Consequently, a few host species can harbour a high diversity of Plasmodium lineages which, in turn, are capable of infecting multiple host species. These two mechanisms can act in concert to increase the risk of introduction, establishment, and emergence of novel Plasmodium lineages in island systems.

}, issn = {1471-2954}, doi = {10.1098/rspb.2019.0439}, author = {Gupta, Pooja and Vishnudas, C K and Ramakrishnan, Uma and Robin, V V and Dharmarajan, Guha} } @article {55790, title = {Go-Kit: A Tool To Enable Energy Landscape Exploration of Proteins.}, journal = {J Chem Inf Model}, year = {2019}, month = {2019 Apr 12}, abstract = {

Coarse-grained Go̅-like models, based on the principle of minimal frustration, provide valuable insight into fundamental questions in the field of protein folding and dynamics. In conjunction with commonly used molecular dynamics (MD) simulations, energy landscape exploration methods like discrete path sampling (DPS) with Go̅-like models can provide quantitative details of the thermodynamics and kinetics of proteins. Here we present Go-kit, a software that facilitates the setup of MD and DPS simulations of several flavors of Go̅-like models. Go-kit is designed for use with MD (GROMACS) and DPS (PATHSAMPLE) simulation engines that are open source. The Go-kit code is written in python2.7 and is also open source. A case study for the ribosomal protein S6 is discussed to illustrate the utility of the software, which is available at https://github.com/gokit1/gokit .

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.9b00007}, author = {Neelamraju, Sridhar and Wales, David J and Gosavi, Shachi} } @article {64331, title = {Heinrich Reichert (1949-2019).}, journal = {Development}, volume = {146}, year = {2019}, month = {2019 Aug 19}, abstract = {

Heinrich Reichert, Professor Emeritus at the University of Basel, Switzerland, passed away on the 13th of June 2019 after a prolonged illness. Heinrich described himself as {\textquoteright}a hedonist when it came to science{\textquoteright} because he said it gave him great pleasure. It was this quality that made working with Heinrich thrilling and deeply fulfilling. Heinrich{\textquoteright}s long and versatile career spanned the breadth of neuroscience - from development, to evolution and behaviour. In his passing we have lost not just an astute scientist, but also an impassioned educator and an adventurer of science.

}, issn = {1477-9129}, doi = {10.1242/dev.183517}, author = {Sen, Sonia and VijayRaghavan, K} } @article {53171, title = {The high efficacy of muscarinic M4 receptor in D1 medium spiny neurons reverses striatal hyperdopaminergia.}, journal = {Neuropharmacology}, volume = {146}, year = {2019}, month = {2019 Mar 01}, pages = {74-83}, abstract = {

The opposing action of dopamine and acetylcholine has long been known to play an important role in basal ganglia physiology. However, the quantitative analysis of dopamine and acetylcholine signal interaction has been difficult to perform in the native context because the striatum comprises mainly two subtypes of medium-sized spiny neurons (MSNs) on which these neuromodulators exert different actions. We used biosensor imaging in live brain slices of dorsomedial striatum to monitor changes in intracellular cAMP at the level of individual MSNs. We observed that the muscarinic agonist oxotremorine decreases cAMP selectively in the MSN subpopulation that also expresses D dopamine receptors, an action mediated by the M muscarinic receptor. This receptor has a high efficacy on cAMP signaling and can shut down the positive cAMP response induced by dopamine, at acetylcholine concentrations which are consistent with physiological levels. This supports our prediction based on theoretical modeling that acetylcholine could exert a tonic inhibition on striatal cAMP signaling, thus supporting the possibility that a pause in acetylcholine release is required for phasic dopamine to transduce a cAMP signal in D1 MSNs. In vivo experiments with acetylcholinesterase inhibitors donepezil and tacrine, as well as with the positive allosteric modulators of M receptor VU0152100 and VU0010010 show that this effect is sufficient to reverse the increased locomotor activity of DAT-knockout mice. This suggests that M receptors could be a novel therapeutic target to treat hyperactivity disorders.

}, issn = {1873-7064}, doi = {10.1016/j.neuropharm.2018.11.029}, author = {Nair, Anu G and Castro, Liliana R V and El Khoury, Marianne and Gorgievski, Victor and Giros, Bruno and Tzavara, Eleni T and Hellgren-Kotaleski, Jeanette and Vincent, Pierre} } @article {59739, title = {The hills are alive with geckos! A radiation of a dozen species on sky islands across peninsular India (Squamata: Gekkonidae, Hemiphyllodactylus) with the description of three new species}, journal = {Organisms Diversity \& Evolution}, volume = {19}, year = {2019}, month = {06/2019}, pages = {341{\textendash}361}, abstract = {

Sky Islands are high-elevation environments that are separated by warmer, low elevations, forming natural patches of unique montane habitat that often persist through changing climates. Peninsular India was ancestrally forested and has gradually become more arid since at least the Oligocene, and open landscapes have dominated since the middle-late Miocene. Mesic forests today are largely restricted to coastal mountains and some other montane habitats. A mitochondrial phylogeny and fossil-calibrated timetree of Indian Hemiphyllodactylus reveal an Indochinese origin and an endemic radiation with 12 species-level lineages, where a single species was known, that diversified in the Oligocene-Miocene across montane forest habitats in the Eastern Ghats and south India. The phylogeny also suggests the discontinuous Eastern Ghats mountain range encompasses two distinct biogeographic entities: north and south of the Pennar/Krishna-Godavari River basins. This study\ highlights the deep history of the region and the importance of montane habitats as islands of unique biodiversity that have persisted through millions of years of changing climates. We describe three new species: Hemiphyllodactylus arakuensis sp. nov., H. jnana sp. nov. and H. kolliensis sp. nov. from montane habitats above 1000\ m. The montane habitats of these species are emerging hotspots of reptile endemism, and this study emphasizes the need for systematic biodiversity inventory across India to uncover basic patterns of diversity and distribution.

}, doi = {10.1007/s13127-019-00392-5}, author = {Agarwal, Ishan and Khandekar, A and Giri, Varad B. and Ramakrishnan, Uma and Karanth, Praveen} } @article {59721, title = {Honey bees flexibly use two navigational memories when updating dance distance information.}, journal = {J Exp Biol}, volume = {222}, year = {2019}, month = {2019 Jun 13}, abstract = {

Honey bees can communicate navigational information which makes them unique amongst all prominent insect navigators. Returning foragers recruit nest mates to a food source by communicating flight distance and direction using a small scale walking pattern: the waggle dance. It is still unclear how bees transpose flight information to generate corresponding dance information. In single feeder shift experiments, we monitored for the first time how individual bees update dance duration after a shift of feeder distance. Interestingly, the majority of bees (86\%) needed two or more foraging trips to update dance duration. This finding demonstrates that transposing flight navigation information to dance information is not a reflexive behavior. Furthermore, many bees showed intermediate dance durations during the update process, indicating that honey bees highly likely use two memories: (i) a recently acquired navigation experience and (ii) a previously stored flight experience. Double-shift experiments, in which the feeder was moved forward and backward, created an experimental condition in which honey bee foragers did not update dance duration; suggesting the involvement of more complex memory processes. Our behavioral paradigm allows the dissociation of foraging and dance activity and opens the possibility of studying the molecular and neural processes underlying the waggle dance behavior.

}, issn = {1477-9145}, doi = {10.1242/jeb.195099}, author = {Chatterjee, Arumoy and George, Ebi A and M V, Prabhudev and Basu, Pallab and Brockmann, Axel} } @article {68513, title = {Host dietary specialization and neutral assembly shape gut bacterial communities of wild dragonflies.}, journal = {PeerJ}, volume = {7}, year = {2019}, month = {2019}, pages = {e8058}, abstract = {

Host-associated gut microbiota can have significant impacts on host ecology and evolution and are often host-specific. Multiple factors can contribute to such host-specificity: (1) host dietary specialization passively determining microbial colonization, (2) hosts selecting for specific diet-acquired microbiota, or (3) a combination of both. The latter possibilities indicate a functional association and should produce stable microbiota. We tested these alternatives by analyzing the gut bacterial communities of six species of wild adult dragonfly populations collected across several geographic locations. The bacterial community composition was predominantly explained by sampling location, and only secondarily by host identity. To distinguish the role of host dietary specialization and host-imposed selection, we identified prey in the guts of three dragonfly species. Surprisingly, the dragonflies-considered to be generalist predators-consumed distinct prey; and the prey diversity was strongly correlated with the gut bacterial profile. Such host dietary specialization and spatial variation in bacterial communities suggested passive rather than selective underlying processes. Indeed, the abundance and distribution of 72\% of bacterial taxa were consistent with neutral community assembly; and fluorescent in situ hybridization revealed that bacteria only rarely colonized the gut lining. Our results contradict the expectation that host-imposed selection shapes the gut microbiota of most insects, and highlight the importance of joint analyses of diet and gut microbiota of natural host populations.

}, issn = {2167-8359}, doi = {10.7717/peerj.8058}, author = {Deb, Rittik and Nair, Ashwin and Agashe, Deepa} } @article {67837, title = {How contraction has shaped evolution.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Nov 14}, abstract = {

Two unicellular relatives of animals reveal that coordinated contractions of groups of cells using actomyosin predated animal multicellularity during evolution.

}, issn = {2050-084X}, doi = {10.7554/eLife.52805}, author = {Thattai, Mukund} } @article {60329, title = {How Do Trait-Mediated Non-lethal Effects of Predation Affect Population-Level Performance of Mosquitoes?}, journal = {Front Ecol Evol}, volume = {7}, year = {2019}, month = {2019 Feb}, abstract = {

Non-lethal, trait-mediated effects of predation impact prey behavior and life-history traits. Studying how these effects in turn influence prey demography is crucial to understand prey life-history evolution. Mosquitoes are important vectors that claim several million lives every year worldwide by transmitting a range of pathogens. Several ecological factors affect life-history traits of both larval and adult mosquitoes, creating effects that cascade to population-level consequences. Few studies have comprehensively explored the non-lethal effects of predation and its interactions with resources and competition on larval, adult, and population traits of mosquitoes. Understanding these interactions is important because the effects of predation are hypothesized to rescue prey populations from the effects of density-dependence resulting from larval competition. larvae reared at two different larval densities and subjected to three non-lethal predator treatments were monitored for survival, development time, and adult size through the larval stages to adult eclosion, and adult females were monitored for survival and reproduction through their first gonotrophic cycle. Intraspecific competition increased larval development time, yielded small-bodied adults, and reduced fecundity in individuals exposed to predatory chemical cues as larvae. Exposure to cues from a living predator affected both body size and latency to blood feed in females. Analysis of life-table traits revealed significant effects of competition on net reproductive rate () of mosquitoes. The interaction between competition and predator treatments significantly affected the cohort rate of increase () and the index of performance ({\textquoteright}). The index of performance, which estimates rate of population change based on the size-fecundity relationship, was significantly and positively correlated with , but overestimated slightly. Lack of significant effect of predator treatments and larval density on cohort generation time () further suggests that the observed effects of treatments on and were largely a consequence of the effects on . Also, the significant effects of treatment combinations on larval development time, adult body size and fecundity were ultimately manifested as effects on life-table traits estimated from adult survival and reproduction.

}, issn = {2296-701X}, doi = {10.3389/fevo.2019.00025}, author = {Chandrasegaran, Karthikeyan and Juliano, Steven A} } @article {71094, title = {Human footprint differentially impacts genetic connectivity of four wide-ranging mammals in a fragmented landscape}, journal = {Diversity and Distribution}, year = {2019}, month = {12/2019}, abstract = {

Aim

Maintaining connectivity is critical for long-term persistence of wild carnivores in landscapes fragmented due to anthropogenic activity. We examined spatial genetic structure and the impact of landscape features on genetic structure in four widespread species{\textemdash}jungle cat (Felis chaus), leopard (Panthera pardus), sloth bear (Melursus ursinus) and tiger (Panthera tigris).

Location

Our study was carried out in the central Indian landscape, a stronghold in terms of distribution and abundance of large mammals. The landscape comprises fragmented forests embedded in a heterogeneous matrix of multiple land use types.

Methods

Microsatellite data from non-invasively sampled individuals (90 jungle cats, 82 leopards, 104 sloth bears and 117 tigers) were used to investigate genetic differentiation. Impact of landscape features on genetic structure was inferred using a multimodel landscape resistance optimization approach.

Results

All four study species revealed significant isolation by distance (IBD). The correlation between genetic and geographic distance was significant only over a short distance for jungle cat, followed by longer distances for sloth bear, leopard and tiger. Overall, human footprint had a high negative impact on gene flow in tigers, followed by leopards, sloth bears and the least on jungle cats. Individual landscape variables{\textemdash}land use, human population density, density of linear features and roads{\textemdash}impacted the study species differently. Although land use was found to be an important variable explaining genetic structure for all four species, the amount of variation explained, and the optimum spatial resolution and the resistance values of different land use classes varied.

Main conclusions

As expected from theory, but rarely demonstrated using empirical data, the pattern of spatial autocorrelation of genetic variation scaled with dispersal ability and density of the study species. Landscape genetic analyses revealed species-specific impact of landscape features and provided insights into interactions between species biology and landscape structure. Our results emphasize the need for incorporating functional connectivity data from multiple species for landscape-level conservation planning.

}, doi = {10.1111/ddi.13022}, author = {Thatte, P and Chandramouli, A and Tyagi, A and Patel, K and Baro, B and Chhattani, H and Ramakrishnan, U} } @article {66844, title = {Identification and functional characterization of two novel mutations in KCNJ10 and PI4KB in SeSAME syndrome without electrolyte imbalance.}, journal = {Hum Genomics}, volume = {13}, year = {2019}, month = {2019 10 22}, pages = {53}, abstract = {

BACKGROUND: Dysfunction in inwardly rectifying potassium channel Kir4.1 has been implicated in SeSAME syndrome, an autosomal-recessive (AR), rare, multi-systemic disorder. However, not all neurological, intellectual disability, and comorbid phenotypes in SeSAME syndrome can be mechanistically linked solely to Kir4.1 dysfunction.

METHODS: We therefore performed whole-exome sequencing and identified additional genetic risk-elements that might exert causative effects either alone or in concert with Kir4.1 in a family diagnosed with SeSAME syndrome.

RESULTS: Two variant prioritization pipelines based on AR inheritance and runs of homozygosity (ROH), identified two novel homozygous variants in KCNJ10 and PI4KB and five rare homozygous variants in PVRL4, RORC, FLG2, FCRL1, NIT1 and one common homozygous variant in HSPA6 segregating in all four patients. The novel mutation in KCNJ10 resides in the cytoplasmic domain of Kir4.1, a seat of phosphatidylinositol bisphosphate (PIP2) binding. The mutation altered the subcellular localization and stability of Kir4.1 in patient-specific lymphoblastoid cells (LCLs) compared to parental controls. Barium-sensitive endogenous K currents in patient-specific LCLs using whole-cell patch-clamp electrophysiology revealed membrane depolarization and defects in inward K ion conductance across the membrane, thereby suggesting a loss-of-function effect of KCNJ10 variant.

CONCLUSION: Altogether, our findings implicate the role of new genes in SeSAME syndrome without electrolyte imbalance and thereby speculate the regulation of Kir4.1 channel activity by PIP2 and integrin-mediated adhesion signaling mechanisms.

}, issn = {1479-7364}, doi = {10.1186/s40246-019-0236-0}, author = {Nadella, Ravi K and Chellappa, Anirudh and Subramaniam, Anand G and More, Ravi Prabhakar and Shetty, Srividya and Prakash, Suriya and Ratna, Nikhil and Vandana, V P and Purushottam, Meera and Saini, Jitender and Viswanath, Biju and Bindu, P S and Nagappa, Madhu and Mehta, Bhupesh and Jain, Sanjeev and Kannan, Ramakrishnan} } @article {62779, title = {Image reconstruction from undersampled confocal microscopy data using multiresolution based maximum entropy regularization}, journal = {Journal of Instrumentation}, volume = {14}, year = {2019}, month = {07/2019}, abstract = {

We consider the problem of reconstructing 2D images from randomly under-sampled confocal microscopy samples. The well known and widely celebrated total variation regularization, which is the

l1 norm of derivatives, turns out to be unsuitable for this problem; it is unable to handle both noise and under-sampling together. This issue is linked with the notion of phase transition phenomenon observed in compressive sensing research, which is essentially the break-down of total variation methods, when sampling density gets lower than certain threshold. The severity of this breakdown is determined by the so-called mutual incoherence between the derivative operators and measurement operator. In our problem, the mutual incoherence is low, and hence the total variation regularization gives serious artifacts in the presence of noise even when the sampling density is not very low. There has been very few attempts in developing regularization methods that perform better than total variation regularization for this problem. We develop a multi-resolution based regularization method that is adaptive to image structure. In our approach, the desired reconstruction is formulated as a series of coarse-to-fine multi-resolution reconstructions; for reconstruction at each level, the regularization is constructed to be adaptive to the image structure, where the information for adaption is obtained from the reconstruction obtained at coarser resolution level. This adaptation is achieved by using maximum entropy principle, where the required adaptive regularization is determined as the maximizer of entropy subject to the information extracted from the coarse reconstruction as constraints. We also utilize the directionally adaptive second order derivatives for constructing the regularization with directions guided by the given coarse reconstruction, which leads to an improved suppression of artifacts. We demonstrate the superiority of the proposed regularization method over existing ones using several reconstruction examples.

}, doi = {10.1088/1748-0221/14/07/P07015}, author = {Francis, B and Mathew, Manoj and Arigovindan, M} } @article {45301, title = {Immediate early genes in social insects: a tool to identify brain regions involved in complex behaviors and molecular processes underlying neuroplasticity.}, journal = {Cell Mol Life Sci}, volume = {76}, year = {2019}, month = {2018 Oct 22}, pages = {637-651}, abstract = {

Social insects show complex behaviors and master cognitive tasks. The underlying neuronal mechanisms, however, are in most cases only poorly understood due to challenges in monitoring brain activity in freely moving animals. Immediate early genes (IEGs) that get rapidly and transiently expressed following neuronal stimulation provide a powerful tool for detecting behavior-related neuronal activity in vertebrates. In social insects, like honey bees, and in insects in general, this approach is not yet routinely established, even though these genes are highly conserved. First studies revealed a vast potential of using IEGs as neuronal activity markers to analyze the localization, function, and plasticity of neuronal circuits underlying complex social behaviors. We summarize the current knowledge on IEGs in social insects and provide ideas for future research directions.

}, issn = {1420-9071}, doi = {10.1007/s00018-018-2948-z}, author = {Sommerlandt, Frank M J and Brockmann, Axel and R{\"o}ssler, Wolfgang and Spaethe, Johannes} } @inbook {79737, title = {Immunomodulatory and Therapeutic Potential of Marine Flora Products in the Treatment of Cancer}, booktitle = {Bioactive Natural Products for the Management of Cancer: from Bench to Bedside }, year = {2019}, pages = {139-166}, publisher = {Springer}, organization = {Springer}, chapter = {7}, abstract = {

Marine floras, constituting over 90\% of the oceanic biomass, are rich sources of potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. They act as potential sources of drugs with various pharmacological properties (such as antioxidant, anti-inflammatory, antibiotic, immunostimulatory, and anticancer). Although human history depicts the use of marine floras as medicine and nutrient supplement, the search for novel pharmaceutical compounds has mostly been limited to terrestrial floras. Marine floras are taxonomically diverse, largely productive, biologically active, and chemically unique, thereby offering great scope for discovery of new anticancer drugs. The mode of action of marine flora products is through activation of macrophages, induction of apoptosis, and prevention of oxidative damage of DNA, thereby controlling carcinogenesis. This chapter focuses on the immunomodulatory and therapeutic properties of marine flora-derived products in the context of increasing cancer incidences and demand for cheaper, safer, and potent anticancer drugs. It highlights the excellent therapeutic potential of the known marine flora-derived anticancer compounds, thereby encouraging researchers to actively participate in the marine natural product drug discovery for treatment and prevention of cancer.

}, isbn = {978-981-13-7606-1}, doi = {10.1007/978-981-13-7607-8_7}, author = {Singh, A and Krishna, Sudhir} } @article {67835, title = {Impaired reliability and precision of spiking in adults but not juveniles in a mouse model of Fragile X Syndrome.}, journal = {eNeuro}, year = {2019}, month = {2019 Nov 04}, abstract = {

Fragile X Syndrome (FXS) is the most common source of intellectual disability and autism. Extensive studies have been performed on the network and behavioral correlates of the syndrome but our knowledge about intrinsic conductance changes is still limited. In this study we show a differential effect of FMRP Knock Out (KO) in different sub-sections of hippocampus using whole cell patch clamp in mouse hippocampal slices. We observed no significant change in spike numbers in the CA1 region of hippocampus but a significant increase in CA3, in juvenile mice. However, in adult mice we see a reduction in spike number in the CA1 with no significant difference in CA3. In addition, we see increased variability in spike number in CA1 cells following a variety of steady and modulated current step protocols. This effect emerges in adult (8 weeks) but not juvenile (4 weeks) mice. This increased spiking variability was correlated with reduced spike number and with elevated AHP. The increased AHP arose from elevated SK currents (small conductance calcium activated potassium channels) but other currents involved in mAHP, such as I and M, were not significantly different. We obtained a partial rescue of the cellular variability phenotype when we blocked SK current using the specific blocker apamin. Our observations provide a single cell correlate of the network observations of response variability and loss of synchronization, and suggest that elevation of SK currents in FXS may provide a partial mechanistic explanation for this difference. Fragile-X syndrome leads to a range of intellectual disability effects and autism. We have found differential effect of FMRP KO in different sub sections of hippocampus where it caused an increased spiking in CA3 in juveniles and reduced spiking in CA1, in adults. We have also found that even individual neurons with this mutation exhibit increased variability in their activity patterns. Importantly, this effect emerges after six weeks of age in mice. We showed that a specific ion channel protein, SK channel, was partially responsible, and blockage of these channels led to a partial restoration of cellular activity. This is interesting as it provides a possible molecular link between activity variability in single cells, and reported irregularity in network activity.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0217-19.2019}, author = {Dwivedi, Deepanjali and Chattarji, Sumantra and Bhalla, Upinder S} } @article {64328, title = {Implications of the null mutation for synapsin phosphorylation, longevity, climbing, and behavioural plasticity in adult .}, journal = {J Exp Biol}, year = {2019}, month = {2019 Sep 05}, abstract = {

The gene of encodes a highly abundant 47 kDa synaptic vesicle-associated protein. null mutants show defects in synaptic plasticity and larval olfactory associative learning but the molecular function of Sap47 at the synapse is unknown. We demonstrate that Sap47 modulates the phosphorylation of another highly abundant conserved presynaptic protein, synapsin. Site-specific phosphorylation of synapsin has repeatedly been shown to be important for behavioural plasticity but information of where in the brain phospho-synapsin isoforms are localized has been lacking. Here we report the distribution of serine-6-phosphorylated synapsin in the adult brain and show that it is highly enriched in rings of synapses in the ellipsoid body, and in large synapses near the lateral triangle. Effects of knock-out of or on olfactory associative learning/memory are compatible with the hypothesis that both proteins operate in the same molecular pathway. We therefore asked if this might also hold for other aspects of their function. We show that knock-out of but not reduces life span, whereas knock-out of , or both affects climbing as well as plasticity in circadian rhythms and sleep. Furthermore, electrophysiological assessment of synaptic properties at the larval neuromuscular junction (NMJ) reveals increased spontaneous synaptic vesicle fusion and reduced paired pulse facilitation in and single and double mutants. Our results imply that Sap47 and synapsin cooperate non-uniformly in the control of synaptic properties in different behaviourally relevant neuronal networks of the fruitfly.

}, issn = {1477-9145}, doi = {10.1242/jeb.203505}, author = {Blanco-Redondo, Beatriz and Nuwal, Nidhi and Kneitz, Susanne and Nuwal, Tulip and Halder, Partho and Liu, Yiting and Ehmann, Nadine and Scholz, Nicole and Mayer, Annika and Kleber, J{\"o}rg and K{\"a}hne, Thilo and Schmitt, Dominique and Sadanandappa, Madhumala K and Funk, Natalja and Albertova, Viera and Helfrich-F{\"o}rster, Charlotte and Ramaswami, Mani and Hasan, Gaiti and Kittel, Robert J and Langenhan, Tobias and Gerber, Bertram and Buchner, Erich} } @article {51000, title = {INDEX-db: The Indian Exome Reference Database (Phase I).}, journal = {J Comput Biol}, year = {2019}, month = {2019 Jan 07}, abstract = {

Deep sequencing-based genetic mapping has greatly enhanced the ability to catalog variants with plausible disease association. Confirming how these identified variants contribute to specific disease conditions, across human populations, poses the next challenge. Differential selection pressure may impact the frequency of genetic variations, and thus detection of association with disease conditions, across populations. To understand genotype to phenotype correlations, it thus becomes important to first understand the spectrum of genetic variation within a population by creating a reference map. In this study, we report the development of phase I of a new database of genetic variations called INDian EXome database (INDEX-db), from the Indian population, with an aim to establish a centralized database of integrated information. This could be useful for researchers involved in studying disease mechanisms at clinical, genetic, and cellular levels.

}, issn = {1557-8666}, doi = {10.1089/cmb.2018.0199}, author = {Ahmed P, Husayn and V, Vidhya and More, Ravi Prabhakar and Viswanath, Biju and Jain, Sanjeev and Rao, Mahendra S and Mukherjee, Odity} } @article {53183, title = {Insights from distribution dynamics inform strategies to conserve a dhole Cuon alpinus metapopulation in India.}, journal = {Sci Rep}, volume = {9}, year = {2019}, month = {2019 Feb 28}, pages = {3081}, abstract = {

Most large carnivore populations currently occur in heterogeneous landscapes, with source populations embedded in a matrix of human-dominated habitats. Understanding changes in distribution of endangered carnivores is critical for prioritizing and implementing conservation strategies. We examined distribution and dynamics of a dhole Cuon alpinus metapopulation, first in 2007 and subsequently in 2015, based on indirect sign surveys across 37, 000sq. km of India{\textquoteright}s Western Ghats. Predicted dhole occupancy declined from 0.62 (95\% CI: 0.58-0.66) in 2007 to 0.54 (95\% CI: 0.50-0.58) in 2015. Occupancy was associated with abundance of primary prey species and anthropogenic disturbance. Local extinction appeared to be influenced by forest cover loss, and offset by protected reserves; colonization was influenced by occupancy in neighbouring sites. Perturbation analysis indicated that occupancy was more sensitive to local extinction within reserves and to colonization in sites abutting reserves. The Western Ghats could serve as a stronghold for the endangered dhole, provided future colonizations are facilitated through habitat consolidation beyond reserve boundaries, and local extinctions are prevented by increasing protection efforts within select reserves. We advocate for wildlife managers to adopt a landscape-based approach and periodic monitoring to ensure persistence of the dhole metapopulation in Western Ghats, and in other critical conservation regions across the species{\textquoteright} geographic range.

}, issn = {2045-2322}, doi = {10.1038/s41598-019-39293-0}, author = {Srivathsa, Arjun and Karanth, K Ullas and Kumar, N Samba and Oli, Madan K} } @article {59720, title = {Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading.}, journal = {Cell}, volume = {177}, year = {2019}, month = {2019 Jun 13}, pages = {1738-1756.e23}, abstract = {

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a major class of lipid-anchored plasma membrane proteins. GPI-APs form nanoclusters generated by cortical acto-myosin activity. While our understanding of the physical principles governing this process is emerging, the molecular machinery and functional relevance of GPI-AP nanoclustering are unknown. Here, we first show that a membrane receptor signaling pathway directs nanocluster formation. Arg-Gly-Asp motif-containing ligands bound to the β1-integrin receptor activate src and focal adhesion kinases, resulting in RhoA signaling. This cascade triggers actin-nucleation via specific formins, which, along with myosin activity, drive the nanoclustering of membrane proteins with actin-binding domains. Concurrently, talin-mediated activation of the mechano-transducer vinculin is required for the coupling of the acto-myosin machinery to inner-leaflet lipids, thereby generating GPI-AP nanoclusters. Second, we show that these nanoclusters are functional; disruption of their formation either in GPI-anchor remodeling mutants or in vinculin mutants impairs cell spreading and migration, hallmarks of integrin function.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2019.04.037}, author = {Kalappurakkal, Joseph Mathew and Anilkumar, Anupama Ambika and Patra, Chandrima and van Zanten, Thomas S and Sheetz, Michael P and Mayor, Satyajit} } @article {67819, title = {Interacting effects of vessel noise and shallow river depth elevate metabolic stress in Ganges river dolphins.}, journal = {Sci Rep}, volume = {9}, year = {2019}, month = {2019 Oct 28}, pages = {15426}, abstract = {

In riverine {\textquoteright}soundscapes{\textquoteright}, complex interactions between sound, substrate type, and depth create difficulties in assessing impacts of anthropogenic noise pollution on freshwater fauna. Underwater noise from vessels can negatively affect endangered Ganges river dolphins (Platanista gangetica), which are {\textquoteright}almost blind{\textquoteright} and rely entirely on high-frequency echolocation clicks to sense their environment. We conducted field-based acoustic recordings and modelling to assess acoustic responses of Platanista to underwater noise exposure from vessels in the Ganga River (India), which is now being transformed into a major waterway. Dolphins showed enhanced activity during acute noise exposure and suppressed activity during chronic exposure. Increase in ambient noise levels altered dolphin acoustic responses, strongly masked echolocation clicks, and more than doubled metabolic stress. Noise impacts were further aggravated during dry-season river depth reduction. Maintaining ecological flows, downscaling of vessel traffic, and propeller modifications to reduce cavitation noise, could help mitigate noise impacts on Ganges river dolphins.

}, issn = {2045-2322}, doi = {10.1038/s41598-019-51664-1}, author = {Dey, Mayukh and Krishnaswamy, Jagdish and Morisaka, Tadamichi and Kelkar, Nachiket} } @article {50998, title = {Interface residues of transient protein-protein complexes have extensive intra-protein interactions apart from inter-protein interactions.}, journal = {Biol Direct}, volume = {14}, year = {2019}, month = {2019 Jan 15}, pages = {1}, abstract = {

BACKGROUND: Protein-protein interactions are crucial for normal biological processes and to regulate cellular reactions that affect gene expression and function. Several previous studies have emphasized the roles of residues at the interface of protein-protein complexes in conferring stability and specificity to the complex. Interface residues in a protein are well known for their interactions with sidechain and main chain atoms with the interacting protein. However, the extent of intra-protein interactions involving interface residues in a protein-protein complex and their relative contribution in comparison to inter-protein interactions are not clearly understood. This paper probes this feature using a dataset of protein-protein complexes of known 3-D structure.

RESULTS: We have analysed a dataset of 45 transient protein-protein complex structures with at least one of the interacting proteins with a known structure available also in the unbound form. We observe that a large proportion of interface residues (1608 out of 2137 interface residues, 75\%) are involved in intra and inter-protein interactions simultaneously. The amino acid propensities of such interfacial residues involved in bifurcated interactions are found to be highly similar to the general propensities to occur at protein-protein interfaces. Finally, we observe that a majority (83\%) of intra-protein interactions of interface residues with bifurcated interactions, are also observed in the protein uncomplexed form.

CONCLUSIONS: We have shown, to the best of our knowledge for the first time, that a vast majority of the protein-protein interface residues are involved in extensive intra-protein interactions apart from inter-protein interactions. For a majority of such interface residues the microenvironment in the tertiary structure is pre-formed and retained upon complex formation with its cognate partner during transient interactions.

REVIEWERS: This article was reviewed by Arumay Pal and Mallur Madhusudhan.

}, issn = {1745-6150}, doi = {10.1186/s13062-019-0232-2}, author = {Jayashree, Srinivasan and Murugavel, Pavalam and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {59702, title = {Interventions after acute stress prevent its delayed effects on the amygdala.}, journal = {Neurobiol Stress}, volume = {10}, year = {2019}, month = {2019 Feb}, pages = {100168}, abstract = {

Stress is known to elicit contrasting patterns of plasticity in the amygdala and hippocampus. While chronic stress leads to neuronal atrophy in the rodent hippocampus, it has the opposite effect in the basolateral amygdala (BLA). Further, even a single episode of acute stress is known to elicit delayed effects in the amygdala. For example, 2 h of immobilisation stress has been shown to cause a delayed increase in dendritic spine density on BLA principal neurons 10 days later in young rats. This is paralleled by higher anxiety-like behaviour at the same delayed time point. This temporal build-up of morphological and behavioural effects 10 days later, in turn, provides a stress-free time window of intervention after exposure to acute stress. Here, we explore this possibility by specifically testing the efficacy of an anxiolytic drug in reversing the delayed effects of acute immobilisation stress. Oral gavage of diazepam 1 h immobilisation stress prevented the increase in anxiety-like behaviour on the elevated plus-maze 10 days later. The same post-stress intervention also prevented delayed spinogenesis in the BLA 10 days after acute stress. Surprisingly, gavage of only the vehicle also had a protective effect on both the behavioural and synaptic effects of stress 10 days later. Vehicle gavage was found to trigger a significant rise in corticosterone levels that was comparable to that elicited by acute stress. This suggests that a surge in corticosterone levels, caused by the vehicle gavage 1 h after acute stress, was capable of reversing the delayed enhancing effects of stress on anxiety-like behaviour and BLA synaptic connectivity. These findings are consistent with clinical reports on the protective effects of glucocorticoids against the development of symptoms of post-traumatic stress disorder. Taken together, these results reveal strategies, targeted 1 h after stress, which can prevent the delayed effects of a brief exposure to a severe physical stressor.

}, issn = {2352-2895}, doi = {10.1016/j.ynstr.2019.100168}, author = {Chakraborty, Prabahan and Chattarji, Sumantra} } @article {68511, title = {Introducing the Mechanical Forces in Biochemistry Special Issue.}, journal = {Biochemistry}, volume = {58}, year = {2019}, month = {2019 Nov 26}, pages = {4655-4656}, issn = {1520-4995}, doi = {10.1021/acs.biochem.9b00999}, author = {Udgaonkar, Jayant B} } @article {47058, title = {IP3 receptors and Ca2+ entry}, journal = {Biochim Biophys Acta Mol Cell Res}, volume = {1866}, year = {2019}, month = {2018 Nov 15}, pages = {1092-1100}, abstract = {

Inositol 1,4,5-trisphosphate receptors (IPR) are the most widely expressed intracellular Ca release channels. Their activation by IP and Ca allows Ca to pass rapidly from the ER lumen to the cytosol. The resulting increase in cytosolic [Ca] may directly regulate cytosolic effectors or fuel Ca uptake by other organelles, while the decrease in ER luminal [Ca] stimulates store-operated Ca entry (SOCE). We are close to understanding the structural basis of both IPR activation, and the interactions between the ER Ca-sensor, STIM, and the plasma membrane Ca channel, Orai, that lead to SOCE. IPRs are the usual means through which extracellular stimuli, through ER Ca release, stimulate SOCE. Here, we review evidence that the IPRs most likely to respond to IP are optimally placed to allow regulation of SOCE. We also consider evidence that IPRs may regulate SOCE downstream of their ability to deplete ER Ca stores. Finally, we review evidence that IPRs in the plasma membrane can also directly mediate Ca entry in some cells.

}, issn = {1879-2596}, doi = {10.1016/j.bbamcr.2018.11.007}, author = {Thillaiappan, Nagendra Babu and Chakraborty, Pragnya and Hasan, Gaiti and Taylor, Colin W} } @article {48889, title = {Isolation and molecular characterization of Dengue virus clinical isolates from pediatric patients in New Delhi.}, journal = {Int J Infect Dis}, volume = {84}, year = {2019}, month = {07/2019}, pages = {S25-S33}, abstract = {

OBJECTIVES: To characterize the in vitro replication fitness, viral diversity and phylogeny of dengue viruses (DENV) isolated from Indian patients.

METHODS: DENV was isolated from whole blood collected from patients by passaging in cell culture. Passage 3 viruses were used for growth kinetics in C6/36 mosquito cells. Parallel efforts also focused on isolation of DENV RNA from plasma samples of the same patients and processed for next generation sequencing.

RESULTS: We were able to isolate 64 clinical isolates, mostly DENV-2, of which 25 were further used for growth curve analysis in vitro which showed a wide range of replication kinetics. Highest viral titers were of isolates from dengue with warning signs and severe dengue cases. We obtained full genome sequences of 21 DENV isolates. Genome analysis mapped the circulating DENV-2 strains to the Cosmopolitan genotype.

CONCLUSIONS: The replication kinetics of isolates from patients with mild or severe infection was not significantly different but the viral titers between the isolates varied by two orders of magnitude suggesting differences in replication fitness among the circulating DENV-2 isolates.

}, issn = {1878-3511}, doi = {10.1016/j.ijid.2018.12.003}, author = {Kar, Meenakshi and Nisheetha, Amul and Kumar, Anuj and Jagtap, Suraj and Shinde, Jitendra and Singla, Mohit and M, Saranya and Pandit, Awadhesh and Chandele, Anmol and Kabra, Sushil K and Krishna, Sudhir and Roy, Rahul and Lodha, Rakesh and Pattabiraman, Chitra and Medigeshi, Guruprasad R} } @article {62917, title = {Landing maneuvers of houseflies on vertical and inverted surfaces.}, journal = {PLoS One}, volume = {14}, year = {2019}, month = {2019}, pages = {e0219861}, abstract = {

Landing maneuvers of flies are complex behaviors which can be conceptually decomposed into sequences of modular actions, including body-deceleration, leg-extension, and body rotations. These behavioral {\textquoteright}modules{\textquoteright} must be coordinated to ensure well-controlled landing. The composite nature of these behaviors induces kinematic variability, making it difficult to identify the central rules that govern landing. Many previous studies have relied on tethered preparations to study landing behaviors, but tethering induces experimental artefacts by forcing some behaviors to operate in open-feedback control loop while others remain closed-loop. On the other hand, it is harder for the experimenter to control the stimuli experienced by freely-flying insects. One approach towards understanding general mechanisms of landing is to determine the common elements of their kinematics on surfaces of different orientations. We conducted a series of experiments in which the houseflies, Musca domestica, were lured to land on vertical (wall landings) or inverted (ceiling landings) substrates, while their flight was recorded with multiple high-speed cameras. We observed that, in both cases, well-controlled landings occurred when the distance at which flies initiated deceleration was proportional to flight velocity component in the direction of substrate. The ratio of substrate distance and velocity at onset of deceleration (tau) was conserved, despite substantial differences in mechanics of vertical vs. ceiling landings. When these conditions were not satisfied, their landing performance was compromised, causing their heads to collide into the substrate. Unlike body-deceleration, leg-extension in flies was independent of substrate distance or approach velocity. Thus, the robust reflexive visual initiation of deceleration is independent of substrate orientation, and combines with a more variable initiation of leg-extension which depends on surface orientation. Together, these combinations of behaviors enable flies to land in a versatile manner on substrates of various orientations.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0219861}, author = {Balebail, Sujay and Raja, Sathish K and Sane, Sanjay P} } @article {69322, title = {Large herbivores maintain a two-phase herbaceous vegetation mosaic in a semi-arid savanna.}, journal = {Ecol Evol}, volume = {9}, year = {2019}, month = {2019 Nov}, pages = {12779-12788}, abstract = {

Many arid and semi-arid rangelands exhibit distinct spatial patterning of vegetated and bare soil-dominated patches. The latter potentially represent a grazing-induced, degraded ecosystem state, but could also arise via mechanisms related to feedbacks between vegetation cover and soil moisture availability that are unrelated to grazing. The degree to which grazing contributes to the formation or maintenance of degraded patches has been widely discussed and modeled, but empirical studies of the role of grazing in their formation, persistence, and reversibility are limited.We report on a long-term (17\ years) grazing removal experiment in a semi-arid savanna where vegetated patches composed of perennial grasses were interspersed within large (\>10\ m) patches of bare soil.Short-term (3\ years) grazing removal did not allow bare patches to become revegetated, whereas following long-term (17\ years) grazing removal, bare soil patches were revegetated by a combination of stoloniferous grasses and tufted bunchgrasses. In the presence of grazers, stoloniferous grasses partially recolonized bare patches, but this did not lead to full recovery or to the establishment of tufted bunchgrasses.These results show that grazers alter both the balance between bare and vegetated patches, as well as the types of grasses dominating both patch types in this semiarid savanna.Synthesis: Large herbivores fundamentally shaped the composition and spatial pattern of the herbaceous layer by maintaining a two-phase herbaceous mosaic. However, bare patches within this mosaic can recover given herbivore removal over sufficiently long time scales, and hence do not represent a permanently degraded ecosystem state.

}, issn = {2045-7758}, doi = {10.1002/ece3.5750}, author = {Augustine, David J and Wigley, Benjamin J and Ratnam, Jayashree and Kibet, Staline and Nyangito, Moses and Sankaran, Mahesh} } @article {53173, title = {Latitude and live coral cover independently affect Chaetodontid and Pomacanthid fish community distribution in the Andaman and Nicobar archipelago, India}, journal = {MARINE BIODIVERSITY}, volume = {49}, year = {2019}, month = {02/2019}, pages = {235-245}, abstract = {

Empirical evidence indicates that for two reef fish groups, chaetodontids and pomacanthids, live coral cover and latitude determine the local abundance and species richness patterns. Most studies have considered the influence of either live coral cover or latitude in isolation, and the interactive effects that are likely to influence the geographical distribution in species richness and diversity has not been explored. In this study we explored the relationship between (1) species richness and latitude, and (2) species richness and benthic variables, (3) species diversity and latitude and (4) species diversity and benthic variables for butterflyfish (Chaetodontidae) and angelfish (Pomacanthidae) at 75 sites across 51 islands in the Andaman and Nicobar (A \& N) archipelago. A total of 30 species of chaetodontids belonging to four genera and 13 species of pomacanthids belonging to nine genera were recorded. We found that live coral cover and latitude were the best predictors for explaining variation in the distribution of these fish communities across the A \& N archipelago. This is probably because of the high dependence of these two fish groups on live coral cover and Nicobar{\textquoteright}s geographical proximity to the Coral Triangle, which is considered to be the center of origin of coral reefs and supports high biodiversity. Our results show that despite the high dependence of chaetodontids and pomacanthids on live coral cover, reduction of live coral cover due to a series of disturbance events had limited influence on species richness of these two fish groups, indicating that broad geographical trends are important in explaining variation in species richness for chaetodontid and pomacanthid fish groups.

}, doi = {10.1007/s12526-017-0790-4}, author = {Patankar, V and D{\textquoteright}Souza, E and Marathe, A} } @article {53188, title = {Learning of monochromatic stimuli in Apis cerana and Apis mellifera by means of PER conditioning.}, journal = {J Insect Physiol}, volume = {114}, year = {2019}, month = {2019 Feb 15}, pages = {30-34}, abstract = {

Honey bees are globally distributed and have received increased attention due to their high economic and ecological value for pollination, their exceptional eusocial lifestyle and complex behavioral repertoire. Interestingly, most research on learning and memory in honey bees has been performed in the Western honey bee, Apis mellifera L., and other honey bee species were largely neglected. In the current study, we thus compared visual learning performance of A. mellifera and the Eastern honey bee, A. cerana Fabr., using the proboscis extension response (PER) paradigm. Workers of A. mellifera and A. cerana were differentially conditioned to two monochromatic light stimuli, with peak maxima at 435 and 528 nm. Both honey bee species were able to form an association between the color stimulus and a sugar reward and significantly distinguished between the two color stimuli in a differential discrimination test. However, besides similar performance levels during visual learning, A. cerana showed a reduced mid-term memory (tested after 2 h) compared to A. mellifera. Finally, performance of the visual PER conditioning in our study reached similar levels as found in olfactory PER conditioning, and we thus recommend the visual PER conditioning approach in addition to olfactory conditioning as a useful tool for studying species-specific learning and memory capabilities in honey bees under controlled laboratory conditions.

}, issn = {1879-1611}, doi = {10.1016/j.jinsphys.2019.02.006}, author = {Lichtenstein, Leonie and Brockmann, Axel and Spaethe, Johannes} } @article {59706, title = {Live-Cell Fluorescence Imaging of RecN in Caulobacter crescentus Under DNA Damage.}, journal = {Methods Mol Biol}, volume = {2004}, year = {2019}, month = {2019}, pages = {239-250}, abstract = {

Structural maintenance of chromosomes (SMC) proteins play a central role in the organization, segregation and maintenance of chromosomes across domains of life. In bacteria, an SMC-family protein, RecN, has been implicated to have important functions in DNA damage repair. Recent studies have suggested that RecN is required to increase chromosome cohesion in response to DNA damage and may also stimulate specific events during recombination-based repair. While biochemical and genetic assays provide insights into mechanism of action of RecN and other repair factors, in vivo understanding of activity and regulation of proteins can be predominantly gained via microscopy-based approaches. Here, we describe a protocol to study the localization of fluorescently tagged RecN to a site-specific double-strand break (DSB) in Caulobacter crescentus. We further outline a method to probe RecN dynamics in cells with a single, nonreplicating chromosome. This technique can be used to study the early steps of recombination-based repair and understand the regulation of protein recruitment to and further association with sites of damage.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-9520-2_18}, author = {Chimthanawala, Afroze and Badrinarayanan, Anjana} } @article {54454, title = {Local Determinants of the Mutational Landscape of the Human Genome.}, journal = {Cell}, volume = {177}, year = {2019}, month = {2019 Mar 21}, pages = {101-114}, abstract = {

Large-scale chromatin features, such as replication time and accessibility influence the rate of somatic and germline mutations at the megabase scale. This article reviews how local chromatin structures -e.g., DNA wrapped around nucleosomes, transcription factors bound to DNA- affect the mutation rate at a local scale. It dissects how the interaction of some mutagenic agents and/or DNA repair systems with these local structures influence the generation of mutations. We discuss how this local mutation rate variability affects our understanding of the evolution of the genomic sequence, and the study of the evolution of organisms and tumors.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2019.02.051}, author = {Gonzalez-Perez, Abel and Sabarinathan, Radhakrishnan and Lopez-Bigas, Nuria} } @article {68514, title = {A locomotor assay reveals deficits in heterozygous Parkinson{\textquoteright}s disease model and proprioceptive mutants in adult .}, journal = {Proc Natl Acad Sci U S A}, year = {2019}, month = {2019 Nov 20}, abstract = {

Severe locomotor impairment is a common phenotype of neurodegenerative disorders such as Parkinson{\textquoteright}s disease (PD). models of PD, studied for more than a decade, have helped in understanding the interaction between various genetic factors, such as and PINK1, in this disease. To characterize locomotor behavioral phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behavior is important to understand the manifestation of locomotor disorders. We introduce a climbing behavior assay which provides such fine-scale behavioral data and tests this proposition for the model. We use this inexpensive, fully automated assay to quantitatively characterize the climbing behavior at high parametric resolution in 3 contexts. First, we characterize wild-type flies and uncover a hitherto unknown sexual dimorphism in climbing behavior. Second, we study climbing behavior of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation ( ) known to affect fine motor control in Moreover, we identify aberrant geotactic behavior in mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviors of wild-type and mutant flies in fine detail and can reveal subtle motor defects.

}, issn = {1091-6490}, doi = {10.1073/pnas.1807456116}, author = {Aggarwal, Aman and Reichert, Heinrich and VijayRaghavan, K} } @article {50996, title = {Maintenance of Rhodopsin levels in Drosophila photoreceptor and phototransduction requires Protein Kinase D.}, journal = {Fly (Austin)}, year = {2019}, month = {2019 Jan 21}, abstract = {

During Drosophila phototransduction, the G protein coupled receptor (GPCR) Rhodopsin (Rh1) transduces photon absorption into electrical signal via G-protein coupled activation of phospholipase C (PLC). Rh1 levels in the plasma membrane are critical for normal sensitivity to light. In this study, we report that Protein kinase D (dPKD) regulates Rh1 homeostasis in adult photoreceptors. Although eye development and retinal structure are unaffected in the dPKD hypomorph (dPKD), it exhibited elevated levels of Rh1. Surprisingly, despite having elevated levels of Rh1, no defect was observed in the electrical response to light in these flies. By contrast the levels of another transmembrane protein of the photoreceptor plasma membrane, Transient receptor potential (TRP) was not altered in dPKD. Our results indicate that dPKD is dispensable for eye development but is required for maintaining Rh1 levels in adult photoreceptors.

}, issn = {1933-6942}, doi = {10.1080/19336934.2019.1565256}, author = {Ashe, Sudipta and Yadav, Shweta} } @article {45302, title = {Mass Spectrometric Quantification of Arousal Associated Neurochemical Changes in Single Honey Bee Brains and Brain Regions.}, journal = {ACS Chem Neurosci}, volume = {10}, year = {2019}, month = {2018 Oct 26}, pages = {950-1959}, abstract = {

Honey bee foragers show a strong diurnal rhythm of foraging activity, and such behavioral changes are likely under the control of specific neuromodulators. To identify and quantify neuromodulators involved in regulating rest and arousal in honey bees, we established a mass spectrometric method for quantifying 14 different neurochemicals and precursor molecules. We measured forager type and brain region specific differences in amine levels from individual honey bee brains and brain regions. The observed differences in amine levels between resting and aroused foragers resemble findings in other species indicating a conserved molecular mechanism by glutamate and GABA in regulating arousal. Subesophageal ganglion specific changes in the histaminergic system and global increases in aspartate during arousal suggest a possible role of histamine and aspartate in feeding and arousal, respectively. More aminergic systems were significantly affected due to arousal in nectar foragers than in pollen foragers, implying that forager phenotypes differ not only in their food preference but also in their neuromodulatory signaling systems (brain states). Finally, we found that neurotransmitter precursors were better at distinguishing brain states in the central brain, while their end products correlated with arousal associated changes in sensory regions like the optic and antennal lobes.

}, issn = {1948-7193}, doi = {10.1021/acschemneuro.8b00254}, author = {Ramesh, Divya and Brockmann, Axel} } @article {74436, title = {MCV Truncated Large T antigen interacts with BRD4 in tumors}, journal = {Matters}, year = {2019}, month = {01/2019}, abstract = {

Among Polyomaviridae family of viruses, Merkel Cell Polyomavirus (MCV) is the only human polyomavirus with convincing data supporting its classification as a direct causative agent of a human skin malignancy, Merkel Cell Carcinoma. Oncogenic transformation by MCV requires the integration of the viral genome into the human genome, truncation of the large T antigen (LT) to render the viral genome replication deficient and expression of small T antigen oncoprotein. The chromatin binding protein BRD4, was recently shown to transcriptionally regulate the expression of virus oncoproteins, thereby enhancing the tumorigenesis of virus-associated cancers, such as HPV associated cervical cancer. Previous work by Wang et al. revealed that BRD4 interacts with MCV full length LT during viral replication. In this study, we demonstrated that MCV truncated tumor LT antigen also interacts with BRD4 protein. We showed that the MCV tumor LT antigen and BRD4 protein complex co-localizes within the nucleus. Furthermore, we tested whether BRD4 protein transcriptionally regulates MCV Non Coding Control Region (NCCR), where we found that though full length LT and sT together, along with the BRD4 protein showed enhanced transcriptional activity whereas tumor truncated LT did not. These findings on the interactions of the MCV tumor truncated LT antigen with the BRD4 protein add to existing knowledge about interactions with LT and its role in tumorigenesis, and assist in efforts to more precisely define new therapy targets for this disease.

}, doi = {10.19185/matters.201811000004}, author = {Arora, Reety and Vats, A and Chimankar, V} } @article {62768, title = {Measurement of Store-Operated Calcium Entry in Human Neural Cells: From Precursors to Differentiated Neurons.}, journal = {Methods Mol Biol}, volume = {2029}, year = {2019}, month = {2019}, pages = {257-271}, abstract = {

Calcium imaging in an ex-vivo\ setup is used to understand the calcium status of isolated cells or tissue. In this chapter we explain the use of the ratiometric chemical indicator Fura-2 which can be loaded into isolated cells in the form of lipophilic acetomethyl (AM) esters. Fura-2 is a combination of calcium chelator and fluorophore, and can be used with dual wavelength excitation (340/380\ nm) for quantitative calcium concentrations. The cells can then be viewed using a fluorescence microscope and captured by a CCD camera. We specifically discuss the technique involved in understanding the endoplasmic reticulum (ER)-driven store-operated calcium entry (SOCE) in human neural precursors (NPCs)\ and spontaneously differentiated neurons derived from a pluripotent human\ embryonic stem cell\ (hESC) line. The derivation of neural precursors from stem cells and their subsequent spontaneous neural differentiation is also explained. The method can be used for various non-excitable and excitable cell types including neurons, be it freshly isolated, from frozen vials, or derived from different stem cell lines.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-9631-5_20}, author = {Gopurappilly, Renjitha and Deb, Bipan Kumar and Chakraborty, Pragnya and Hasan, Gaiti} } @article {56128, title = {Mechanistic approaches to understand the prion-like propagation of aggregates of the human tau protein.}, journal = {Biochim Biophys Acta Proteins Proteom}, volume = {1867}, year = {2019}, month = {2019 Apr 12}, pages = {922-932}, abstract = {

The dynamic nature of the tau protein under physiological conditions is likely to be critical for it to perform its diverse functions inside a cell. Under some conditions, this intrinsically disordered protein assembles into pathogenic aggregates that are self-perpetuating, toxic and infectious in nature. The role of liquid-liquid phase separation in the initiation of the aggregation reaction remains to be delineated. Depending on the nature of the aggregate, its structure, and its localization, neurodegenerative disorders with diverse clinical features are manifested. The prion-like mechanism by which these aggregates propagate and spread across the brain is not well understood. Various factors (PTMs, mutations) have been strongly associated with the pathological aggregates of tau. However, little is known about how these factors modulate the pathological properties linked to aggregation. This review describes the current progress towards understanding the mechanism of propagation of tau aggregates.

}, issn = {1878-1454}, doi = {10.1016/j.bbapap.2019.04.004}, author = {Kumar, Harish and Udgaonkar, Jayant B} } @article {66090, title = {Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.}, journal = {Microb Pathog}, year = {2019}, month = {2019 Oct 07}, pages = {103778}, abstract = {

Merkel cell carcinoma is a rare, lethal cancer histopathologically composed of cells showing similarity with mechanoreceptor Merkel cells. Merkel cell tumors manifest in two distinct forms. While a virus called Merkel cell polyomavirus is involved in the pathogenesis of one form of Merkel tumor, the other is driven by ultraviolet (UV)-linked mutations. In this study we investigated 18 cases, from the Indian population, of Merkel cell carcinoma for immunohistochemical (IHC) expression of Merkel cell polyomavirus (MCV) T antigen, including 12 cases tested by PCR, to identify viral etiopathology. We tested the tumors with two sensitive antibodies (CM2B4 and Ab3), targeting the viral large T antigen protein and with PCR primers targeting the N terminus of T antigen. Overall, we observed 38.8\% (7/18) tumors displaying positive IHC expression of Merkel cell polyomavirus T antigen and 25\% (3/12) tumors showing positive results, by both, immunohistochemistry and PCR. This constitutes the first report from India showing implication of MCV in Merkel cell carcinomas. Moreover, this is one of the larger series of Merkel cell carcinomas, tested for MCV, by both immunohistochemistry and PCR, in this part of the world. These results further indicate that a slightly more number of such cases in India are likely to be caused by UV-linked damage, as opposed to Merkel cell polyomavirus mediated tumorigenesis, which is definitely implicated in a subset of cases.

}, issn = {1096-1208}, doi = {10.1016/j.micpath.2019.103778}, author = {Arora, Reety and Rekhi, Bharat and Chandrani, Pratik and Krishna, Sudhir and Dutt, Amit} } @article {60325, title = {Metabolic constraints drive self-organization of specialized cell groups.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Jun 26}, abstract = {

How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains unresolved. We find that within a mature, clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such self-assembly. Beginning in a uniformly gluconeogenic state, cells exhibiting a contrary, high pentose phosphate pathway activity state, spontaneously appear and proliferate, in a spatially constrained manner. Gluconeogenic cells in the colony produce and provide a resource, which we identify as trehalose. Above threshold concentrations of external trehalose, cells switch to the new metabolic state and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states.

}, issn = {2050-084X}, doi = {10.7554/eLife.46735}, author = {Varahan, Sriram and Walvekar, Adhish and Sinha, Vaibhhav and Krishna, Sandeep and Laxman, Sunil} } @article {56657, title = {Microsecond sub-domain motions and the folding and misfolding of the mouse prion protein.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Apr 26}, abstract = {

Protein aggregation appear to originate from partially unfolded conformations that are sampled through stochastic fluctuations of the native protein. It has been a challenge to characterize these fluctuations, under native like conditions. Here, the conformational dynamics of the full-length (23-231) mouse prion protein were studied under native conditions, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS). The slowest fluctuations could be associated with the folding of the unfolded state to an intermediate state, by the use of microsecond mixing experiments. The two faster fluctuations observed by PET-FCS, could be attributed to fluctuations within the native state ensemble. The addition of salt, which is known to initiate the aggregation of the protein, resulted in an enhancement in the time scale of fluctuations in the core of the protein. The results indicate the importance of native state dynamics in initiating the aggregation of proteins.

}, issn = {2050-084X}, doi = {10.7554/eLife.44766}, author = {Goluguri, Rama Reddy and Sen, Sreemantee and Udgaonkar, Jayant} } @article {59710, title = {miR828 and miR858 regulate VvMYB114 to promote anthocyanin and flavonol accumulation in grapes.}, journal = {J Exp Bot}, year = {2019}, month = {2019 May 30}, abstract = {

MicroRNAs are a class of non-coding small RNAs involved in negative regulation of gene expression and playing critical roles in developmental and metabolic pathways. Studies in several plants have identified few microRNAs and other small (s) RNAs that target regulators of phenylpropanoid metabolic pathway called MYB transcription factors. However, it is not well-understood how sRNA mediated regulation of MYBs influences accumulation of specific secondary metabolites. Using sRNA-sequencing, degradome analysis, mRNA-seq and proteomic analysis, we establish that grape lines with high anthocyanin content express two abundant MYB-targeting miRNAs resulting in differential expression of specific MYB proteins. miR828 and miR858 target coding sequences of specific helix motifs in the mRNA sequences of MYB proteins. Targeting by miR828, caused MYB RNA decay and production of cascade secondary siRNAs that depend on RNA dependant RNA polymerase 6. MYB suppression and cascade silencing was more robust in grape lines with high anthocyanin content when compared to a flavonol-rich grape line. We establish that miRNA-mediated silencing targeted repressor class of MYBs to promote anthocyanin biosynthesis in grape lines with high anthocyanins. We propose that this process regulates expression of appropriate MYBs in grape lines to produce specific secondary metabolites.

}, issn = {1460-2431}, doi = {10.1093/jxb/erz264}, author = {Tirumalai, Varsha and Swetha, Chenna and Nair, Ashwin and Pandit, Awadhesh and Shivaprasad, P V} } @article {51245, title = {Mismatch in receiver responses to multimodal signals in a diurnal gecko}, journal = {Animal Behaviour}, volume = {147}, year = {2019}, month = {01/2019}, pages = {115-123}, abstract = {

Multimodal signals are used by many animals for intraspecific communication and can provide information about sex identity as well as quality of the signaller. In diurnal geckos of the genus Cnemaspis, chromatic colour patches in males evolved after chemical secretions, providing us with an opportunity to examine the utility of evolving multimodality. We quantified signal components and receiver responses in Cnemaspis mysoriensis to determine the relative importance of chemical and visual traits for intraspecific communication. Digital imagery and spectrophotometry of lizards revealed the presence of two distinct male morphs (yellow-gular and white-gular) and one female form (white-gular). All males, but no females, had yellow eye rims. Characterization of chemical secretions from the ventral precloacal and femoral glands of all lizard forms revealed no differences between male morphs. However, all males differed from females in a few key compounds. We then exposed lizards to only chemical stimuli, only visual stimuli, or both chemical and visual stimuli of conspecific males and females. We found that females were responsive to the chemical stimuli alone as well as the multimodal stimuli of males, whereas males were only responsive to the multimodal stimuli of other males. Neither chemical or visual components of females elicited a response from conspecifics. Thus, while the chemical secretions of males are sufficient for females to elicit a response, multimodal stimuli are necessary for males to respond. Based on variation in signalling traits and receiver responses, we conclude that: (1) chemical secretions signal both sex identity and male quality; (2) eye rim colour encodes information about sex identity; and (3) gular colour in males is probably not a redundant trait, providing some information to males, but not females. We conclude that the secondary evolution of visual signals in C.\ mysoriensis therefore enhances male{\textendash}male social interactions and not communication in general.

}, doi = {10.1016/j.anbehav.2018.11.011}, author = {Kabir, Shakilur and Venkatesan, Radhika and Thaker, Maria} } @article {64899, title = {Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Sep 11}, pages = {4127}, abstract = {

Substrate channeling is a mechanism for the internal transfer of hydrophobic, unstable or toxic intermediates from the active site of one enzyme to another. Such transfer has previously been described to be mediated by a hydrophobic tunnel, the use of electrostatic highways or pivoting and by conformational changes. The enzyme PaaZ is used by many bacteria to degrade environmental pollutants. PaaZ is a bifunctional enzyme that catalyzes the ring opening of oxepin-CoA and converts it to 3-oxo-5,6-dehydrosuberyl-CoA. Here we report the structures of PaaZ determined by electron cryomicroscopy with and without bound ligands. The structures reveal that three domain-swapped dimers of the enzyme form a trilobed structure. A combination of small-angle X-ray scattering (SAXS), computational studies, mutagenesis and microbial growth experiments suggests that the key intermediate is transferred from one active site to the other by a mechanism of electrostatic pivoting of the CoA moiety, mediated by a set of conserved positively charged residues.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-11931-1}, author = {Sathyanarayanan, Nitish and Cannone, Giuseppe and Gakhar, Lokesh and Katagihallimath, Nainesh and Sowdhamini, Ramanathan and Ramaswamy, Subramanian and Vinothkumar, Kutti R} } @article {60327, title = {Monitoring site-specific conformational changes in real-time reveals a misfolding mechanism of the prion protein.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Jun 24}, abstract = {

During pathological aggregation, proteins undergo remarkable conformational re-arrangements to anomalously assemble into a heterogeneous collection of misfolded multimers, ranging from soluble oligomers to insoluble amyloid fibrils. Inspired by fluorescence resonance energy transfer (FRET) measurements of protein folding, an experimental strategy to study site-specific misfolding kinetics during aggregation, by effectively suppressing contributions from inter-molecular FRET, is described. Specifically, the kinetics of conformational changes across different secondary and tertiary structural segments of the mouse prion protein (moPrP) were monitored independently, after the monomeric units transformed into large oligomers O, which subsequently disaggregated reversibly into small oligomers O at pH 4. The sequence segments spanning helices α2 and α3 underwent a compaction during the formation of O and elongation into β-sheets during the formation of O. The β1-α1-β2 and α2-α3 subdomains were separated, and the helix α1 was unfolded to varying extents in both O and O.

}, issn = {2050-084X}, doi = {10.7554/eLife.44698}, author = {Sengupta, Ishita and Udgaonkar, Jayant} } @article {53618, title = {A multilocus phylogenetic framework of the tribe Aeromachini (Lepidoptera: Hesperiidae: Hesperiinae), with implications for taxonomy and biogeography}, journal = {Systematic Entomology}, year = {2019}, month = {01/2019}, abstract = {

The Oriental tribe Aeromachini (Lepidoptera: Hesperiidae: Hesperiinae) is diverse and widespread, but its monophyly and circumscription remain unresolved. In this study, we inferred phylogenetic relationships within the tribe using two mitochondrial (16S and COI-COII) and two nuclear genes (EF-1α and Wingless) from 71 samples representing all of the known genera of Aeromachini (s.l.). Phylogenetic topologies obtained from two model-based methods (maximum-likelihood and Bayesian inference) were largely congruent, showing that Aeromachini was monophyletic. Many genera within Aeromachini were polyphyletic, especially Arnetta, Thoressa, Ampittia and Sovia. Based on these results, we propose a new classification consisting of 14 genera, of which two are newly described: Halpemorpha gen.n. and Praethoressa gen.n. Ampittia and Ochus are restructured, with: (i) Ampittia nana and Ampittia dalailama moved to Aeromachus, (ii) new combinations proposed for the remaining Ampittia species, and (iii) a new combination, Ampittia subvittatus comb.n., proposed. The Oriental members of the genus Arnetta belong to this tribe, but the African Arnetta hyposticta was found to be embedded into the outgroup and closely related to Isoteinon. We propose that hyposticta be reinstated in the genus Galerga Mabille, along with two other African species (fito and ellipsis). Thoressa is polyphyletic, with three distinct lineages. The type species Thoressa masoni forms a clade closely related to the sister genera Sebastonyma and Parasovia. We thus describe Praethoressa gen.n. to include the species varia (formerly of Thoressa), and transfer the remaining Thoressa to Pedesta, which is confirmed as a valid genus. Although the relationships of some genera remained unsolved in our work, the present phylogenetic hypothesis will serve as a reference for further studies. A secondary calibration was used to estimate the divergence time, which indicated that the diversification of Aeromachini started in the late Eocene and early Oligocene (c. 34.22 Ma). Further, ancestral range estimates indicated that the common ancestor of Aeromachini originated in Southeast Asia. Diversification in situ and range expansion to adjacent areas have played essential roles in the evolution of Aeromachini, but founder-event speciation and vicariance also have likely been important factors in shaping the biogeographical history of this tribe.

}, doi = {10.1111/syen.12322}, author = {Huang, Zhen-Fu and Chiba, H and Jin, J and Kizhakke, AG and Wang, Min and Kunte, Krushnamegh and Fan, X} } @article {59717, title = {The multitasking abilities of MATE transporters in plants.}, journal = {J Exp Bot}, year = {2019}, month = {2019 May 18}, abstract = {

Plants, being sessile constantly monitor environmental cues and respond appropriately to modulate their growth and development. Membrane transporters, act as gatekeepers of the cell regulating both the inflow of useful materials as well as exudation of harmful substances from the cell. Multidrug and Toxic Compound Extrusion (MATE) family of transporters are ubiquitously present in almost all forms of life including prokaryotes and eukaryotes. In bacteria, the MATE proteins were originally characterized as efflux transporters conferring drug resistance. There are 58 MATE transporters in Arabidopsis thaliana also known as DETOXIFICATION (DTX) proteins. In plants, these integral membrane proteins perform a diverse array of functions ranging from secondary metabolite transport, xenobiotic detoxification, and aluminium tolerance to disease resistance. MATE proteins also regulate overall plant development by controlling phytohormone transport, tip growth processes and senescence. While most of the functional characterization of the MATE proteins has been reported in Arabidopsis, recent reports suggest their diverse roles in numerous plant species. The wide array of functions exhibited by MATE proteins, highlight their multitasking ability. In this review, we have integrated information related to structure and functions of MATE transporters in plants. Since these transporters are central to mechanisms that allow plants to adapt to abiotic and biotic stresses, study of these transporters can potentially contribute to stress tolerance under changing climatic conditions.

}, issn = {1460-2431}, doi = {10.1093/jxb/erz246}, author = {Upadhyay, Neha and Kar, Debojyoti and Deepak Mahajan, Bhagyashri and Nanda, Sanchali and Rahiman, Rini and Panchakshari, Nimisha Abhay and Bhagavatula, Lavanya and Datta, Sourav} } @article {59704, title = {New clues into the mechanisms of rice domestication.}, journal = {J Biosci}, volume = {44}, year = {2019}, month = {2019 Jun}, abstract = {

Domestication of rice involved incorporation of specific yield-related changes in wild species of rice. This agricultural process has been of significant interest for plant biologists. The recent advance in genomics has provided new tools to investigate the genetic basis and consequences of domestication. Several genes involved in domestication and diversification process have been characterized, and as expected, this list is over-represented by transcription factors and their cofactors. Most often the modification orchestrated expression levels of genes such as those coding for transcription factors. It has been proposed that transcriptional regulators and their regulation is likely a major theme controlling morphological differences between crops and their progenitors. However, recent data indicate that single amino acid changes in genes coding for key proteins as well as epigenetic and small RNA-mediated pathways also contributed towards domesticationassociated phenotypes.

}, issn = {0973-7138}, author = {Shivaprasad, Padubidri V} } @article {67822, title = {A new genus and species of natricine snake from northeast India.}, journal = {Zootaxa}, volume = {4603}, year = {2019}, month = {2019 May 09}, pages = {zootaxa.4603.2.2}, abstract = {

Based on the first molecular phylogenetic analyses of samples from northeast India, specimens referred to Rhabdops from this region are more closely related to the southeast and east Asian natricine genera Opisthotropis G{\"u}nther, 1872 and Sinonatrix Rossman Eberle, 1977 (as well as to New World and western Palearctic natricines) than to peninsular Indian (true) Rhabdops. Morphologically, these northeast Indian populations differ from other natricines by having a single ({\textquoteright}fused{\textquoteright} or unpaired) internasal shield and a single prefrontal shield. Given the morphological and phylogenetic distinctiveness of these northeast Indian populations, we refer them to a new genus, Smithophis gen. nov., and transfer Rhabdops bicolor (Blyth, 1854) to Smithophis bicolor comb. nov. Based on morphological and molecular variation within our northeast Indian sample, we additionally describe Smithophis atemporalis sp. nov. from the state of Mizoram.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4603.2.2}, author = {Giri, Varad B and Gower, David J and Das, Abhijit and Lalremsanga, H T and Lalronunga, Samuel and Captain, Ashok and Deepak, V} } @article {68510, title = {A new species of fossorial natricid snakes of the genus Trachischium G{\"u}nther, 1858 (Serpentes: Natricidae) from the Himalayas of northeastern India.}, journal = {C R Biol}, year = {2019}, month = {2019 Nov 19}, abstract = {

A new species of natricid snakes, Trachischium apteii sp. nov. is described from the northeastern Indian State of Arunachal Pradesh. The new species differs from its congeners in the following suite of characters: dorsal scales in 15:15:15 rows, SVL 293-299mm, higher ventral count 143-150, very faint dorsal longitudinal lines, absence of yellow patch on the neck and the belly being pale yellow. Preliminary discussion on the phylogenetic position of the members of the genus Trachischium is presented. This discovery of a new snake species advocates the need for dedicated surveys to document biodiversity across Arunachal Pradesh and the neighbouring States of northeastern India.

}, issn = {1768-3238}, doi = {10.1016/j.crvi.2019.10.003}, author = {Bhosale, Harshal S and Gowande, Gaurang G and Mirza, Zeeshan A} } @article {55803, title = {A new species of rock-dwelling Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from Tamil Nadu, southern India}, journal = {ZOOTAXA}, volume = {4571}, year = {2019}, month = {02/2019}, pages = { 383-397}, abstract = {

A new species of the gekkonid genus Cnemaspis is described based on a series of nine specimens from near Sankari in Salem district, Tamil Nadu state, southern India. The new species is diagnosable by the following suite of characters: a small-sized Cnemaspis (adult snout to vent length less than 33 mm); heterogeneous dorsal pholidosis consisting of weakly keeled granular scales intermixed with large strongly keeled, conical tubercles, 9{\textendash}11 rows of dorsal tubercles, 12{\textendash}17 tubercles in paravertebral rows; spine-like scales absent on flank, 17{\textendash}20 lamellae under digit IV of pes. Males with 4{\textendash}6 femoral pores on each thigh, separated on either side by eight poreless scales from four precloacal pores; precloacal pores separated medially by a single poreless scale; two single dorsal ocelli on occiput and between forelimb insertions, two pairs of ocelli on either side just anterior and posterior to forelimb insertions. Cnemaspis agarwali sp. nov. is the fifth endemic species of Cnemaspis from peninsular India outside the Western Ghats and highlights the rich and unique diversity of this understudied region.

}, doi = {10.11646/zootaxa.4571.3.6}, author = {Khandekar, A} } @article {62765, title = {NMDAR mediated translation at the synapse is regulated by MOV10 and FMRP.}, journal = {Mol Brain}, volume = {12}, year = {2019}, month = {2019 Jul 10}, pages = {65}, abstract = {

Protein synthesis is crucial for maintaining synaptic plasticity and synaptic signalling. Here we have attempted to understand the role of RNA binding proteins, Fragile X Mental Retardation Protein (FMRP) and Moloney Leukemia Virus 10 (MOV10) protein in N-Methyl-D-Aspartate Receptor (NMDAR) mediated translation regulation. We show that FMRP is required for translation downstream of NMDAR stimulation and MOV10 is the key specificity factor in this process. In rat cortical synaptoneurosomes, MOV10 in association with FMRP and Argonaute 2 (AGO2) forms the inhibitory complex on a subset of NMDAR responsive mRNAs. On NMDAR stimulation, MOV10 dissociates from AGO2 and promotes the translation of its target mRNAs. FMRP is required to form MOV10-AGO2 inhibitory complex and to promote translation of MOV10 associated mRNAs. Phosphorylation of FMRP appears to be the potential switch for NMDAR mediated translation and in the absence of FMRP, the distinct translation response to NMDAR\ stimulation is lost. Thus, FMRP and MOV10 have an important regulatory role in NMDAR mediated translation at the synapse.

}, issn = {1756-6606}, doi = {10.1186/s13041-019-0473-0}, author = {Kute, Preeti Madhav and Ramakrishna, Sarayu and Neelagandan, Nagammal and Chattarji, Sumantra and Muddashetty, Ravi S} } @article {66851, title = {Notch signalling in cervical cancer.}, journal = {Exp Cell Res}, year = {2019}, month = {2019 Oct 18}, pages = {111682}, abstract = {

The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in sub-sets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies. However, it has been more challenging to clearly define the role of the Notch pathway in human solid tumours, given the absence of widespread specific activating or repressive mutations in key components of the pathway. In this review, we trace more than two decades of work looking at the role of Notch signalling in human cervical cancer progression. We document the contrasting reports on a tumour suppressive role and pro-oncogenic role in cervical cancers. However, an analysis of recent genomic data strikingly shows both widespread features of Notch expression and genetic changes that largely amplify positive regulators and delete negative controllers of the Notch pathway. This analysis reinforces a largely pro-oncogenic role for Notch signalling and lays the foundation for a nuanced exploration of synergistic and targeted therapies. Lastly, we further trace some of the complex challenges in advanced cervical cancer progression, including issues of cancer stem cells and metastasis.

}, issn = {1090-2422}, doi = {10.1016/j.yexcr.2019.111682}, author = {Rodrigues, Calvin and Joy, Leanna R and Sachithanandan, Sasikala P and Krishna, Sudhir} } @article {66852, title = {A novel mass assay to measure phosphatidylinositol-5-phosphate from cells and tissues.}, journal = {Biosci Rep}, volume = {39}, year = {2019}, month = {2019 Oct 30}, abstract = {

Phosphatidylinositol-5-phosphate (PI5P) is a low abundance lipid proposed to have functions in cell migration, DNA damage responses, receptor trafficking and insulin signalling in metazoans. However, studies of PI5P function are limited by the lack of scalable techniques to quantify its level from cells and tissues in multicellular organisms. Currently, PI5P measurement requires the use of radionuclide labelling approaches that are not easily applicable in tissues or in vivo samples. In the present study, we describe a simple and reliable, non-radioactive mass assay to measure total PI5P levels from cells and tissues of Drosophila, a genetically tractable multicellular model. We use heavy oxygen-labelled ATP (18O-ATP) to label PI5P from tissue extracts while converting it into PI(4,5)P2 using an in vitro kinase reaction. The product of this reaction can be selectively detected and quantified with high sensitivity using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform. Further, using this method, we capture and quantify the unique acyl chain composition of PI5P from Drosophila cells and tissues. Finally, we demonstrate the use of this technique to quantify elevations in PI5P levels, from Drosophila larval tissues and cultured cells depleted of phosphatidylinositol 5 phosphate 4-kinase (PIP4K), that metabolizes PI5P into PI(4,5)P2 thus regulating its levels. Thus, we demonstrate the potential of our method to quantify PI5P levels with high sensitivity from cells and tissues of multicellular organisms thus accelerating understanding of PI5P functions in vivo.

}, issn = {1573-4935}, doi = {10.1042/BSR20192502}, author = {Ghosh, Avishek and Sharma, Sanjeev and Shinde, Dhananjay and Ramya, Visvanathan and Raghu, Padinjat} } @article {62759, title = {Observation of Continuous Contraction and a Metastable Misfolded State during the Collapse and Folding of a Small Protein.}, journal = {J Mol Biol}, year = {2019}, month = {2019 Jul 19}, abstract = {

To obtain proper insight into how structure develops during a protein folding reaction, it is necessary to understand the nature and mechanism of the polypeptide chain collapse reaction, which marks the initiation of folding. Here, the time-resolved fluorescence resonance energy transfer technique, in which the decay of the fluorescence light intensity with time is used to determine the time evolution of the distribution of intra-molecular distances, has been utilized to study the folding of the small protein, monellin. It is seen that when folding begins, about one-third of the protein molecules collapse into a molten globule state (I), from which they relax by continuous further contraction to transit to the native state. The larger fraction gets trapped into a metastable misfolded state. Exit from this metastable state occurs via collapse to the lower free energy I state. This exit is slow, on a time scale of seconds, because of activation energy barriers. The trapped misfolded molecules as well as the I molecules contract continuously and slowly as structure develops. A phenomenological model of Markovian evolution of the polymer chain undergoing folding, incorporating these features, has been developed, which fits well the experimentally observed time evolution of distance distributions. The observation that the "wrong turn" to the misfolded state has not been eliminated by evolution belies the common belief that the folding of functional protein sequences is very different from that of a random heteropolymer, and the former have been selected by evolution to fold quickly.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.07.024}, author = {Bhatia, Sandhya and Krishnamoorthy, G and Dhar, Deepak and Udgaonkar, Jayant B} } @article {53182, title = {PASS2 version 6: a database of structure-based sequence alignments of protein domain superfamilies in accordance with SCOPe.}, journal = {Database (Oxford)}, volume = {2019}, year = {2019}, month = {2019 Jan 01}, abstract = {

The number of protein structures is increasing due to the individual initiatives and rapid development of structure determination techniques. Structure-based sequence alignments of distantly related proteins enable the investigation of structural, evolutionary and functional relationships between proteins and their domains leading to their common evolutionary origin. Protein Alignments organized as Structural Superfamilies (PASS2) is a database that provides such alignments of members of protein domain superfamilies of known structure and with less than 40\% sequence identity. PASS2 has been continuously updated in accordance to Structural Classification of Proteins (SCOP), and now Structural Classification of Proteins - extended (SCOPe). The current update directly corresponds to SCOPe 2.06, dealing with 2006 domain superfamilies of known structure and about 14\ 000 domains. Alignments have been augmented by features such as hidden Markov models, highly conserved residues, structural motifs and gene ontology terms, which are available for download. In this update, we introduce the concepts of {\textquoteright}extreme structural outliers{\textquoteright} and {\textquoteright}split superfamilies{\textquoteright} as well.

}, issn = {1758-0463}, doi = {10.1093/database/baz028}, author = {Ghosh, Pritha and Bhattacharyya, Teerna and Mathew, Oommen K and Sowdhamini, Ramanathan} } @article {59711, title = {Pathogen susceptibility and fitness costs explain variation in immune priming across natural populations of flour beetles.}, journal = {J Anim Ecol}, year = {2019}, month = {2019 May 27}, abstract = {

In many insects, individuals primed with low doses of pathogens early in life have higher survival after exposure to the same pathogen later in life. Yet, our understanding of the evolutionary and ecological history of priming of immune response in natural insect populations is limited. Previous work demonstrated population-, sex- and stage-specific variation in the survival benefit of priming response in flour beetles (Tribolium castaneum) infected with their natural pathogen Bacillus thuringiensis. However, the evolutionary forces responsible for this natural variation remained unclear. In the present work, we tested whether the strength of the priming response (measured as the survival benefit after priming and subsequent infection, relative to unprimed controls) was associated with multiple fitness parameters and immune components across 10 flour beetle populations collected from different locations in India. Our results suggest two major selective pressures that may explain the observed inter-population variation in priming: (a) Basal pathogen susceptibility - populations that were more susceptible to infection produced a stronger priming response, and (b) Short-term early reproductive success - populations where primed females produced more offspring early in life (measured over 2\ days) had lower survival benefit (measured over 120\ days), suggesting a potential trade-off between early reproduction and priming response. However, the negative association between survival and reproduction is limited to priming and infection in adults, but not in larvae. While other components of beetle fitness (starvation resistance and larval development) and immune function (haemolymph antibacterial activity and antimicrobial quinone secretion) also varied widely across populations, none of them was correlated with the variation in priming responses across populations. Our work is the first systematic empirical demonstration of multiple selective pressures that may govern the evolution of immune priming in the wild. We hope that this motivates further experiments to establish the role of pathogen-imposed selection and fitness costs in the evolution of priming in natural insect populations.

}, issn = {1365-2656}, doi = {10.1111/1365-2656.13030}, author = {Khan, Imroze and Prakash, Arun and Agashe, Deepa} } @article {57783, title = {Phosphatidylinositol 5 Phosphate 4-Kinase Regulates Plasma-Membrane PIP Turnover and Insulin Signaling.}, journal = {Cell Rep}, volume = {27}, year = {2019}, month = {2019 May 14}, pages = {1979-1990.e7}, abstract = {

Phosphatidylinositol 3,4,5-trisphosphate (PIP) generation at the plasma membrane is a key event during activation of receptor tyrosine kinases such as the insulin receptor required for normal growth and metabolism. We report that in Drosophila, phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is required to limit PIP levels during insulin receptor activation. Depletion of PIP4K increases the levels of PIP produced in response to insulin stimulation. We find that PIP4K function at the plasma membrane enhances class I phosphoinositide 3-kinase (PI3K) activity, although the catalytic ability of PIP4K to produce phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] at the plasma membrane is dispensable for this regulation. Animals lacking PIP4K show enhanced insulin signaling-dependent phenotypes and are resistant to the metabolic consequences of a high-sugar diet, highlighting the importance of PIP4K in normal metabolism and development. Thus, PIP4Ks are key regulators of receptor tyrosine kinase signaling with implications for growth factor-dependent processes including tumor growth, T\ cell activation, and metabolism.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2019.04.084}, author = {Sharma, Sanjeev and Mathre, Swarna and Ramya, Visvanathan and Shinde, Dhananjay and Raghu, Padinjat} } @article {64325, title = {Phosphoinositides: Regulators of Nervous System Function in Health and Disease}, journal = {FRONTIERS IN MOLECULAR NEUROSCIENCE}, volume = {12 }, year = {2019}, month = {08/2019}, abstract = {

Phosphoinositides, the seven phosphorylated derivatives of phosphatidylinositol have emerged as regulators of key sub-cellular processes such as membrane transport, cytoskeletal function and plasma membrane signaling in eukaryotic cells. All of these processes are also present in the cells that constitute the nervous system of animals and in this setting too, these are likely to tune key aspects of cell biology in relation to the unique structure and function of neurons. Phosphoinositides metabolism and function are mediated by enzymes and proteins that are conserved in evolution, and analysis of knockouts of these in animal models implicate this signaling system in neural function. Most recently, with the advent of human genome analysis, mutations in genes encoding components of the phosphoinositide signaling pathway have been implicated in human diseases although the cell biological basis of disease phenotypes in many cases remains unclear. In this review we evaluate existing evidence for the involvement of phosphoinositide signaling in human nervous system diseases and discuss ways of enhancing our understanding of the role of this pathway in the human nervous system{\textquoteright}s function in health and disease.

}, doi = {10.3389/fnmol.2019.00208}, author = {Padinjat, Raghu and Joseph, A and Krishnan, H and Singh, P and Saha, S} } @article {66089, title = {Phosphorylation of Nephrin induces phase separated domains that move through actomyosin contraction.}, journal = {Mol Biol Cell}, year = {2019}, month = {2019 Oct 10}, pages = {mbcE18120823}, abstract = {

The plasma membrane of eukaryotic cells is organized into lipid and protein microdomains, whose assembly mechanisms and functions are incompletely understood. We demonstrate that proteins in the Nephrin/Nck/N-WASP actin-regulatory pathway cluster into micron-scale domains at the basal plasma membrane upon triggered phosphorylation of transmembrane Nephrin. The domains are persistent but readily exchange components with their surroundings, and their formation is dependent on the number of Nck SH3 domains, suggesting they are phase separated polymers assembled through multivalent interactions among the three proteins. The domains form independent of the actin cytoskeleton, but acto-myosin contractility induces their rapid lateral movement. Nephrin phosphorylation induces larger clusters at the cell periphery, which are associated with extensive actin assembly and dense filopodia. Our studies illustrate how multivalent interactions between proteins at the plasma membrane can produce micron-scale organization of signaling molecules, and how the resulting clusters can both respond to and control the actin cytoskeleton. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

}, issn = {1939-4586}, doi = {10.1091/mbc.E18-12-0823}, author = {Kim, Soyeon and Kalappurakkal, Joseph M and Mayor, Satyajit and Rosen, Michael K} } @article {70224, title = { Phylogeny and biogeography of the endemic Hemidactylus geckos of the Indian subregion suggest multiple dispersals from Peninsular India to Sri Lanka}, journal = {Zoological Journal of the Linnean Society}, volume = {186}, year = {2019}, pages = {286{\textendash}301}, abstract = {

Factors shaping biotic assembly of an island compared with the mainland are of considerable interest in biogeography, and the island of Sri Lanka and mainland India provide an interesting setting in which to study this process. We tested two contrasting hypotheses, faunal exchange vs. in situ diversification, to explain how the biota of Sri Lanka might have assembled. We studied the radiation of Hemidactylus geckos, endemic to India and Sri Lanka, to understand the biogeographical processes underlying the faunal assembly of Sri Lanka. We performed molecular phylogenetic analysis, divergence data estimation and ancestral area reconstruction. Diversification in this radiation began ~34.5 Mya in India, followed by seven independent dispersal events from India to Sri Lanka. Two dispersal events occurred in the Early to Middle Miocene, leading to two endemic Sri Lankan species. Marine transgression events separating the two landmasses are likely to have led to vicariant speciation in these cases. The other five dispersal events led to range expansion in species largely restricted to open semi-arid habitats and were likely to be more recent. These results indicate that the biotic exchange model better explains the assembly of Sri Lankan Hemidactylus geckos.

}, doi = {10.1093/zoolinnean/zly047}, author = {Lajmi, Aparna and Bansal, Rohini and Giri, Varad B and Karanth, Praveen} } @article {62761, title = {Plant Antiviral Immunity Against Geminiviruses and Viral Counter-Defense for Survival.}, journal = {Front Microbiol}, volume = {10}, year = {2019}, month = {2019}, pages = {1460}, abstract = {

The family includes plant-infecting viruses whose genomes are composed of one or two circular non-enveloped ssDNAs(+) of about 2.5-5.2 kb each in size. These insect-transmissible geminiviruses cause significant crop losses across continents and pose a serious threat to food security. Under the control of promoters generally located within the intergenic region, their genomes encode five to eight ORFs from overlapping viral transcripts. Most proteins encoded by geminiviruses perform multiple functions, such as suppressing defense responses, hijacking ubiquitin-proteasomal pathways, altering hormonal responses, manipulating cell cycle regulation, and exploiting protein-signaling cascades. Geminiviruses establish complex but coordinated interactions with several host elements to spread and facilitate successful infection cycles. Consequently, plants have evolved several multilayered defense strategies against geminivirus infection and distribution. Recent studies on the evasion of host-mediated resistance factors by various geminivirus proteins through novel mechanisms have provided new insights into the development of antiviral strategies against geminiviruses. This review summarizes the current knowledge concerning virus movement within and between cells, as well as the recent advances in our understanding of the biological roles of virus-encoded proteins in manipulating host-mediated responses and insect transmission. This review also highlights unexplored areas that may increase our understanding of the biology of geminiviruses and how to combat these important plant pathogens.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2019.01460}, author = {Kumar, R Vinoth} } @article {62754, title = {Plant Volatiles Modulate Immune Responses of Spodoptera litura.}, journal = {J Chem Ecol}, year = {2019}, month = {2019 Aug 06}, abstract = {

Plants emit a specific blend of volatiles in response to herbivory and these volatiles, which often attract predators and parasitoids function as an indirect plant defense. The impact of plant volatiles in shaping herbivore defenses is unclear. Here, we report that specific plant volatiles induce immune responses in the polyphagous herbivore, Spodoptera litura. We characterized the hemocyte profile and established their functional significance with respect to ontogeny and exposure to specific plant volatiles. Fifth instar larvae showed the highest number and hemocytes diversity. We characterized seven different types of hemocytes, of which granulocytes performed phagocytosis, oenocytoids showed melanization activity, and plasmatocytes along with granulocytes and oenocytoids were found to be involved in encapsulation. Among the six volatiles tested, exposure to (E)-β-ocimene caused the highest increase in total hemocytes number (THC) followed by linalool and (Z)-3-hexenyl acetate exposure. Although THC did not differ between these three volatile treatments, circulating hemocytes diversity varied significantly. (E)-β-ocimene exposure showed higher number of plasmatocytes and phenol oxidase activity. The interaction of the parasitic wasp Bracon brevicornis with (E)-β-ocimene exposed larvae was poor in terms of delayed paralysis and lower egg deposition. In choice assays, the wasp showed clear preference towards control larvae indicating (E)-β-ocimene treatment renders the host unattractive. Hemocyte profiles post-parasitoid exposure and (E)-β-ocimene treatment were similar indicating cue-based priming. When challenged with Bacillus thuringiensis, linalool exposure resulted in the highest survival as compared to other volatiles. Our results show that specific HIPVs can modulate cellular immunity of S. litura, revealing a new role for HIPVs in tri-trophic interactions.

}, issn = {1573-1561}, doi = {10.1007/s10886-019-01091-3}, author = {Ghosh, Enakshi and Venkatesan, Radhika} } @article {65306, title = {A polar filter in DNA polymerases prevents ribonucleotide incorporation.}, journal = {Nucleic Acids Res}, year = {2019}, month = {2019 Sep 23}, abstract = {

The presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality. To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) possess a steric filter. The dPol named MsDpo4 (Mycobacterium smegmatis) naturally lacks this steric filter and hence is capable of rNTP addition. The introduction of the steric filter in MsDpo4 did not result in complete abrogation of the ability of this enzyme to incorporate ribonucleotides. In comparison, DNA polymerase IV (PolIV) from Escherichia coli exhibited stringent selection for deoxyribonucleotides. A comparison of MsDpo4 and PolIV led to the discovery of an additional polar filter responsible for sugar selectivity. Thr43 represents the filter in PolIV and this residue forms interactions with the incoming nucleotide to draw it closer to the enzyme surface. As a result, the 2{\textquoteright}-OH in rNTPs will clash with the enzyme surface, and therefore ribonucleotides cannot be accommodated in the active site in a conformation compatible with productive catalysis. The substitution of the equivalent residue in MsDpo4-Cys47, with Thr led to a drastic reduction in the ability of the mycobacterial enzyme to incorporate rNTPs. Overall, our studies evince that the polar filter serves to prevent ribonucleotide incorporation by dPols.

}, issn = {1362-4962}, doi = {10.1093/nar/gkz792}, author = {Johnson, Mary K and Kottur, Jithesh and Nair, Deepak T} } @article {56659, title = {Precise excitation-inhibition balance controls gain and timing in the hippocampus.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Apr 25}, abstract = {

Excitation-inhibition (EI) balance controls excitability, dynamic range, and input gating in many brain circuits. Subsets of synaptic input can be selected or {\textquoteright}gated{\textquoteright} by precise modulation of finely tuned EI balance, but assessing the granularity of EI balance requires combinatorial analysis of excitatory and inhibitory inputs. Using patterned optogenetic stimulation of mouse hippocampal CA3 neurons, we show that hundreds of unique CA3 input combinations recruit excitation and inhibition with a nearly identical ratio, demonstrating precise EI balance at the hippocampus. Crucially, the delay between excitation and inhibition decreases as excitatory input increases from a few synapses to tens of synapses. This creates a dynamic millisecond-range window for postsynaptic excitation, controlling membrane depolarization amplitude and timing via subthreshold divisive normalization. We suggest that this combination of precise EI balance and dynamic EI delays forms a general mechanism for millisecond-range input gating and subthreshold gain control in feedforward networks.

}, issn = {2050-084X}, doi = {10.7554/eLife.43415}, author = {Bhatia, Aanchal and Moza, Sahil and Bhalla, Upinder Singh} } @article {60612, title = {Predictability in the evolution of Orthopteran cardenolide insensitivity.}, journal = {Philos Trans R Soc Lond B Biol Sci}, volume = {374}, year = {2019}, month = {2019 Jul 22}, pages = {20180246}, abstract = {

The repeated evolutionary specialization of distantly related insects to cardenolide-containing host plants provides a stunning example of parallel adaptation. Hundreds of herbivorous insect species have independently evolved insensitivity to cardenolides, which are potent inhibitors of the alpha-subunit of Na,K-ATPase (ATPα). Previous studies investigating ATPα-mediated cardenolide insensitivity in five insect orders have revealed remarkably high levels of parallelism in the evolution of this trait, including the frequent occurrence of parallel amino acid substitutions at two sites and recurrent episodes of duplication followed by neo-functionalization. Here we add data for a sixth insect order, Orthoptera, which includes an ancient group of highly aposematic cardenolide-sequestering grasshoppers in the family Pyrgomorphidae. We find that Orthopterans exhibit largely predictable patterns of evolution of insensitivity established by sampling other insect orders. Taken together the data lend further support to the proposal that negative pleiotropic constraints are a key determinant in the evolution of cardenolide insensitivity in insects. Furthermore, analysis of our expanded taxonomic survey implicates positive selection acting on site 111 of cardenolide-sequestering species with a single-copy of ATPα, and sites 115, 118 and 122 in lineages with neo-functionalized duplicate copies, all of which are sites of frequent parallel amino acid substitution. This article is part of the theme issue {\textquoteright}Convergent evolution in the genomics era: new insights and directions{\textquoteright}.

}, issn = {1471-2970}, doi = {10.1098/rstb.2018.0246}, author = {Yang, Lu and Ravikanthachari, Nitin and Mari{\~n}o-P{\'e}rez, Ricardo and Deshmukh, Riddhi and Wu, Mariana and Rosenstein, Adam and Kunte, Krushnamegh and Song, Hojun and Andolfatto, Peter} } @article {66849, title = {Protected areas and biodiversity conservation in India}, journal = {BIOLOGICAL CONSERVATION}, volume = {237}, year = {2019}, month = {09/2019}, pages = {114-124}, abstract = {

Three well-supported generalizations in conservation biology are that developing tropical countries will experience the greatest biodiversity declines in the near future, they are some of the least studied areas in the world, and in these regions especially, protection requires local community support. We assess these generalizations in an evaluation of protected areas in India. The 5\% of India officially protected covers most ecoregions and protected areas have been an important reason why India has suffered no documented species extinctions in the past 70 years. India has strong legislation favouring conservation, government investment focused on 50 Tiger Reserves, and government compensation schemes that facilitate local support, all of which brighten future prospects. However, many protected areas are too small to maintain a full complement of species, making connectivity and species use of buffer zones a crucial issue. Conservation success and challenges vary across regions according to their development status. In less developed areas, notably the biodiverse northeast Himalaya, protected areas maintaining the highest biodiversity result from locally-focused efforts by dedicated individuals. Across India, we demonstrate considerable opportunities to increase local income through ecotourism. Our evaluation confirms a lack of data, increasing threats, and the importance of local support. Research on biodiversity in buffer zones, development of long-term monitoring schemes, and assessment of cash and conservation benefits from tourism are in particular need. For policy makers, two main goals should be the development of monitoring plans for {\textquoteleft}eco-sensitive zones{\textquoteright} around protected areas, and a strong emphasis on preserving established protected areas.

}, doi = {10.1016/j.biocon.2019.06.024}, author = {Ghosh-Harihar, M and An, R and Athrey, R and Borthakur, U and Chanchani, P and Chetry, D and Datta, A and Harihar, A and Karanth, KK and Mariyam, D and Mohan, D and Onial, M and Ramakrishnan, U and Robin, VV and Saxena, A and Shahabuddin, G and Thatte, P and Vijay, V and Wacker, K and Mathur, VB and Pimm, SL and Price, TD} } @article {53189, title = {Recent advances in clathrin-independent endocytosis.}, journal = {F1000Res}, volume = {8}, year = {2019}, month = {2019}, abstract = {

Endocytic pathways are broadly classified into clathrin dependent and independent on the basis of the requirement for the coat protein, clathrin. The molecular pathways and mechanisms underlying the formation of clathrin-independent pathways are still being explored, and this review summarizes recent advances and emerging functional roles of these diverse pathways. In particular, this review will discuss the growing consensus on the role of BAR domain proteins and the actin machinery in different clathrin-independent pathways and its significance to the functions fulfilled by these endocytic pathways.

}, issn = {2046-1402}, doi = {10.12688/f1000research.16549.1}, author = {Hemalatha, Anupama and Mayor, Satyajit} } @article {56653, title = {Rediscovery of Cnemaspis nilagirica Manamendra-Arachchi, Batuwita and Pethiyagoda, 2007 (Squamata: Gekkonidae) from Kerala, India with notes on morphology and distribution}, journal = {ZOOTAXA}, volume = {4586}, year = {2019}, month = {04/2019}, pages = {98-108}, abstract = {

Cnemaspis nilagirica was described by Manamendra-Arachchi, Batuwita and Pethiyagoda in 2007 based on a single female specimen that was a syntype of Gonatodes kandianus var. tropidogaster described by Boulenger in 1885. However, a living population of this species has not been reported since its original description by Boulenger. Based on fresh material and comparisons with the holotype of C. nilagirica, we here report the collection of this species after over 130 years. We provide the first description of a male specimen and additional information on morphological variation, distribution and natural history.

}, doi = {10.11646/zootaxa.4586.1.4}, author = {Cyriac, VP and Johny, Alex and Umesh, P and Palot, M and Campbell, PD} } @article {60328, title = {Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications.}, journal = {Front Cell Dev Biol}, volume = {7}, year = {2019}, month = {2019}, pages = {83}, abstract = {

Phosphatidic acid (PA) is a simple glycerophospholipid with a well-established role as an intermediate in phospholipid biosynthesis. In addition to its role in lipid biosynthesis, PA has been proposed to act as a signaling molecule that modulates several aspects of cell biology including membrane transport. PA can be generated in eukaryotic cells by several enzymes whose activity is regulated in the context of signal transduction and enzymes that can metabolize PA thus terminating its signaling activity have also been described. Further, several studies have identified PA binding proteins and changes in their activity are proposed to be mediators of the signaling activity of this lipid. Together these enzymes and proteins constitute a PA signaling toolkit that mediates the signaling functions of PA in cells. Recently, a number of novel genetic models for the analysis of PA function and analytical methods to quantify PA levels in cells have been developed and promise to enhance our understanding of PA functions. Studies of several elements of the PA signaling toolkit in a single cell type have been performed and are presented to provide a perspective on our understanding of the biochemical and functional organization of pools of PA in a eukaryotic cell. Finally, we also provide a perspective on the potential role of PA in human disease, synthesizing studies from model organisms, human disease genetics and analysis using recently developed PLD inhibitors.

}, issn = {2296-634X}, doi = {10.3389/fcell.2019.00083}, author = {Thakur, Rajan and Naik, Amruta and Panda, Aniruddha and Raghu, Padinjat} } @article {56127, title = {Response of grassland ecosystem to monsoonal precipitation variability during the Mid-Late Holocene: Inferences based on molecular isotopic records from Banni grassland, western India.}, journal = {PLoS One}, volume = {14}, year = {2019}, month = {2019}, pages = {e0212743}, abstract = {

Banni, located in the arid western India, is one of the largest tropical grasslands of the Asian continent. The net primary production in this grassland ecosystem is currently mediated by precipitation during the Indian summer monsoon (ISM). However, timing of the grassland expansion and its link to the intensity of monsoonal precipitation remains enigmatic due to the paucity of datasets. The major objective of this study is to understand the changes in monsoonal precipitation and vegetation for the last 4600 cal yr BP using hydrogen and carbon isotopic composition of n-alkanes (δDn-alkane and δ13Cn-alkane) measured from two core sediments (Chachi and Luna) in Banni region. The δ13CC29 and δ13CC31 values for Chachi core sediments vary from -30.9 {\textperthousand} to -27.2 {\textperthousand} and -34.4 {\textperthousand} to -25 {\textperthousand} respectively. The δ13Cn-alkane values from the core sediments are converted into \%C4 plants based on a binary mixing model using the end-member δ13Cn-alkane values derived from the dominant modern vegetation in the Banni region. The prominent feature of the paleovegetation curve is the marked increase in the δ13Cn-alkane values after 2500 cal yr BP, which suggests proliferation of C4 grasses in this region. Similar changes after 2500 cal yr BP have also been observed in the δDn-alkane values. The δDC29 values are used to calculate δD value of paleoprecipitation that varied from 10 {\textperthousand} to -60.2 {\textperthousand}. A significant increase in the δD values of paleoprecipitation (ca. 25 {\textperthousand}) indicates a weakened ISM precipitation after ca. 2500 cal yr BP. The regional aridification and frequent fire events may have helped the expansion of C4 plant dominated grassland ecosystem in Banni region. Correlation between paleoclimatic records suggests that the southward migration of intertropical convergence zone and more frequent warm phases of El-Nino Southern Oscillation have triggered the weakening of monsoonal precipitation in the tropical region.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0212743}, author = {Basu, Sayak and Sanyal, Prasanta and Pillai, Anusree A S and Ambili, Anoop} } @article {62758, title = {RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target.}, journal = {J Exp Clin Cancer Res}, volume = {38}, year = {2019}, month = {2019 Jul 24}, pages = {328}, abstract = {

Tumor heterogeneity results in differential response to therapy due to the existence of plastic tumor cells, called cancer stem cells (CSCs), which exhibit the property of resistance to therapy, invasion and metastasis. These cells have a distinct, signaling network active at every stage of progression. It is difficult to envisage that the CSCs will have a unique set of signaling pathways regulating every stage of disease progression. Rather, it would be easier to believe that a single pivotal pathway having significant contribution at every stage, which can further turn on a battery of signaling mechanisms specific to that stage, would be instrumental in regulating the signaling network, enabling easy transition from one state to another. In this context, we discuss the role of RhoC which has contributed to several phenotypes during tumor progression.RhoC (Ras homolog gene family member C) has been widely reported to regulate actin organization. It has been shown to impact the motility of cancer cells, resultantly affecting invasion and metastasis, and has contributed to carcinoma progression of the breast, pancreas, lung, ovaries and cervix, among several others. The most interesting finding has been its indispensable role in metastasis. Also, it has the ability to modulate various other phenotypes like angiogenesis, motility, invasion, metastasis, and anoikis resistance. These observations suggest that RhoC imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. Studies also suggest that the inhibition of RhoC results in abolition of advanced tumor phenotypes.Our review throws light on how RhoC, which is capable of modulating various phenotypes may be the apt core signaling candidate regulating disease progression. Additionally, mice studies show that RhoC is not essential for embryogenesis, giving scope for its development as a possible therapeutic target. This review thus stresses on the need to understand the protein and its functioning in greater detail to enable its development as a stem cell marker and a possible therapeutic target.

}, issn = {1756-9966}, doi = {10.1186/s13046-019-1327-4}, author = {Thomas, Pavana and Pranatharthi, Annapurna and Ross, Cecil and Srivastava, Sweta} } @article {64329, title = {RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer.}, journal = {J Exp Clin Cancer Res}, volume = {38}, year = {2019}, month = {2019 Sep 05}, pages = {392}, abstract = {

BACKGROUND: Radioresistance remains a challenge to the successful treatment of various tumors. Intrinsic factors like alterations in signaling pathways regulate response to radiation. RhoC, which has been shown to modulate several tumor phenotypes has been investigated in this report for its role in radioresistance. In vitro and clinical sample-based studies have been performed to understand its contribution to radiation response in cervical cancer and this is the first report to establish the role of RhoC and its effector ROCK2 in cervical cancer radiation response.

METHODS: Biochemical, transcriptomic and immunological approaches including flow cytometry and immunofluorescence were used to understand the role of RhoC and ROCK2. RhoC variants, siRNA and chemical inhibitors were used to alter the function of RhoC and ROCK2. Transcriptomic profiling was performed to understand the gene expression pattern of the cells. Live sorting using an intracellular antigen has been developed to isolate the cells for transcriptomic studies.

RESULTS: Enhanced expression of RhoC conferred radioprotection on the tumor cells while inhibition of RhoC resulted in sensitization of cells to radiation. The RhoC overexpressing cells had a better DNA repair machinery as observed using transcriptomic analysis. Similarly, overexpression of ROCK2, protected tumor cells against radiation while its inhibition increased radiosensitivity in vitro. Further investigations revealed that ROCK2 inhibition abolished the radioresistance phenotype, conferred by RhoC on SiHa cells, confirming that it is a downstream effector of RhoC in this context. Additionally, transcriptional analysis of the live sorted ROCK2 high and ROCK2 low expressing SiHa cells revealed an upregulation of the DNA repair pathway proteins. Consequently, inhibition of ROCK2 resulted in reduced expression of pH2Ax and MRN complex proteins, critical to repair of double strand breaks. Clinical sample-based studies also demonstrated that ROCK2 inhibition sensitizes tumor cells to irradiation.

CONCLUSIONS: Our data primarily indicates that RhoC and ROCK2 signaling is important for the radioresistance phenotype in cervical cancer tumor cells and is regulated via association of ROCK2 with the proteins of DNA repair pathway involving pH2Ax, MRE11 and RAD50 proteins, partly offering insights into the mechanism of radioresistance in tumor cells. These findings highlight RhoC-ROCK2 signaling involvement in DNA repair and urge the need for development of these molecules as targets to alleviate the non-responsiveness of cervical cancer tumor cells to irradiation treatment.

}, issn = {1756-9966}, doi = {10.1186/s13046-019-1385-7}, author = {Pranatharthi, Annapurna and Thomas, Pavana and Udayashankar, Avinash H and Bhavani, Chandra and Suresh, Srinag Bangalore and Krishna, Sudhir and Thatte, Jayashree and Srikantia, Nirmala and Ross, Cecil R and Srivastava, Sweta} } @article {56658, title = {Rodent models of social stress and neuronal plasticity: relevance to depressive-like disorders.}, journal = {Behav Brain Res}, year = {2019}, month = {2019 Apr 22}, abstract = {

Exposure to severe or persistent social stress may lead to the development of psychiatric disorders such as anxiety and depression. These mood disorders are associated with structural alterations of neural architecture in limbic brain regions that control emotion, mood and cognition. Structural remodeling may either be a sign of successful adaptation, or of failure to do so. In neuropsychiatric disorders like depression structural remodeling involves apoptosis, reduced neurogenesis, and structural remodeling of neuronal dendrites which most likely reflects the latter. Here we review key findings from animal models of psychosocial stress that have been used to gain insights into the relation between stress-related behavioral disorders like depression and structural plasticity. Specifically, we focus on models having a high face validity like social defeat stress in the resident-intruder paradigm and chronic stress of social subordination in social housing conditions. Moderate to severe social stress appears to stimulate plasticity and neuronal growth in regions of the amygdala, whereas the effects in the hippocampus and prefrontal cortex tend to be opposite. A major focus of the current review is to characterize social stress induced structural changes in these brain regions, aiming to provide insight in pathways and factors that underlie behavioral effects of stress and depression.

}, issn = {1872-7549}, doi = {10.1016/j.bbr.2019.111900}, author = {Patel, Deepika and Kas, Martien J and Chattarji, Sumantra and Buwalda, Bauke} } @article {65304, title = {Root trait variation in African savannas}, journal = {Plant and Soil}, volume = {441}, year = {2019}, month = {08/2019}, pages = {555{\textendash}565}, abstract = {

While patterns of variation in woody plant aboveground traits related to disturbance and resource availability in savanna ecosystems are fairly well understood, dimensions of variation in belowground traits remain poorly understood. We investigate how sapling coarse root (\>2\ mm diameter) traits and belowground storage organs vary with respect to differing disturbance regimes (i.e. fire or herbivore dominated) and soil fertility in Southern African savannas.

}, doi = {10.1007/s11104-019-04145-3}, author = {Wigley, BJ and Staver, C and Zytkowiak, R and Jagodzinski, AM and Wigley-Coetsee, C} } @article {49278, title = {Ruggedness in the Free Energy Landscape Dictates Misfolding of the Prion Protein.}, journal = {J Mol Biol}, year = {2019}, month = {2019 Jan 03}, abstract = {

Experimental determination of the key features of the free energy landscapes of proteins which dictate their adeptness to fold correctly, or propensity to misfold and aggregate, and which are modulated upon a change from physiological to aggregation-prone conditions, is a difficult challenge. In this study, sub-millisecond kinetic measurements of the folding and unfolding of the mouse prion protein (moPrP), reveal how the free energy landscape becomes more complex upon a shift from physiological (pH 7) to aggregation-prone (pH 4) conditions. Folding and unfolding utilize the same single pathway at pH 7, but at pH 4, folding occurs on a pathway distinct from the unfolding pathway. Moreover, the kinetics of both folding and unfolding at pH 4 depend not only on the final conditions, but also on the conditions under which the processes are initiated. Unfolding can be made to switch to occur on the folding pathway by varying the initial conditions. Folding and unfolding pathways appear to occupy different regions of the free energy landscape, which are separated by large free energy barriers that change with a change in the initial conditions. These barriers direct unfolding of the native protein to proceed via an aggregation-prone intermediate previously identified to initiate the misfolding of moPrP at low pH, thus identifying a plausible mechanism by which the ruggedness of the free energy landscape of a protein may modulate its aggregation propensity.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2018.12.009}, author = {Moulick, Roumita and Goluguri, Rama Reddy and Udgaonkar, Jayant B} } @article {62773, title = {Seed Elaiosome Mediates Dispersal by Ants and Impacts Germination in Ricinus communis}, journal = {FRONTIERS IN ECOLOGY AND EVOLUTION}, volume = {7}, year = {2019}, month = {06/2019}, abstract = {

Myrmecochory is the ant-mediated secondary dispersal of seeds that depends on the presence of a lipid-rich seed appendage known as {\textquotedblleft}elaiosome.{\textquotedblright} Attractive cues of elaiosomes that drive such an interaction and benefits to the plant are not clearly understood. Here, using Ricinus communis, we establish reward compositions and determine the benefits of myrmecochory to the plant. We also compare elaiosome compositions across ecotypes. Our results show that the elaiosome is essential for seed displacement and olfactory cues are important attractive cues. Nonanal and 2-decenal were found to be the major attractive volatiles in the castor elaiosome. Different ant species showed different behaviors toward elaiosome-bearing seeds. Among them, Pheidole grayi was efficient in dispersal but did not disperse all seed ecotypes tested. Major differences in fatty acid levels were observed between ecotypes. To determine the benefits of myrmecochory, germination rates before and after removal of elaiosome were studied. Seed germination improved upon elaiosome removal and aqueous elaiosome extract inhibited germination indicating water-soluble inhibitory factors. Further, ant nest sites were richer in nitrogen than control sites, revealing a clear benefit of seed displacement. In summary, we demonstrate the ecological significance of the seed elaiosomes in the absence of nutritive rewards for seed dispersers.

}, doi = {10.3389/fevo.2019.00246}, author = {Sasidharan, R and Venkatesan, Radhika} } @article {62760, title = {Self-Driven Phase Transitions Drive Myxococcus xanthus Fruiting Body Formation.}, journal = {Phys Rev Lett}, volume = {122}, year = {2019}, month = {2019 Jun 21}, pages = {248102}, abstract = {

Combining high-resolution single cell tracking experiments with numerical simulations, we show that starvation-induced fruiting body formation in Myxococcus xanthus is a phase separation driven by cells that tune their motility over time. The phase separation can be understood in terms of cell density and a dimensionless P{\'e}clet number that captures cell motility through speed and reversal frequency. Our work suggests that M. xanthus takes advantage of a self-driven nonequilibrium phase transition that can be controlled at the single cell level.

}, keywords = {Cell Movement, Myxococcus xanthus, Phase Transition}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.122.248102}, author = {Liu, Guannan and Patch, Adam and Bahar, Fatmag{\"u}l and Yllanes, David and Welch, Roy D and Marchetti, M Cristina and Thutupalli, Shashi and Shaevitz, Joshua W} } @article {65299, title = {Serotonin is essential for eye regeneration in planaria Schmidtea mediterranea.}, journal = {FEBS Lett}, year = {2019}, month = {2019 Sep 17}, abstract = {

Planaria is an ideal system to study factors involved in regeneration and tissue homeostasis. Little is known about the role of metabolites and small molecules in stem cell maintenance and lineage specification in planarians. Using liquid chromatography and mass spectrometry (LC-MS)-based quantitative metabolomics, we determined the relative levels of metabolites in stem cells, progenitors, and differentiated cells of the planarian Schmidtea mediterranea. Tryptophan and its metabolic product serotonin are significantly enriched in stem cells and progenitor population. Serotonin biosynthesis in these cells is brought about by a non-canonical enzyme, phenylalanine hydroxylase (PAH). Knockdown of Smed-pah leads to complete disappearance of eyes in regenerating planaria, while exogenous supply of serotonin and its precursor rescue the eyeless phenotype. Our results demonstrate a key role for serotonin in eye regeneration.

}, issn = {1873-3468}, doi = {10.1002/1873-3468.13607}, author = {Sarkar, Arunabha and Mukundan, Namita and Sowndarya, Sai and Dubey, Vinay Kumar and Babu, Rosana and Lakshmanan, Vairavan and Rangiah, Kannan and Panicker, Mitradas M and Palakodeti, Dasaradhi and Subramanian, Sabarinath Peruvemba and Ramaswamy, Subramanian} } @article {54878, title = {Size{\textendash}logging interactions and population dynamics in tropical understorey birds}, journal = {Current Science}, volume = {116}, year = {2019}, month = {03/2019}, pages = {795-801}, abstract = {

Demographic vital rates (e.g., fecundity and survival) determine population size and viability. However, how anthropogenic habitat change differentially influences these dynamic population processes for species with different traits remains unknown. Crucially, this limits a mechanistic understanding of species- and commu-nity-level patterns in response to intensity of habitat change, and therefore, impedes robust prediction of future species responses. We investigated how size (across 26 forest birds, spanning almost an order of magnitude in body mass) and habitat modification (logging intensity, from intact forest to a 2.5-fold re-duction in tree density) might interact to influence survival, reproduction and dispersal. Data were col-lected over five sessions under the robust design in a capture-mark-recapture framework and analysed using reverse time capture{\textendash}recapture models. We found that smaller species were more fecund with in-creased logging intensity, and dispersed from more heavily logged to more intact forest. With increasing size, species reproduced better in progressively more intact forest, and dispersed from intact forest into more logged forest. These results indicate important trait-linked differences in the relative significance of various demographic processes in influencing species responses to varying intensities of habitat change. Separating the mechanistic processes underlying observed patterns is crucial to understanding and predicting anthropogenic impacts on biodiversity.

}, url = {https://www.currentscience.ac.in/php/toc.php?vol=116\&issue=05}, author = {Srinivasan, U and Quader, Suhel} } @article {65300, title = {Small protein-protein interfaces rich in electrostatic are often linked to regulatory function.}, journal = {J Biomol Struct Dyn}, year = {2019}, month = {2019 Sep 09}, pages = {1-20}, abstract = {

Protein-protein interaction (PPI) is critical for several biological functions in living cells through the formation of an interface. Therefore, it is of interest to characterize protein-protein interfaces using an updated non-redundant structural dataset of 2557 homo (identical subunits) and 393 hetero (different subunits) dimer protein complexes determined by X-ray crystallography. We analyzed the interfaces using van der Waals (vdW), hydrogen bonding and electrostatic energies. Results show that on average homo and hetero interfaces are similar. Hence, we further grouped the 2950 interfaces based on percentage vdW to total energies into dominant (>=60\%) and sub-dominant (\<60\%) vdW interfaces. Majority (92\%) of interfaces have dominant vdW energy with large interface size (146 {\textpm} 87 (homo) and 137 {\textpm} 76 (hetero) residues) and interface area (1622 {\textpm} 1135 {\r A} (homo) and 1579 {\textpm} 1060 {\r A} (hetero)). However, a proportion (8\%) of interfaces have sub-dominant vdW energy with small interface size (85 {\textpm} 46 (homo) and 88 {\textpm} 36 (hetero) residues) and interface area (823 {\textpm} 538 {\r A} (homo) and 881 {\textpm} 377 {\r A} (hetero)). It is found that large interfaces have two-fold more interface area and interface size than small interfaces with increasing hydrogen bonding energy to interface size. However, small interfaces have three-fold more electrostatics energy than large interfaces with increasing electrostatics to interface size. Thus, 8\% of complexes having small interfaces with limited interface area and sub-dominant vdW energy are rich in electrostatics. It is interesting to observe that complexes having small interfaces are often associated with regulatory function. Hence, the observed structural features with known molecular function provide insights for the better understanding of PPI. Communicated by Ramaswamy H. Sarma.

}, issn = {1538-0254}, doi = {10.1080/07391102.2019.1657040}, author = {Nilofer, Christina and Sukhwal, Anshul and Mohanapriya, Arumugam and Sakharkar, Meena Kishore and Kangueane, Pandjassarame} } @article {53617, title = {Social modulation of individual differences in dance communication in honey bees}, journal = {Behavioral Ecology and Sociobiology}, volume = {74}, year = {2019}, month = {04/2019}, chapter = {41}, abstract = {

Group-living animals must constantly integrate and respond to information from other individuals within the group. The degree to which consistent inter-individual behavioural differences are influenced by social cues in such groups is largely unanswered. We used the honey bee waggle dance as an experimental paradigm to explore this question. Honey bee foragers use the waggle dance behaviour to communicate information about food sources in the environment to their nest mates. This recruitment process incorporates information about the food reward, the colony food stores and the environmental food availability and plays a major role in ensuring efficient exploitation of the food sources available to the colony. We first observed individual foragers visiting the same food source and quantified the probability and intensity of their dance activity. We found that there are consistent inter-individual differences in both measures of dance activity within a forager group. Next, we removed foragers and observed that this led to a significant increase in the average dance activity of some foragers. The individuals which increased their dance activity were the ones which were more active before the removal. Finally, we allowed recruits to join the foragers at the food source, which had a strong inhibitory effect on the dance activity of all the individual foragers. Our study shows that a complex interplay between individual behavioural differences and social interactions drives the dance communication needed to effectively organise the colony{\textquoteright}s collective foraging behaviour.

}, doi = {10.1007/s00265-019-2649-0}, author = {George, EA and Brockmann, Axel} } @article {62916, title = {Social-environmental drivers inform strategic management of coral reefs in the Anthropocene.}, journal = {Nat Ecol Evol}, year = {2019}, month = {2019 Aug 12}, abstract = {

Without drastic efforts to reduce carbon emissions and mitigate globalized stressors, tropical coral reefs are in jeopardy. Strategic conservation and management requires identification of the environmental and socioeconomic factors driving the persistence of scleractinian coral assemblages-the foundation species of coral reef ecosystems. Here, we compiled coral abundance data from 2,584 Indo-Pacific reefs to evaluate the influence of 21 climate, social and environmental drivers on the ecology of reef coral assemblages. Higher abundances of framework-building corals were typically associated with: weaker thermal disturbances and longer intervals for potential recovery; slower human population growth; reduced access by human settlements and markets; and less nearby agriculture. We therefore propose a framework of three management strategies (protect, recover or transform) by considering: (1) if reefs were above or below a proposed threshold of \>10\% cover of the coral taxa important for structural complexity and carbonate production; and (2) reef exposure to severe thermal stress during the 2014-2017 global coral bleaching event. Our findings can guide urgent management efforts for coral reefs, by identifying key threats across multiple scales and strategic policy priorities that might sustain a network of functioning reefs in the Indo-Pacific to avoid ecosystem collapse.

}, issn = {2397-334X}, doi = {10.1038/s41559-019-0953-8}, author = {Darling, Emily S and McClanahan, Tim R and Maina, Joseph and Gurney, Georgina G and Graham, Nicholas A J and Januchowski-Hartley, Fraser and Cinner, Joshua E and Mora, Camilo and Hicks, Christina C and Maire, Eva and Puotinen, Marji and Skirving, William J and Adjeroud, Mehdi and Ahmadia, Gabby and Arthur, Rohan and Bauman, Andrew G and Beger, Maria and Berumen, Michael L and Bigot, Lionel and Bouwmeester, Jessica and Brenier, Ambroise and Bridge, Tom C L and Brown, Eric and Campbell, Stuart J and Cannon, Sara and Cauvin, Bruce and Chen, Chaolun Allen and Claudet, Joachim and Denis, Vianney and Donner, Simon and Fadli, Nur and Feary, David A and Fenner, Douglas and Fox, Helen and Franklin, Erik C and Friedlander, Alan and Gilmour, James and Goiran, Claire and Guest, James and Hobbs, Jean-Paul A and Hoey, Andrew S and Houk, Peter and Johnson, Steven and Jupiter, Stacy D and Kayal, Mohsen and Kuo, Chao-Yang and Lamb, Joleah and Lee, Michelle A C and Low, Jeffrey and Muthiga, Nyawira and Muttaqin, Efin and Nand, Yashika and Nash, Kirsty L and Nedlic, Osamu and Pandolfi, John M and Pardede, Shinta and Patankar, Vardhan and Penin, Lucie and Ribas-Deulofeu, Lauriane and Richards, Zoe and Roberts, T Edward and Rodgers, Ku{\textquoteright}ulei S and Safuan, Che Din Mohd and Sala, Enric and Shedrawi, George and Sin, Tsai Min and Smallhorn-West, Patrick and Smith, Jennifer E and Sommer, Brigitte and Steinberg, Peter D and Sutthacheep, Makamas and Tan, Chun Hong James and Williams, Gareth J and Wilson, Shaun and Yeemin, Thamasak and Bruno, John F and Fortin, Marie-Jos{\'e}e and Krkosek, Martin and Mouillot, David} } @article {67829, title = {Soil net nitrogen mineralisation across global grasslands.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Oct 31}, pages = {4981}, abstract = {

Soil nitrogen mineralisation (N), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net N) varies with soil properties and climate. However, because most global-scale assessments of net N are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net N across 30 grasslands worldwide. We find that realised N is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential N only weakly correlates with realised N, but contributes to explain realised net N when combined with soil and climatic variables. We provide novel insights of global realised soil net N and show that potential soil net N data available in the literature could be parameterised with soil and climate data to better predict realised N.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-12948-2}, author = {Risch, A C and Zimmermann, S and Ochoa-Hueso, R and Sch{\"u}tz, M and Frey, B and Firn, J L and Fay, P A and Hagedorn, F and Borer, E T and Seabloom, E W and Harpole, W S and Knops, J M H and McCulley, R L and Broadbent, A A D and Stevens, C J and Silveira, M L and Adler, P B and B{\'a}ez, S and Biederman, L A and Blair, J M and Brown, C S and Caldeira, M C and Collins, S L and Daleo, P and di Virgilio, A and Ebeling, A and Eisenhauer, N and Esch, E and Eskelinen, A and Hagenah, N and Hautier, Y and Kirkman, K P and MacDougall, A S and Moore, J L and Power, S A and Prober, S M and Roscher, C and Sankaran, M and Siebert, J and Speziale, K L and Tognetti, P M and Virtanen, R and Yahdjian, L and Moser, B} } @article {69321, title = {Soil respiration in a tropical montane grassland ecosystem is largely heterotroph-driven and increases under simulated warming}, journal = {Agricultural and Forest Meteorology}, volume = {276-277}, year = {2019}, month = {10/2019}, abstract = {

Soil respiration, a major source of atmospheric carbon (C), can feed into climate warming, which in turn can amplify soil CO2 efflux by affecting respiration by plant roots, arbuscular mycorrhizal fungi (AMF) and other heterotrophic organisms. Although tropical ecosystems contribute \>60\% of the global soil CO2 efflux, there is currently a dearth of data on tropical soil respiration responses to increasing temperature. Here we report a simulated warming and soil respiration partitioning experiment in tropical montane grasslands in the Western Ghats in southern India. The study aimed to (a) evaluate soil respiration responses to warming, (b) assess the relative contributions of autotrophic and heterotrophic components to soil respiration, and (c) assess the roles of soil temperature and soil moisture in influencing soil respiration in this system. Soil respiration was tightly coupled with instantaneous soil moisture availability in both the warmed and control plots, with CO2 efflux levels peaking during the wet season. Soil warming by \~{}1.4 {\textdegree}C nearly doubled soil respiration from 0.62 g CO2 m-2 hr-1 under ambient conditions to 1.16 g CO2 m-2 hr-1 under warmed conditions. Warming effects on soil CO2 efflux were dependent on water availability, with greater relative increases in soil respiration observed under conditions of low (with a minimum of 2.6\%), compared to high (with a maximum of 64.3\%), soil moisture. Heterotrophs contributed to the majority of soil CO2 efflux, with respiration remaining unchanged when roots and/or AMF hyphae were excluded as the partitioning treatments were statistically indistinguishable. Overall, our results indicate that future warming is likely to substantially increase the largely heterotroph-driven soil C fluxes in this tropical montane grassland ecosystem.

}, doi = {10.1016/j.agrformet.2019.107619}, author = {Tiruvaimozhi, Yadugiri V and Sankaran, Mahesh} } @article {64330, title = {Specialized structural and functional roles of residues selectively conserved in subfamilies of the pleckstrin homology domain family.}, journal = {FEBS Open Bio}, year = {2019}, month = {2019 Aug 22}, abstract = {

Homologous domains embedded in multi-domain proteins of different domain architectures may exhibit subtle, but important, differences in their structure and function. Here we consider two multi-domain proteins, ARNO and GRK2, which have very different domain architectures but both contain pleckstrin homology (PH) domains. We analyzed the roles of residues selectively conserved in these sub-families of PH-domains from ARNO and GRK2 proteins. Domain architecture-specific residues in PH-domain are found to contribute to structural and functional specialization of ARNO and GRK2 in terms of (i) specific intra- and inter-protein interactions, (ii) specificity for phospholipids and (iii) participation in conformational excursions, leading to various functional forms. Our approach can also be applied to subfamilies of other protein families to identify subfamily-specific residues and their specialized roles.

}, issn = {2211-5463}, doi = {10.1002/2211-5463.12725}, author = {Naveenkumar, Nagarajan and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {59701, title = {Species composition and elevational distribution of bumble bees (Hymenoptera, Apidae, Latreille) in the East Himalaya, Arunachal Pradesh, India.}, journal = {Zookeys}, volume = {851}, year = {2019}, month = {2019}, pages = {71-89}, abstract = {

The East Himalaya is one of the world{\textquoteright}s most biodiverse ecosystems. However, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high elevation insects that fulfil an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Systematic study of Himalayan bumble bees began a few decades ago and the main focus has centred on the western region, while the eastern part of the mountain range has received little attention and only a few species have been verified. During a three-year survey, more than 700 bumble bee specimens of 21 species were collected in Arunachal Pradesh, the largest of the north-eastern states of India. The material included a range of species that were previously known from a limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat, and conservation. Clear elevation patterns of species diversity were observed, which raise important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya.

}, issn = {1313-2989}, doi = {10.3897/zookeys.851.32956}, author = {Streinzer, Martin and Chakravorty, Jharna and Neumayer, Johann and Megu, Karsing and Narah, Jaya and Schmitt, Thomas and Bharti, Himender and Spaethe, Johannes and Brockmann, Axel} } @article {66848, title = {Spoiled for Choice: Diverse Endocytic Pathways Function at the Cell Surface.}, journal = {Annu Rev Cell Dev Biol}, volume = {35}, year = {2019}, month = {2019 Oct 06}, pages = {55-84}, abstract = {

Endocytosis has long been identified as a key cellular process involved in bringing in nutrients, in clearing cellular debris in tissue, in the regulation of signaling, and in maintaining cell membrane compositional homeostasis. While clathrin-mediated endocytosis has been most extensively studied, a number of clathrin-independent endocytic pathways are continuing to be delineated. Here we provide a current survey of the different types of endocytic pathways available at the cell surface and discuss a new classification and plausible molecular mechanisms for some of the less characterized pathways. Along with an evolutionary perspective of the origins of some of these pathways, we provide an appreciation of the distinct roles that these pathways play in various aspects of cellular physiology, including the control of signaling and membrane tension.

}, issn = {1530-8995}, doi = {10.1146/annurev-cellbio-100617-062710}, author = {Thottacherry, Joseph Jose and Sathe, Mugdha and Prabhakara, Chaitra and Mayor, Satyajit} } @article {53186, title = {Stress Elicits Contrasting Effects on the Structure and Number of Astrocytes in the Amygdala versus Hippocampus.}, journal = {eNeuro}, volume = {6}, year = {2019}, month = {2019 Jan-Feb}, abstract = {

Stress causes divergent patterns of structural and physiological plasticity in the hippocampus versus amygdala. However, a majority of earlier studies focused primarily on neurons. Despite growing evidence for the importance of glia in health and disease, relatively little is known about how stress affects astrocytes. Further, previous work focused on hippocampal astrocytes. Hence, we examined the impact of chronic immobilization stress (2 h/d, 10 d), on the number and structure of astrocytes in the rat hippocampus and amygdala. We observed a reduction in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes in the basal amygdala (BA), 1 d after the end of 10 d of chronic stress. Detailed morphometric analysis of individual dye-filled astrocytes also revealed a decrease in the neuropil volume occupied by these astrocytes in the BA, alongside a reduction in the volume fraction of fine astrocytic protrusions rather than larger dendrite-like processes. By contrast, the same chronic stress had no effect on the number or morphology of astrocytes in hippocampal area CA3. We also confirmed previous reports that chronic stress triggers dendritic hypertrophy in dye-filled BA principal neurons that were located adjacent to astrocytes that had undergone atrophy. Thus, building on earlier evidence for contrasting patterns of stress-induced plasticity in neurons across brain areas, our findings offer new evidence that the same stress can also elicit divergent morphological effects in astrocytes in the hippocampus versus the amygdala.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0338-18.2019}, author = {Naskar, Saptarnab and Chattarji, Sumantra} } @article {66083, title = {Strong but opposing effects of associational resistance and susceptibility on defense phenotype in an African savanna plant}, journal = {OIKOS}, year = {2019}, month = {08/2019}, abstract = {

The susceptibility of plants to herbivores can be strongly influenced by the identity, morphology and palatability of neighboring plants. While the defensive traits of neighbors often determine the mechanism and strength of associational resistance and susceptibility, the effect of neighbors on plant defense phenotype remains poorly understood. We used field surveys and a prickle-removal experiment in a semi-arid Kenyan savanna to evaluate the efficacy of physical defenses against large mammalian herbivores in a common understory plant, Solanum campylacanthum. We then quantified the respective effects of spinescent Acacia trees and short-statured grasses on browsing damage and prickle density in S. campylacanthum. We paired measurements of prickle density beneath and outside tree canopies with long-term herbivore-exclusion experiments to evaluate whether associational resistance reduced defense investment by decreasing browsing damage. Likewise, we compared defense phenotype within and outside pre-existing and experimentally created clearings to determine whether grass neighbors increased defense investment via associational susceptibility. Removing prickles increased the frequency of browsing by ~25\%, and surveys of herbivory damage on defended leaves suggested that herbivores tended to avoid prickles. As predicted, associational resistance and susceptibility had opposing effects on plant phenotype: individuals growing beneath Acacia canopies (or, analogously, within large-herbivore exclosures) had a significantly lower proportion of their leaves browsed and produced ~ 70{\textendash}80\% fewer prickles than those outside refuges, whereas plants in grass-dominated clearings were more heavily browsed and produced nearly twice as many prickles as plants outside clearings. Our results demonstrate that associational resistance and susceptibility have strong, but opposing, effects on plant defense phenotype, and that variable herbivore damage is a major source of intraspecific variation in defense phenotype in this system.

}, doi = {10.1111/oik.06644}, author = {Coverdale, TC and McGeary, IJ and O{\textquoteright}Connell, RD and Palmer, TM and Goheen, JR and Sankaran, M and Augustine, DJ and Ford, AT and Pringle, RM} } @article {62762, title = {Structure-based mechanism for activation of the AAA+ GTPase McrB by the endonuclease McrC.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Jul 11}, pages = {3058}, abstract = {

The AAA+ GTPase McrB powers DNA cleavage by the endonuclease McrC. The GTPase itself is activated by McrC. The architecture of the GTPase and nuclease complex, and the mechanism of their activation remained unknown. Here, we report a 3.6 {\r A} structure of a GTPase-active and DNA-binding deficient construct of McrBC. Two hexameric rings of McrB are bridged by McrC dimer. McrC interacts asymmetrically with McrB protomers and inserts a stalk into the pore of the ring, reminiscent of the γ subunit complexed to αβ of F-ATPase. Activation of the GTPase involves conformational changes of residues essential for hydrolysis. Three consecutive nucleotide-binding pockets are occupied by the GTP analogue 5{\textquoteright}-guanylyl imidodiphosphate and the next three by GDP, which is suggestive of sequential GTP hydrolysis.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-11084-1}, author = {Nirwan, Neha and Itoh, Yuzuru and Singh, Pratima and Bandyopadhyay, Sutirtha and Vinothkumar, Kutti R and Amunts, Alexey and Saikrishnan, Kayarat} } @article {74434, title = {Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8.}, journal = {Cell Rep}, volume = {29}, year = {2019}, month = {2019 Nov 26}, pages = {2546-2555.e4}, abstract = {

Antimicrobial peptides (AMPs) are the body{\textquoteright}s natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon understanding the regulatory mechanisms governing their unconventional secretion from cells. Analysis of the secretion of S100A7 (Psoriasin), an abundant AMP stored in differentiated keratinocytes of the skin, has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1, and interleukin (IL)-1α. The initial activation of this core machinery is mediated by Toll-like receptor signaling, whereas the chronic response is mediated by Caspase-8 downregulation. Interestingly, there is a concomitant downregulation of Caspase-8 in inflammatory skin diseases wherein S100A7 is constitutively released. These results highlight the potential of targeting these components to control the release of AMPs from the skin in both homeostatic and disease conditions.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2019.10.090}, author = {Bhatt, Tanay and Bhosale, Aishwarya and Bajantri, Bhavya and Mathapathi, Mruthyunjaya Swamy and Rizvi, Abrar and Scita, Giorgio and Majumdar, Amitabha and Jamora, Colin} } @article {53190, title = {A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.}, journal = {Exp Cell Res}, year = {2019}, month = {2019 Feb 14}, abstract = {

Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data from The Cancer Genome Atlas (TCGA), immunohistochemistry, genomics and functional assays. Cervical cancer cells sorted based on migratory ability in vitro have low levels of SUV39H1 protein, and SUV39H1 knockdown in vitro enhanced cervical cancer cell migration. Further, TCGA SUV39H1-low tumours correlated with poor clinical outcomes and showed gene expression signatures of cell migration. SUV39H1 expression was examined within biopsies, and SUV39H1 cells within tumours also demonstrated migratory features. Next, to understand genome scale transcriptional and chromatin changes in migratory populations, cell populations sorted based on migration in vitro were examined using RNA-Seq, along with ChIP-Seq for H3K9me3, the histone mark associated with SUV39H1. Migrated populations showed SUV39H1-linked migratory gene expression signatures, along with broad depletion of H3K9me3 across gene promoters. We show for the first time that a SUV39H1-low chromatin state associates with, and promotes, migratory populations in cervical cancers. Our results posit SUV39H1-low cells as key populations for prognosis estimation and as targets for novel therapies.

}, issn = {1090-2422}, doi = {10.1016/j.yexcr.2019.02.010}, author = {Rodrigues, Calvin and Pattabiraman, Chitra and Vijaykumar, Anjali and Arora, Reety and Narayana, Suma Mysore and Kumar, Rekha V and Notani, Dimple and Varga-Weisz, Patrick and Krishna, Sudhir} } @article {67827, title = {On the systematic status of the genus Oriocalotes G{\"u}nther, 1864~(Squamata: Agamidae: Draconinae) with the description of a new species from Mizoram state, Northeast India.}, journal = {Zootaxa}, volume = {4638}, year = {2019}, month = {2019 Jul 18}, pages = {zootaxa.4638.4.1}, abstract = {

The montane agamid lizard genus Oriocalotes is currently considered monotypic, represented by the species, O. paulus. The systematic status of this taxon has remained questionable since its initial descriptions in the mid-1800s. A detailed molecular and morphological study was carried out to assess the validity of this genus, and its systematic position within the Asian agamid subfamily, Draconinae. Freshly collected and historical museum specimens from the type locality of O. paulus were examined morphologically, along with additional samples collected from localities in Mizoram state, Northeast India. Utilising newly generated molecular sequences (two mitochondrial and three nuclear genes), combined with those previously published for representative genera from the subfamilies Draconinae and Agaminae, Maximum Likelihood and Bayesian phylogenetic trees were constructed. Phylogenetic results suggest that Oriocalotes is part of the widespread South and Southeast Asian radiation of Calotes. Comparative morphological studies (including external morphology, hemipenis and osteology) between Oriocalotes and related genera further support this systematic placement. Oriocalotes is herein regarded as a junior subjective synonym of Calotes. Calotes paulus comb. nov. is also assigned a lectotype and given a detailed redescription based on the lectotype, paralectotypes and additional topotypic material. Furthermore, the specimens collected from Mizoram populations are found to be morphologically and genetically distinct from Calotes paulus comb. nov., and are described herein as a new species, Calotes zolaiking sp. nov.

}, keywords = {Animals, Bayes Theorem, India, Lizards, Osteology, Phylogeny}, issn = {1175-5334}, doi = {10.11646/zootaxa.4638.4.1}, author = {Giri, Varad B and Chaitanya, R and Mahony, Stephen and Lalrounga, Samuel and Lalrinchhana, C and Das, Abhijit and Sarkar, Vivek and Karanth, Praveen and Deepak, V} } @article {67836, title = {Targeting redox heterogeneity to counteract drug tolerance in replicating .}, journal = {Sci Transl Med}, volume = {11}, year = {2019}, month = {2019 Nov 13}, abstract = {

The capacity of () to tolerate multiple antibiotics represents a major problem in tuberculosis (TB) management. Heterogeneity in populations is one of the factors that drives antibiotic tolerance during infection. However, the mechanisms underpinning this variation in bacterial population remain poorly understood. Here, we show that phagosomal acidification alters the redox physiology of to generate a population of replicating bacteria that display drug tolerance during infection. RNA sequencing of this redox-altered population revealed the involvement of iron-sulfur (Fe-S) cluster biogenesis, hydrogen sulfide (HS) gas, and drug efflux pumps in antibiotic tolerance. The fraction of the pH- and redox-dependent tolerant population increased when infected macrophages with actively replicating HIV-1, suggesting that redox heterogeneity could contribute to high rates of TB therapy failure during HIV-TB coinfection. Pharmacological inhibition of phagosomal acidification by the antimalarial drug chloroquine (CQ) eradicated drug-tolerant , ameliorated lung pathology, and reduced postchemotherapeutic relapse in in vivo models. The pharmacological profile of CQ ( and AUC) exhibited no major drug-drug interaction when coadministered with first line anti-TB drugs in mice. Our data establish a link between phagosomal pH, redox metabolism, and drug tolerance in replicating and suggest repositioning of CQ to shorten TB therapy and achieve a relapse-free cure.

}, issn = {1946-6242}, doi = {10.1126/scitranslmed.aaw6635}, author = {Mishra, Richa and Kohli, Sakshi and Malhotra, Nitish and Bandyopadhyay, Parijat and Mehta, Mansi and Munshi, MohamedHusen and Adiga, Vasista and Ahuja, Vijay Kamal and Shandil, Radha K and Rajmani, Raju S and Seshasayee, Aswin Sai Narain and Singh, Amit} } @article {70225, title = {Temperature patterns and mechanisms influencing coral bleaching during the 2016 El Nino}, journal = {Nature Climate Change}, volume = {9}, year = {2019}, month = {09/2019}, pages = {845{\textendash}851}, type = {Letter}, abstract = {

Under extreme heat stress, corals expel their symbiotic algae and colour (that is, {\textquoteleft}bleaching{\textquoteright}), which often leads to widespread mortality. Predicting the large-scale environmental conditions that reinforce or mitigate coral bleaching remains unresolved and limits strategic conservation actions1,2. Here we assessed coral bleaching at 226 sites and 26 environmental variables that represent different mechanisms of stress responses from East Africa to Fiji through a coordinated effort to evaluate the coral response to the 2014{\textendash}2016 El Ni{\~n}o/Southern Oscillation thermal anomaly. We applied common time-series methods to study the temporal patterning of acute thermal stress and evaluated the effectiveness of conventional and new sea surface temperature metrics and mechanisms in predicting bleaching severity. The best models indicated the importance of peak hot temperatures, the duration of cool temperatures and temperature bimodality, which explained ~50\% of the variance, compared to the common degree-heating week temperature index that explained only 9\%. Our findings suggest that the threshold concept as a mechanism to explain bleaching alone was not as powerful as the multidimensional interactions of stresses, which include the duration and temporal patterning of hot and cold temperature extremes relative to average local conditions.

}, doi = {10.1038/s41558-019-0576-8}, author = {McClanahan, Tim R and Darling, Emily S and Maina, Joseph M and Muthiga, Nyawira A and D{\textquoteright}agata, Stephanie and Jupiter, Stacy D and Arthur, Rohan and Wilson, Shaun K and Mangubhai, Sangeeta and Nand, Yashika and Ussi, Ali M and Humphries, Austin T and Patankar, Vardhan J and Guillaume, Mireille M and Keith, Sally A and Shedrawi, George and Julius, Pagu and Grimsditch, Gabriel and Ndagala, January and Leblond, Julien} } @article {62771, title = {A thorny issue: Woody plant defence and growth in an East African savanna}, journal = {JOURNAL OF ECOLOGY}, volume = {107}, year = {2019}, month = {07/2019}, pages = {1839-1851}, doi = {10.1111/1365-2745.13140}, author = {Wigley, BJ and Coetsee, C and Augustine, DJ and Ratnam, J and Hattas, D and Sankaran, M.} } @article {45306, title = {Timing is everything: differential effects of chronic stress on fear extinction.}, journal = {Psychopharmacology (Berl)}, volume = {236}, year = {2019}, month = {2018 Oct 10}, pages = {73-86}, abstract = {

RATIONALE: Stress disorders cause abnormal regulation of fear-related behaviors. In most rodent models of these effects, stress was administered before fear conditioning, thereby assessing its impact on both the formation and extinction of fear memories, not the latter alone. Here, we dissociated the two processes by also administering stress after fear conditioning, and then compared how pre-conditioning versus post-conditioning exposure to chronic stress affects subsequent acquisition and recall of fear extinction.

METHODS: Male Wistar rats were subjected to chronic immobilization stress (2\ h/day, 10\ days); the morphological effects of which were analyzed using modified Golgi-Cox staining across brain areas mediating the formation and extinction of fear memories. Separate groups of rats underwent fear conditioning followed by acquisition and recall of extinction, wherein stress was administered either before or after fear conditioning.

RESULTS: When fear memories were formed after chronic stress, both acquisition and retrieval of extinction was impaired. Strikingly, these deficits were absent when fear memories were formed before the same stress. Chronic stress also reduced dendritic spine density in the infralimbic prefrontal cortex, but enhanced it in the basolateral amygdala.

CONCLUSION: Chronic stress, administered either before or after fear learning, had distinct effects on the acquisition and recall of fear extinction memories. Stress also strengthened the structural basis of synaptic connectivity in the amygdala, but weakened it in the prefrontal cortex. Thus, despite eliciting a specific pattern of brain region-specific morphological changes, the timing of the same stress gave rise to strikingly different behavioral effects on the extinction of fear.

}, issn = {1432-2072}, doi = {10.1007/s00213-018-5053-y}, author = {Chakraborty, Prabahan and Chattarji, Sumantra} } @article {60326, title = {Topology prediction of insect olfactory receptors.}, journal = {Curr Opin Struct Biol}, volume = {55}, year = {2019}, month = {2019 Jun 21}, pages = {194-203}, abstract = {

Olfactory receptors are important transmembrane proteins that enable organisms to perceive odours and react to them. Structural understanding of insect olfactory receptors is scarce. In this review, we discuss different transmembrane helix prediction methods, consensus methods, topology prediction methods which can enable topology prediction of these proteins. We discuss the current success rates by applying the algorithms on few G-protein coupled receptors of known structure and olfactory receptor sequences and outstanding challenges. Finally, we discuss the impact of topology prediction on biology and modeling of ORs.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2019.05.014}, author = {Tiwari, Vikas and Karpe, Snehal D and Sowdhamini, Ramanathan} } @article {59708, title = {Tracking Bacterial Chromosome Dynamics with Microfluidics-Based Live Cell Imaging.}, journal = {Methods Mol Biol}, volume = {2004}, year = {2019}, month = {2019}, pages = {223-238}, abstract = {

In bacteria, chromosomes are highly organized within the limited volume of the cell to form a nucleoid. Recent application of microscopy and chromosome conformation capture techniques have together provided a comprehensive understanding of the nature of this organization and the role of factors such as the structural maintenance of chromosomes (SMC) proteins in the establishment and maintenance of the same. In this chapter, we outline a microfluidics-based approach for live cell imaging of Escherichia coli chromosome dynamics in wild-type cells. This assay can be used to track the activity of the SMC complex, MukBEF, on DNA and assess the impact of perturbations such as DNA damage on chromosome organization and segregation.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-9520-2_17}, author = {Raghunathan, Suchitha and Badrinarayanan, Anjana} } @article {69323, title = {Tuneable reflexes control antennal positioning in flying hawkmoths.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Dec 06}, pages = {5593}, abstract = {

Complex behaviours may be viewed as sequences of modular actions, each elicited by specific sensory cues in their characteristic timescales. From this perspective, we can construct models in which unitary behavioural modules are hierarchically placed in context of related actions. Here, we analyse antennal positioning reflex in hawkmoths as a tuneable behavioural unit. Mechanosensory feedback from two antennal structures, B{\"o}hm{\textquoteright}s bristles (BB) and Johnston{\textquoteright}s organs (JO), determines antennal position. At flight onset, antennae attain a specific position, which is maintained by feedback from BB. Simultaneously, JO senses deflections in flagellum-pedicel joint due to frontal airflow, to modulate its steady-state position. Restricting JO abolishes positional modulation but maintains stability against perturbations. Linear feedback models are sufficient to predict antennal dynamics at various set-points. We modelled antennal positioning as a hierarchical neural-circuit in which fast BB feedback maintains instantaneous set-point, but slow JO feedback modulates it, thereby elucidating mechanisms underlying its robustness and flexibility.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-13595-3}, author = {Natesan, Dinesh and Saxena, Nitesh and Ekeberg, {\"O}rjan and Sane, Sanjay P} } @article {67824, title = {Two more new species of Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from the northern Western Ghats, Maharashtra, India.}, journal = {Zootaxa}, volume = {4656}, year = {2019}, month = {2019 Aug 13}, pages = {zootaxa.4656.1.2}, abstract = {

We describe two new species of the gekkonid genus Cnemaspis from the northern Western Ghats in Maharashtra, India. Cnemaspis amba sp. nov. and C. koynaensis sp. nov. are members of the C. girii clade and differ genetically from each other and other members of the clade by -7.9-19.6 \% uncorrected ND2 sequence divergence. The two new species are also morphologically distinguishable from all regional congeners on the basis of condition of spine-like scales on flanks, heterogeneity of dorsal pholidosis, number of dorsal tubercle rows, number of tubercles in paravertebral rows, femoral pores, number of poreless scales between femoral pores in the precloacal-femoral scale row, and keeling and size of sub-caudal scales. Cnemaspis amba sp. nov. differs from C. koynaensis sp. nov. in lacking\  spine-like scales on flanks and in the number of longitudinal ventral scales and\  ventral scales across mid-body. Both species are known only from their mid-elevation (~800 m asl.) type localities. Discovery of two new species increases the total species of Northern Western Ghats (NWG) Cnemaspis to ten. Specific status of numerous genetically divergent lineages needs to be evaluated and it is likely that many more species remain to be discovered from the poorly explored NWG, which are typically considered low in species diversity relative to more southern regions. We also provide a table describing major diagnostic characters across all NWG Cnemaspis species and corrected type locality data for three recently named species-Cnemaspis ajijae, C. limayei and C. mahabali.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4656.1.2}, author = {Khandekar, Akshay and Thackeray, Tejas and Agarwal, Ishan} } @article {67823, title = {Two new Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from the Shevaroy massif, Tamil Nadu, India, with a preliminary ND2 phylogeny of Indian Cnemaspis.}, journal = {Zootaxa}, volume = {4609}, year = {2019}, month = {2019 May 22}, pages = {zootaxa.4609.1.3}, abstract = {

We present a preliminary ND2 phylogeny of South Asian Cnemaspis, recovering a number of deeply divergent clades within Indian Cnemaspis, endemic to the southern and northern Western Ghats besides the Mysore Plateau and hills of Tamil Nadu. There are a number of unnamed lineages that are \>5\% divergent on ND2 across the phylogeny, including three from the gracilis clade on an elevation gradient (800-1400 m asl.) around Yercaud in the Shevaroy massif, Salem district, Tamil Nadu. We describe two of these as new species- Cnemaspis shevaroyensis sp. nov. and Cnemaspis thackerayi sp. nov. are both allied to Cnemaspis gracilis and can be diagnosed from all other Indian Cnemaspis by the absence of spine-like scales on flank, heterogeneous dorsal pholidosis, presence of femoral and precloacal pores, tail with enlarged, strongly keeled, conical tubercles forming whorls, a median row of enlarged and smooth sub-caudals. They differ from C. gracilis and each other in body size, the number of tubercles around midbody, the number of tubercles in paravertebral rows, the number of femoral and precloacal pores, the number of poreless scales in-between precloacal pores and between femoral and precloacal pores, and subtle colour pattern differences; besides uncorrected mitochondrial sequence divergence (7.9-16.6 \%). We also provide a description of Cnemaspis yercaudensis from its type locality and an additional locality. The discovery of two endemic species and a third unnamed divergent lineage from an isolated massif in peninsular India outside the Western Ghats indicate that many other such understudied hill ranges may harbour high endemic biodiversity.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4609.1.3}, author = {Khandekar, Akshay and Gaitonde, Nikhil and Agarwal, Ishan} } @article {43842, title = {Vaccination and immunization strategies to design Aedes aegypti salivary protein based subunit vaccine tackling Flavivirus infection.}, journal = {Int J Biol Macromol}, volume = {122}, year = {2019}, month = {2018 Sep 13}, pages = {1203-1211}, abstract = {

Flavivirus causes arthropod-borne severe diseases that sometimes lead to the death. The Flavivirus species including Dengue virus, Zika virus and yellow fever virus are transmitted by the bite of Aedes mosquitoes. All these viral species target the people living in their respective endemic zone causing a high mortality rate. Recent studies show that immune factors present in the Ae. aegypti saliva is the hidden culprit promoting blood meal collection, suppressing host immune molecules and promoting disease establishment. This study was designed to develop a subunit vaccine using Aedes mosquito salivary proteins targeting the aforementioned Flaviviruses. Subunit vaccine was designed very precisely by combining the immunogenic B-cell epitope with CTL and HTL epitopes and also suitable adjuvant and linkers. Immunogenicity, allergenicity and physiochemical characterization were also performed for scientific validation. Molecular docking and molecular dynamics simulations studies were carried out to confirm the stable affinity between the vaccine protein (3D) and TLR3 receptor. At last, in silico cloning was executed to get the subunit vaccine restriction clone into pET28a vectro to express it in microbial expression system. Additionally, this study warrants the experimental evaluation for the validation purposes.

}, issn = {1879-0003}, doi = {10.1016/j.ijbiomac.2018.09.071}, author = {Pandey, Rajan Kumar and Dahiya, Surbhi and Mahita, Jarjapu and Sowdhamini, Ramanathan and Prajapati, Vijay Kumar} } @article {43852, title = {Antagonistic pleiotropy for carbon use is rare in new mutations.}, journal = {Evolution}, year = {2018}, month = {2018 Aug 10}, abstract = {

Pleiotropic effects of mutations underlie diverse biological phenomena such as ageing and specialization. In particular, antagonistic pleiotropy ("AP": when a mutation has opposite fitness effects in different environments) generates tradeoffs, which may constrain adaptation. Models of adaptation typically assume that AP is common - especially among large-effect mutations - and that pleiotropic effect sizes are positively correlated. Empirical tests of these assumptions have focused on de novo beneficial mutations arising under strong selection. However, most mutations are actually deleterious or neutral, and may contribute to standing genetic variation that can subsequently drive adaptation. We quantified the incidence, nature, and effect size of pleiotropy for carbon utilization across 80 single mutations in Escherichia coli that arose under mutation accumulation (i.e., weak selection). Although \~{}46\% of the mutations were pleiotropic, only 11\% showed AP; among beneficial mutations, only \~{}4\% showed AP. In some environments, AP was more common in large-effect mutations; and AP effect sizes across environments were often negatively correlated. Thus, AP for carbon use is generally rare (especially among beneficial mutations); is not consistently enriched in large-effect mutations; and often involves weakly deleterious antagonistic effects. Our unbiased quantification of mutational effects therefore suggests that antagonistic pleiotropy may be unlikely to cause maladaptive tradeoffs.

}, issn = {1558-5646}, doi = {10.1111/evo.13569}, author = {Sane, Mrudula and Miranda, Joshua John and Agashe, Deepa} } @article {45928, title = {Ants on Clerodendrum infortunatum: Disentangling Effects of Larceny and Herbivory.}, journal = {Environ Entomol}, volume = {47}, year = {2018}, month = {2018 Oct 03}, pages = {1143-1151}, abstract = {

Nectar larcenists extract nectar from flowers without pollinating them. A reasonable expectation is that any form of nectar larceny should have a detrimental effect on the plant{\textquoteright}s reproductive success. However, studies reveal an entire range of effects, from highly negative to highly positive. This variation in effect may be partly explained by additional, unmeasured, effects of nectar larcenists on plants. In a study system where two ant species Tapinoma melanocephalum (Fabr.) (Hymenoptera: Formicidae) and Trichomyrmex destructor (Jerd.) (Hymenoptera: Formicidae) act as nectar larcenists, we examined the effect of larceny on the female reproductive success of Clerodendrum infortunatum Gaertn. (Lamiales: Lamiaceae) in rain forest fragments of the Western Ghats, India. This was done through a combination of field observations and a series of field experiments looking at the effects of excluding ants from inflorescences. We found that T. destructor reduces fruit set considerably. Rather than this being a consequence of nectar larceny, however, our experiments show that the negative effect arises instead from the herbivorous behavior of the ant. At a population level, both ant species prefer edges over interiors of forest patches, spatially concentrating the interaction zone to forest edges. Simultaneously considering multiple ecological interactions and disentangling their relative contributions might explain the large variation across species in the observed effect of larceny. The overall population effect of nectar larceny and herbivory is likely to depend on the spatial structuring of plants and ants.

}, issn = {1938-2936}, doi = {10.1093/ee/nvy090}, author = {Mukhopadhyay, Amritendu and Quader, Suhel} } @article {45444, title = {Breeding Biology of Great Hornbill Buceros bicornis in Tropical Rainforest and Human-Modified Plantation Landscape in Western Ghats, India}, journal = {Ornithological Science}, volume = {17}, year = {2018}, month = {07/2018}, pages = {205-216}, abstract = {

Loss of mature tropical forests to agricultural expansion often creates landscapes with forest fragments embedded within a matrix of human-modified habitats and land uses. Such habitat fragmentation may be detrimental to species with specialized habitat and foraging requirements and their ability to persist in such landscapes may depend on their adaptability to habitat modification. Great Hornbills Buceros bicornis, among the largest birds in Asian tropical rainforests, depend on large trees for nesting and a diverse array of patchily distributed fruiting trees. In the human-modified landscape of the Anamalai Hills, India, we compared the breeding biology and nesting behaviour of Great Hornbills in contiguous rainforest (N=3 nests) and in modified habitat consisting of coffee plantations and rainforest fragments (N=5 nests). The nesting cycle of seven of the eight nests monitored varied between 114 and 130 days. Nest provisioning behaviour was similar in contiguous forest and modified habitat in terms of visitation and food delivery rates, but visitation tended to be higher and food delivery rate lower during the nestling phase than during incubation. As expected, tree density and native food plant diversity were lower in modified habitat than in continuous forest. The diversity of food provisioned was lower in modified habitat with a 57.5\% dietary overlap with contiguous forest. Hornbills in the modified habitat of coffee plantations used non-native tree species for nesting and foraging, indicating their adaptability to modified landscapes.

}, doi = {10.2326/osj.17.205}, author = {Pawar, Pooja and Naniwadekar, R and Shankar Raman, T R and Mudappa, Divya} } @article {36262, title = {Bush encroachment influences nocturnal rodent community and behaviour in a semi-arid grassland in Gujarat, India }, journal = {Journal of Arid Environments}, volume = {153}, year = {2018}, month = {06/2018}, pages = {32-38}, abstract = {

Bush encroachment is one of the major threats to grasslands globally. The increased cover due to bush encroachment can strongly influence the behaviour of animals adapted to a more open habitat. In this study, we explored the effects of bush encroachment on the foraging behaviour of nocturnal rodents the semi-arid Banni grasslands of western India, once one of India{\textquoteright}s largest tropical grassland habitats. We quantified foraging behaviour using the giving-up density (GUD) framework, across two sites that differed in the extent of bush encroachment. Rodents in the site with high bush encroachment (the dense site) exhibited higher foraging costs (higher GUD) in early summer compared to the site with low bush encroachment (the sparse site). Rodents in the dense site also had lower activity. The dense site supported higher richness and relative abundance of generalist rodents than the sparse site. Our results suggest that bush encroachment may be associated with higher foraging costs for nocturnal rodents and result in a change in species composition of rodents. Given the ecosystem engineering services performed by native grassland species, these results can have negative implications for grassland restoration.

}, doi = {10.1016/j.jaridenv.2017.12.009 }, author = {Jayadevan, A and Mukherjee, S and Vanak, AT} } @article {36658, title = {: A Candidate Transcription Factor Involved in Molecular Processes Underlying Time-Memory.}, journal = {Front Psychol}, volume = {9}, year = {2018}, month = {2018}, pages = {865}, abstract = {

In honey bees, continuous foraging is accompanied by a sustained up-regulation of the immediate early gene (early growth response protein-1) and candidate downstream genes involved in learning and memory. Here, we present a series of feeder training experiments indicating that expression is highly correlated with the time and duration of training even in the absence of the food reward. Foragers that were trained to visit a feeder over the whole day and then collected on a day without food presentation showed up-regulation over the whole day with a peak expression around 14:00. When exposed to a time-restricted feeder presentation, either 2 h in the morning or 2 h in the evening, expression in the brain was up-regulated only during the hours of training. Foragers that visited a feeder in the morning as well as in the evening showed two peaks of expression. Finally, when we prevented time-trained foragers from leaving the colony using artificial rain, expression in the brains was still slightly but significantly up-regulated around the time of feeder training. hybridization studies showed that active foraging and time-training induced up-regulation occurred in the same brain areas, preferentially the small Kenyon cells of the mushroom bodies and the antennal and optic lobes. Based on these findings we propose that foraging induced expression can get regulated by the circadian clock after time-training over several days and is a candidate transcription factor involved in molecular processes underlying time-memory.

}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.00865}, author = {Shah, Aridni and Jain, Rikesh and Brockmann, Axel} } @article {30721, title = {Cargo crowding at actin-rich regions along axons causes local traffic jams.}, journal = {Traffic}, volume = {19}, year = {2018}, month = {2018 Mar}, pages = {166-181}, abstract = {

Steady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary up to several minutes. We examine the transport of precursors of synaptic vesicles (pre-SVs), endosomes and mitochondria in Caenorhabditis elegans touch receptor neurons, showing that stationary cargo are predominantly present at actin-rich regions along the neuronal process. Stationary vesicles at actin-rich regions increase the propensity of moving vesicles to stall at the same location, resulting in traffic jams arising from physical crowding. Such local traffic jams at actin-rich regions are likely to be a general feature of axonal transport since they also occur in Drosophila neurons. Repeated touch stimulation of C. elegans reduces the density of stationary pre-SVs, indicating that these traffic jams can act as both sources and sinks of vesicles. This suggests that vesicles trapped in actin-rich regions are functional reservoirs that may contribute to maintaining robust cargo flow in the neuron. A video abstract of this article can be found at: Video S1; Video S2.

}, issn = {1600-0854}, doi = {10.1111/tra.12544}, author = {Sood, Parul and Murthy, Kausalya and Kumar, Vinod and Nonet, Michael L and Menon, Gautam I and Koushika, Sandhya P} } @article {45431, title = {Cascade of transitions in molecular information theory}, journal = {Journal of Statistical Mechanics: Theory and Experiment}, volume = {Art No. 093402}, year = {2018}, month = {10/2018}, abstract = {

Biological organisms are open, adaptive systems that can respond to changes in environment in specific ways. Adaptation and response can be posed as an optimization problem, with a tradeoff between the benefit obtained from a response and the cost of producing environment-specific responses. Using recent results in stochastic thermodynamics, we formulate the cost as the mutual information between the environment and the stochastic response. The problem of designing an optimally performing network now reduces to a problem in rate distortion theory{\textemdash}a branch of information theory that deals with lossy data compression. We find that as the cost of unit information goes down, the system undergoes a sequence of transitions, corresponding to the recruitment of an increasing number of responses, thus improving response specificity as well as the net payoff. We derive formal equations for the transition points and exactly solve them for special cases. The first transition point, also called the coding transition, demarcates the boundary between a passive response and an active decision-making by the system. We study this transition point in detail, and derive three classes of asymptotic behavior, corresponding to the three limiting distributions of the statistics of extreme values. Our work points to the necessity of a union between information theory and the theory of adaptive biomolecular networks, in particular metabolic networks.

}, doi = {10.1088/1742-5468/aaddaa}, author = {Das, S G and Rao, Madan and Iyengar, Garud} } @article {45930, title = {Change in dominance determines herbivore effects on plant biodiversity.}, journal = {Nat Ecol Evol}, year = {2018}, month = {2018 Oct 29}, abstract = {

Herbivores alter plant biodiversity (species richness) in many of the world{\textquoteright}s ecosystems, but the magnitude and the direction of herbivore effects on biodiversity vary widely within and among ecosystems. One current theory predicts that herbivores enhance plant biodiversity at high productivity but have the opposite effect at low productivity. Yet, empirical support for the importance of site productivity as a mediator of these herbivore impacts is equivocal. Here, we synthesize data from 252 large-herbivore exclusion studies, spanning a 20-fold range in site productivity, to test an alternative hypothesis-that herbivore-induced changes in the competitive environment determine the response of plant biodiversity to herbivory irrespective of productivity. Under this hypothesis, when herbivores reduce the abundance (biomass, cover) of dominant species (for example, because the dominant plant is palatable), additional resources become available to support new species, thereby increasing biodiversity. By contrast, if herbivores promote high dominance by increasing the abundance of herbivory-resistant, unpalatable species, then resource availability for other species decreases reducing biodiversity. We show that herbivore-induced change in dominance, independent of site productivity or precipitation (a proxy for productivity), is the best predictor of herbivore effects on biodiversity in grassland and savannah sites. Given that most herbaceous ecosystems are dominated by one or a few species, altering the competitive environment via herbivores or by other means may be an effective strategy for conserving biodiversity in grasslands and savannahs globally.

}, issn = {2397-334X}, doi = {10.1038/s41559-018-0696-y}, author = {Koerner, Sally E and Smith, Melinda D and Burkepile, Deron E and Hanan, Niall P and Avolio, Meghan L and Collins, Scott L and Knapp, Alan K and Lemoine, Nathan P and Forrestel, Elisabeth J and Eby, Stephanie and Thompson, Dave I and Aguado-Santacruz, Gerardo A and Anderson, John P and Anderson, T Michael and Angassa, Ayana and Bagchi, Sumanta and Bakker, Elisabeth S and Bastin, Gary and Baur, Lauren E and Beard, Karen H and Beever, Erik A and Bohlen, Patrick J and Boughton, Elizabeth H and Canestro, Don and Cesa, Ariela and Chaneton, Enrique and Cheng, Jimin and D{\textquoteright}Antonio, Carla M and Deleglise, Claire and Demb{\'e}l{\'e}, Fadiala and Dorrough, Josh and Eldridge, David J and Fernandez-Going, Barbara and Fern{\'a}ndez-Lugo, Silvia and Fraser, Lauchlan H and Freedman, Bill and Garc{\'\i}a-Salgado, Gonzalo and Goheen, Jacob R and Guo, Liang and Husheer, Sean and Karemb{\'e}, Moussa and Knops, Johannes M H and Kraaij, Tineke and Kulmatiski, Andrew and Kyt{\"o}viita, Minna-Maarit and Lezama, Felipe and Loucougaray, Gregory and Loydi, Alejandro and Milchunas, Dan G and Milton, Suzanne J and Morgan, John W and Moxham, Claire and Nehring, Kyle C and Olff, Han and Palmer, Todd M and Rebollo, Salvador and Riginos, Corinna and Risch, Anita C and Rueda, Marta and Sankaran, Mahesh and Sasaki, Takehiro and Schoenecker, Kathryn A and Schultz, Nick L and Sch{\"u}tz, Martin and Schwabe, Angelika and Siebert, Frances and Smit, Christian and Stahlheber, Karen A and Storm, Christian and Strong, Dustin J and Su, Jishuai and Tiruvaimozhi, Yadugiri V and Tyler, Claudia and Val, James and Vandegehuchte, Martijn L and Veblen, Kari E and Vermeire, Lance T and Ward, David and Wu, Jianshuang and Young, Truman P and Yu, Qiang and Zelikova, Tamara Jane} } @article {45447, title = {Comparative Population Structure in Species of Bats Differing in Ecology and Morphology in the Andaman Islands, India}, journal = {Acta Chiropterologica}, volume = {20}, year = {2018}, month = {06/2018}, pages = {85-98}, abstract = {

Gene flow results from movement between populations, homogenising gene pools and impacting genetic variation and evolution. Growing evidence suggests that movement of individuals among populations may be more strongly determined by ecological traits. We compared genetic and morphometric differentiation in four species of bats {\textemdash} Eonycteris spelaea, Cynopterus sphinx, Rhinolophus affinis and Hipposideros pomona {\textemdash} which differ in their flight capability and roosting requirement to understand their effects in shaping genetic structure. Hypervariable region I of the mitochondrial control region was amplified from 40 E. spelaea, 28 C. sphinx, 44 R. affinis and 57 H. pomona sampled from locations spread across the Andaman archipelago. Populations of E. spelaea were nearly panmictic; R. affinis were differentiated into two clusters, and H. pomona were differentiated into three clusters. Consistent genetic and morphometric clusters were obtained for C. sphinx and the genetic break for C. sphinx occurs between Middle and South Andaman Islands, coincided with the Jarawa Tribal Reserve. In conclusion, poorly-dispersing, caveroosting species show high population structure, but when flight capability is very well-developed, the effect of disjunct roost availability is offset. The genetic structure of C. sphinx where we expected panmixia, is possibly confounded by the colonization history of its two genetic lineages and its habitat use which may prevent significant gene flow between the two lineages.

}, doi = {10.3161/15081109ACC2018.20.1.006}, author = {Chakravarty, R and Chattopadhyay, Balaji and Ramakrishnan, Uma} } @article {45433, title = {Cone Snail Glutaminyl Cyclase Sequences from Transcriptomic Analysis and Mass Spectrometric Characterization of Two Pyroglutamyl Conotoxins.}, journal = {J Proteome Res}, volume = {17}, year = {2018}, month = {2018 Aug 03}, pages = {2695-2703}, abstract = {

The post-translational modification of N-terminal glutamine (Q) to a pyroglutamyl (Z) residue is observed in the conotoxins produced by marine cone snails. This conversion requires the action of the enzyme glutaminyl cyclase (QC). Four complete QC sequences from the species C. araneosus, C. frigidus, C. litteratus, and C. monile and two partial sequences from C. amadis and C. miles have been obtained by analysis of transcriptomic data. Comparisons with mammalian enzyme sequences establish a high level of identity and complete conservation of functional active site residues, including a cluster of hydrogen-bonded acidic side chains. Mass spectrometric analysis of crude venom samples coupled to conotoxin precursor protein sequences obtained from transcriptomic data establishes the presence of pyroglutamyl conotoxins in the venom of C. frigidus and C. amadis. The C. frigidus peptide belongs to the M superfamily, with cysteine framework III, whereas the C. amadis peptide belongs to the divergent superfamily with cysteine framework VI/VII. Additionally, gamma carboxylation of glutamic acid and hydroxylation of proline are observed in the C. frigidus peptide. Mass spectral data are available via ProteomeXchange with identifier PXD009006.

}, issn = {1535-3907}, doi = {10.1021/acs.jproteome.8b00132}, author = {Vijayasarathy, Marimuthu and Basheer, Soorej M and Balaram, Padmanabhan} } @article {34250, title = {Conservation lessons from large-mammal manipulations in East African savannas: the KLEE, UHURU, and GLADE experiments.}, journal = {Ann N Y Acad Sci}, year = {2018}, month = {2018 May 11}, abstract = {

African savannas support an iconic fauna, but they are undergoing large-scale population declines and extinctions of large (\>5\ kg) mammals. Long-term, controlled, replicated experiments that explore the consequences of this defaunation (and its replacement with livestock) are rare. The Mpala Research Centre in Laikipia County, Kenya, hosts three such experiments, spanning two adjacent ecosystems and environmental gradients within them: the Kenya Long-Term Exclosure Experiment (KLEE; since 1995), the Glade Legacies and Defaunation Experiment (GLADE; since 1999), and the Ungulate Herbivory Under Rainfall Uncertainty experiment (UHURU; since 2008). Common themes unifying these experiments are (1) evidence of profound effects of large mammalian herbivores on herbaceous and woody plant communities; (2) competition and compensation across herbivore guilds, including rodents; and (3) trophic cascades and other indirect effects. We synthesize findings from the past two decades to highlight generalities and idiosyncrasies among these experiments, and highlight six lessons that we believe are pertinent for conservation. The removal of large mammalian herbivores has dramatic effects on the ecology of these ecosystems; their ability to rebound from these changes (after possible refaunation) remains unexplored.

}, issn = {1749-6632}, doi = {10.1111/nyas.13848}, author = {Goheen, Jacob R and Augustine, David J and Veblen, Kari E and Kimuyu, Duncan M and Palmer, Todd M and Porensky, Lauren M and Pringle, Robert M and Ratnam, Jayashree and Riginos, Corinna and Sankaran, Mahesh and Ford, Adam T and Hassan, Abdikadir A and Jakopak, Rhiannon and Kartzinel, Tyler R and Kurukura, Samson and Louthan, Allison M and Odadi, Wilfred O and Otieno, Tobias O and Wambua, Alois M and Young, Hillary S and Young, Truman P} } @article {29733, title = {Context-dependent interactive effects of non-lethal predation on larvae impact adult longevity and body composition.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0192104}, abstract = {

Predation impacts development, behavior and morphology of prey species thereby shaping their abundances, distribution and community structure. Non-lethal threat of predation, specifically, can have a strong influence on prey lifehistory characteristics. While investigations often focus on the impact of predation threat on prey in isolation, tests of its interactive effects with food availability and resource competition on prey survival and fitness can improve understanding of costs, benefits and trade-offs of anti-predator strategies. This study, involving Aedes aegypti mosquitoes as a model organism, investigates both simple and interactive effects of predation threat during the larval stage on survival, size at and time to maturity, stored teneral reserves of glycogen, protein and lipid in adults, and adult longevity. Our results show that development times of mosquito larvae were increased (by 14.84\% in males and by 97.63\% in females), and size of eclosing adults decreased (by 62.30\% in males and by 58.33\% in females) when exposed to lowered nutrition and elevated intraspecific competition, but that predation had no detectable effect on these simple traits. Teneral reserves of glycogen, protein and lipid and adult longevity were positively correlated with adult body size. Non-lethal predation threat had significant interactive effects with nutrition and larval competition on teneral reserves in males and adult longevity in males and females. The sexes responded differently to conditions encountered as larvae, with the larval environment affecting development and adult characteristics more acutely for females than for males. The outcome of this study shows how threat of predation on juveniles can have long-lasting effects on adults that are likely to impact mosquito population dynamics and that may impact disease transmission.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0192104}, author = {Chandrasegaran, Karthikeyan and Kandregula, Samyuktha Rao and Quader, Suhel and Juliano, Steven A} } @article {36276, title = {The critically endangered forest owlet Heteroglaux blewitti is nested within the currently recognized Athene clade: A century-old debate addressed.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0192359}, abstract = {

Range-restricted species generally have specific niche requirements and may often have unique evolutionary histories. Unfortunately, many of these species severely lack basic research, resulting in poor conservation strategies. The phylogenetic relationship of the Critically Endangered Forest Owlet Heteroglaux blewitti has been the subject of a century-old debate. The current classifications based on non-phylogenetic comparisons of morphology place the small owls of Asia into three genera, namely, Athene, Glaucidium, and Heteroglaux. Based on morphological and anatomical data, H. blewitti has been alternatively hypothesized to belong within Athene, Glaucidium, or its own monotypic genus Heteroglaux. To test these competing hypotheses, we sequenced six loci (~4300 bp data) and performed phylogenetic analyses of owlets. Mitochondrial and nuclear trees were not congruent in their placement of H. blewitti. However, both mitochondrial and nuclear combined datasets showed strong statistical support with high maximum likelihood bootstrap (\>/ = 90) and Bayesian posterior probability values (\>/ = 0.98) for H. blewitti being nested in the currently recognized Athene group, but not sister to Indian A. brama. The divergence of H. blewitti from its sister taxa was between 4.3 and 5.7 Ma coinciding with a period of drastic climatic changes in the Indian subcontinent. This study presented the first genetic analysis of H. blewitti, a Critically Endangered species, and addressed the long debate on the relationships of the Athene-Heteroglaux-Glaucidium complex. We recommend further studies with more data and complete taxon sampling to understand the biogeography of Indian Athene species.

}, keywords = {Animals, Bayes Theorem, Conservation of Natural Resources, Endangered Species, Fossils, Phylogeny, Strigiformes}, issn = {1932-6203}, doi = {10.1371/journal.pone.0192359}, author = {Koparde, Pankaj and Mehta, Prachi and Reddy, Sushma and Ramakrishnan, Uma and Mukherjee, Shomita and Robin, V V} } @article {36275, title = {The curious case of Hemidactylus gujaratensis (Squamata: Gekkonidae).}, journal = {Zootaxa}, volume = {4388}, year = {2018}, month = {2018 Feb 28}, pages = {137-142}, abstract = {

Hemidactylus Oken, 1817 is one of the most speciose genera of the family Gekkonidae with more than 140 described species (Uetz et al. 2016). While this genus naturally occurs across the tropics and subtropics, a substantial part of its distribution also results from human-mediated dispersal. Carranza Arnold (2006) retrieved five broad clades in a global phylogeny of Hemidactylus, one of which has species distributed in tropical Asia. Subsequent work by Bauer et al. (2010) and Bansal Karanth (2010) revealed that the species from tropical Asia fell into two deeply divergent and potentially non-sister sub-clades-one comprising a large radiation confined to peninsular India and Sri Lanka (the Indian radiation, IR), and the other comprising species largely distributed in Southeast (SE) Asia.

}, keywords = {Animals, India, Lizards, Phylogeny, Sri Lanka}, issn = {1175-5334}, doi = {10.11646/zootaxa.4388.1.11}, author = {Lajmi, Aparna and Datta-Roy, Aniruddha and Vyas, Raju and Agarwal, Ishan and Karanth, Praveen} } @article {31556, title = {Curvature instability of membranes near rigid inclusions.}, journal = {Phys Rev E}, volume = {97}, year = {2018}, month = {2018 Feb}, pages = {022414}, abstract = {

In multicomponent membranes, internal scalar fields may couple to membrane curvature, thus renormalizing the membrane elastic constants and destabilizing the flat membranes. Here, a general elasticity theory of membranes is considered that employs a quartic curvature expansion. The shape of the membrane and its deformation energy near a long rod-like inclusion are studied analytically. In the limit where one can neglect the end effects, the nonlinear response of the membrane to such inclusions is found in exact form. Notably, exact shape solutions are found when the membrane is curvature unstable, manifested by a negative rigidity. Near the instability point (i.e., at vanishing rigidity), the membrane is stabilized by the quartic term, giving rise to a different length scale and scale exponents for the shape and its energy profile than those found for stable membranes. The contact angle induced by an applied force at the inclusion provides a method to experimentally determine the quartic curvature modulus.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.97.022414}, author = {Rautu, S Alex} } @article {35150, title = {Defence strategies in African savanna trees.}, journal = {Oecologia}, year = {2018}, month = {2018 May 12}, abstract = {

Southern African savannas are commonly polarised into two broad types based on plant functional types and defences; infertile savannas dominated by broad-leaved trees typically defended by nitrogen-free secondary compounds and fertile savannas dominated by fine-leaved trees defended by structural defences. In this study, we use trait and other data from 15 wooded savanna sites in Southern Africa and ask if broad-leaved and fine-leaved species dominate on nutrient-poor and nutrient-rich soils, respectively. We then test if there is there any evidence for trade-offs in chemical (i.e., condensed tannins and total polyphenols) vs. structural defences on different soil types. We did not find strong evidence for a general divide in fine- vs. broad-leaved savannas according to soil fertility, nor for a simple trade-off between chemical and structural defences. Instead, we found savanna species to cluster into three broad defence strategies: species were high in leaf N and either (A) highly defended by spines and chemicals or (B) only structurally defended, or (C) low in leaf N and chemically defended. Finally, we tested for differences in browser utilisation between soil types and among plant defence strategies and found that browsing by meso-herbivores was higher on nutrient-rich soils and targeted species from groups A and B and avoided C, while browsing by elephants was mostly not affected by soil type or defence strategy. We propose a framework that can be used as a basis for asking strategic questions that will help improve our understanding of plant defences in savannas.

}, issn = {1432-1939}, doi = {10.1007/s00442-018-4165-8}, author = {Wigley, Benjamin J and Fritz, Herv{\'e} and Coetsee, Corli} } @article {49143, title = {Derivation of iPSC lines from two patients with familial Alzheimer{\textquoteright}s disease from India.}, journal = {Stem Cell Res}, volume = {34}, year = {2018}, month = {2018 Dec 19}, pages = {101370}, abstract = {

The current prevalence of diagnosable dementia in India is 1\% of people over 60 years (~3.7 million people), but is estimated to increase significantly, as ~15\% world{\textquoteright}s aged population (\>65 years) would be resident here by 2020 (Shah et al., 2016). While several mutations that pose a familial risk have been identified, the ethnic background may influence disease susceptibility, clinical presentation and treatment response. In this study, we report a detailed characterization of two representative HiPSC lines from a well-characterized dementia cohort from India. Availability of these lines, and associated molecular and clinical information, would be useful in the detailed exploration of the genomic contribution(s) to AD.

}, issn = {1876-7753}, doi = {10.1016/j.scr.2018.101370}, author = {Najar, Ashaq H and Sneha, K M and Ashok, Aparna and Babu, Swathy and Subramaniam, Anand G and Kannan, Ramkrishnan and Viswanath, Biju and Purushottam, Meera and Varghese, Mathew and Parvez, Suhel and Panicker, Mitradas M and Mukherjee, Odity and Jain, Sanjeev} } @article {45440, title = {Description and classification of Indian Ocean humpback dolphin (Sousa plumbea) whistles recorded off the Sindhudurg coast of Maharashtra, India }, journal = {Marine Mammel Science}, volume = {34}, year = {2018}, month = {07/2018}, pages = {755-776}, abstract = {

The Indian Ocean humpback dolphin (Sousa plumbea), a common cetacean species in India, has a diverse vocal repertoire, which to date has not been described in detail. This study focused on analyzing their whistle vocalizations. Humpback dolphins were recorded off the Sindhudurg coast of Maharashtra, India, and 2,260 whistles were analyzed for their acoustic characteristics. Whistles spanned a wide frequency range between 2.3 kHz and 33.0 kHz, with durations ranging from 0.01 s to 1.60 s. Whistles were categorized into seven contour classes based on their qualitative properties. A classification and regression tree (CART) analysis was used to quantify variability between the seven contour classes using the measured acoustic features. Based on the CART analysis, frequency gradient, minimum slope, maximum slope, beginning and ending slope accounted for most variability between whistle types. CART resulted in an overall classification accuracy of 89.5\%. This study provides a detailed description of acoustic features and qualitative properties of humpback dolphin whistles from the northwestern coast of India. Further comparisons of acoustic data from Sousa populations along the Indian coast are necessary to determine possible geographic variations in whistle characteristics and whether the variations are driven by environmental or genetic factors or a combination of both.

}, doi = {10.1111/mms.12479}, author = {Bopardikar, I and Sutaria, Dipani and Sule, M and Patankar, Vardhan and Klinck, H} } @article {39424, title = {Detection of cooperatively bound transcription factor pairs using ChIP-seq peak intensities and expectation maximization.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0199771}, abstract = {

Transcription factors (TFs) often work cooperatively, where the binding of one TF to DNA enhances the binding affinity of a second TF to a nearby location. Such cooperative binding is important for activating gene expression from promoters and enhancers in both prokaryotic and eukaryotic cells. Existing methods to detect cooperative binding of a TF pair rely on analyzing the sequence that is bound. We propose a method that uses, instead, only ChIP-seq peak intensities and an expectation maximization (CPI-EM) algorithm. We validate our method using ChIP-seq data from cells where one of a pair of TFs under consideration has been genetically knocked out. Our algorithm relies on our observation that cooperative TF-TF binding is correlated with weak binding of one of the TFs, which we demonstrate in a variety of cell types, including E. coli, S. cerevisiae and M. musculus cells. We show that this method performs significantly better than a predictor based only on the ChIP-seq peak distance of the TFs under consideration. This suggests that peak intensities contain information that can help detect the cooperative binding of a TF pair. CPI-EM also outperforms an existing sequence-based algorithm in detecting cooperative binding. The CPI-EM algorithm is available at https://github.com/vishakad/cpi-em.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0199771}, author = {Datta, Vishaka and Siddharthan, Rahul and Krishna, Sandeep} } @article {45436, title = {Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in-vitro culture in cryopreservation studies.}, journal = {Cryobiology}, volume = {83}, year = {2018}, month = {2018 Aug}, pages = {75-83}, abstract = {

Development of in vitro culture protocol for early stage ovarian follicles of zebrafish is important since cryopreserved early stage ovarian follicles would need to be matured in vitro following cryopreservation before they can be fertilised. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in vitro culture of early stage zebrafish ovarian follicles in ovarian tissue fragments is reported here for the first time although some work has been reported for in vitro culture of isolated early stage zebrafish ovarian follicles. The main aim of the present study was to develop molecular markers in an optimised in vitro culture protocol for stage I and stage II zebrafish ovarian follicles in ovarian tissue fragments. The effect of concentration of the hormones human chorionic gonadotropin and follicle stimulating hormones, and additives such as Foetal Bovine Serum and Bovine Serum Albumin were studied. The results showed that early stage zebrafish ovarian fragments containing stage I and stage II follicles which are cultured in vitro for 24 h in 20\% FBS and 100mIU/ml FSH in 90\% L-15 medium at 28 {\textdegree}C can grow to the size of stage II and stage III ovarian follicles respectively. More importantly the follicle growth from stage I to stage II and from stage II to stage III were confirmed using molecular markers such as cyp19a1a (also known as P450aromA) and vtg1 genes respectively. However, no follicle growth was observed following cryopreservation and in vitro culture.

}, issn = {1090-2392}, doi = {10.1016/j.cryobiol.2018.05.004}, author = {Anil, Siji and Rawson, David and Zhang, Tiantian} } @article {45454, title = {Diet Selection by the Capped Langur (Trachypithecus pileatus) in Hollongapar Gibbon Wildlife Sanctuary, Assam, North-East India }, journal = {Folia Primatologica}, volume = {89}, year = {2018}, month = {2018}, pages = {181}, author = {Kalita, U and Kumar, Ajith and Sinha, Anindya} } @article {45450, title = {Diet Selection of Leopards (Panthera pardus) in a Human-Use Landscape in North-Eastern India }, journal = { Tropical Conservation Science}, volume = {11}, year = {2018}, month = {03/2018}, abstract = {

There is increasing evidence of large carnivores using human-use areas, but our understanding of their ecology in such landscapes is limited. The role of wild and domestic prey in sustaining populations of carnivores in human-use landscapes could be significant but is currently poorly documented. We studied the prey composition and diet selection of leopards (Panthera pardus) in a forest and tea-garden landscape in north-eastern India where the population density is greater than 700 people per km2 and average domestic animal density is 340 animals per km2. Wild prey density in the landscape was 56 animals per km2. Both wild and domestic prey were used by leopards in proportion to their availability with no selectivity toward either (χ2 = 87.17, p = .99, SE = 0.001). Among wild prey, Rhesus macaque (Macaca mulatta) was found in high densities (24 animals per km2) and was preyed by leopards more frequently that the proportional availability. High use of domestic prey by leopard, with 60\% of the prey biomass comprising cattle and goats has the potential for negative impact on conservation support for the species. While on one hand, there is great scope for the persistence of large cats in dense human-use landscapes due to the availability of domestic prey, on the other hand, the study highlights the problems of livestock loss especially to poorer sections of the society which need to be reconciled for achieving long-term and sustainable conservation goals.

}, doi = {10.1177/1940082918764635}, author = {Kshettry, Aritra and Vaidyanathan, S. and Athreya, Vidya} } @article {35861, title = {Dietary and developmental shifts in butterfly-associated bacterial communities.}, journal = {R Soc Open Sci}, volume = {5}, year = {2018}, month = {2018 May}, pages = {171559}, abstract = {

Bacterial communities associated with insects can substantially influence host ecology, evolution and behaviour. Host diet is a key factor that shapes bacterial communities, but the impact of dietary transitions across insect development is poorly understood. We analysed bacterial communities of 12 butterfly species across different developmental stages, using amplicon sequencing of the 16S rRNA gene. Butterfly larvae typically consume leaves of a single host plant, whereas adults are more generalist nectar feeders. Thus, we expected bacterial communities to vary substantially across butterfly development. Surprisingly, only few species showed significant dietary and developmental transitions in bacterial communities, suggesting weak impacts of dietary transitions across butterfly development. On the other hand, bacterial communities were strongly influenced by butterfly species and family identity, potentially due to dietary and physiological variation across the host phylogeny. Larvae of most butterfly species largely mirrored bacterial community composition of their diets, suggesting passive acquisition rather than active selection. Overall, our results suggest that although butterflies harbour distinct microbiomes across taxonomic groups and dietary guilds, the dramatic dietary shifts that occur during development do not impose strong selection to maintain distinct bacterial communities across all butterfly hosts.

}, issn = {2054-5703}, doi = {10.1098/rsos.171559}, author = {Phalnikar, Kruttika and Kunte, Krushnamegh and Agashe, Deepa} } @article {43848, title = {Differences in spatial resolution and contrast sensitivity of flight control in the honeybees and .}, journal = {J Exp Biol}, year = {2018}, month = {2018 Aug 20}, abstract = {

Visually-guided behaviour is constrained by the capacity of the visual system to resolve detail. This is, in turn, limited by the spatial resolution and contrast sensitivity of the underlying visual system. Because these properties are interdependent and vary non-uniformly, it is only possible to fully understand the limits of a specific visually guided behaviour when they are investigated in combination. To understand the visual limits of flight control in bees, which rely heavily on vision to control flight, and to explore whether they vary between species, we tested how changes in spatial resolution and contrast sensitivity affect the speed and position control of the Asian and European honeybees ( and ). Despite their apparent similarity, we found some interesting and surprising differences between the visual limits of these species. While the effect of spatial frequency and contrast on position control is similar between the species, ground speed is differently affected by these variables. A comparison with published data from the bumblebee reveals further differences. The visual resolution that limits the detection and use of optic flow for flight control in both species of honeybees is lower than previously anatomically determined resolution and differs from object detection limits of , providing evidence that the limits of spatial resolution and contrast sensitivity are highly tuned to the particular behavioural task of a species.

}, issn = {1477-9145}, doi = {10.1242/jeb.184267}, author = {Chakravarthi, Aravin and Rajus, Santosh and Kelber, Almut and Dacke, Marie and Baird, Emily} } @article {33717, title = {Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science.}, journal = {BMC Psychiatry}, volume = {18}, year = {2018}, month = {2018 Apr 18}, pages = {106}, abstract = {

BACKGROUND: There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer{\textquoteright}s dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository.

METHODS: The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing.

DISCUSSION: We hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

}, issn = {1471-244X}, doi = {10.1186/s12888-018-1674-2}, author = {Viswanath, Biju and Rao, Naren P and Narayanaswamy, Janardhanan C and Sivakumar, Palanimuthu T and Kandasamy, Arun and Kesavan, Muralidharan and Mehta, Urvakhsh Meherwan and Venkatasubramanian, Ganesan and John, John P and Mukherjee, Odity and Purushottam, Meera and Kannan, Ramakrishnan and Mehta, Bhupesh and Kandavel, Thennarasu and Binukumar, B and Saini, Jitender and Jayarajan, Deepak and Shyamsundar, A and Moirangthem, Sydney and Vijay Kumar, K G and Thirthalli, Jagadisha and Chandra, Prabha S and Gangadhar, Bangalore N and Murthy, Pratima and Panicker, Mitradas M and Bhalla, Upinder S and Chattarji, Sumantra and Benegal, Vivek and Varghese, Mathew and Reddy, Janardhan Y C and Raghu, Padinjat and Rao, Mahendra and Jain, Sanjeev} } @article {43840, title = {Divergent early mesoderm specification underlies distinct head and trunk muscle programmes in vertebrates.}, journal = {Development}, volume = {145}, year = {2018}, month = {2018 Sep 20}, abstract = {

Head and trunk muscles have discrete embryological origins and are governed by distinct regulatory programmes. Whereas the developmental route of trunk muscles from mesoderm is well studied, that of head muscles is ill defined. Here, we show that, unlike the myogenic trunk paraxial mesoderm, head mesoderm development is independent of the T/Tbx6 network in mouse. We reveal that, in contrast to Wnt and FGF-driven trunk mesoderm, dual inhibition of Wnt/β-catenin and Nodal specifies head mesoderm. Remarkably, the progenitors derived from embryonic stem cells by dual inhibition efficiently differentiate into cardiac and skeletal muscle cells. This twin potential is the defining feature of cardiopharyngeal mesoderm: the head subtype giving rise to heart and branchiomeric head muscles. Therefore, our findings provide compelling evidence that dual inhibition specifies head mesoderm and unravel the mechanism that diversifies head and trunk muscle programmes during early mesoderm fate commitment. Significantly, this is the first report of directed differentiation of pluripotent stem cells, without transgenes, into progenitors with muscle/heart dual potential. Ability to generate branchiomeric muscle could catalyse efforts in modelling myopathies that selectively involve head muscles.

}, issn = {1477-9129}, doi = {10.1242/dev.160945}, author = {Nandkishore, Nitya and Vyas, Bhakti and Javali, Alok and Ghosh, Subho and Sambasivan, Ramkumar} } @article {36260, title = {Diversity, Stability, and Reproducibility in Stochastically Assembled Microbial Ecosystems.}, journal = {Phys Rev Lett}, volume = {120}, year = {2018}, month = {2018 Apr 13}, pages = {158102}, abstract = {

Microbial ecosystems are remarkably diverse, stable, and usually consist of a mixture of core and peripheral species. Here we propose a conceptual model exhibiting all these emergent properties in quantitative agreement with real ecosystem data, specifically species abundance and prevalence distributions. Resource competition and metabolic commensalism drive the stochastic ecosystem assembly in our model. We demonstrate that even when supplied with just one resource, ecosystems can exhibit high diversity, increasing stability, and partial reproducibility between samples.

}, keywords = {Ecosystem, Microbiota, Models, Biological, Stochastic Processes}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.120.158102}, author = {Goyal, Akshit and Maslov, Sergei} } @article {38422, title = {Dry season diet composition of four-horned antelope in tropical dry deciduous forests, Nepal.}, journal = {PeerJ}, volume = {6}, year = {2018}, month = {2018}, pages = {e5102}, abstract = {

It is essential to assess the feeding strategies of threatened species during resource-scarce seasons to understand their dietary niche breadth and inform appropriate habitat management measures. In this study, we examined the diet composition of four-horned antelope (FHA) and , one of the least studied ungulate species, in Banke National Park, Nepal. A total of 53 fresh pellet groups were collected between December 2015 and January 2016 and analyzed using micro-histological fecal analysis technique. First, we prepared 133 micro-histological photographs of different parts of 64 reference plant species. Then we compared 1,590 fragments of 53 fecal samples with photographs of reference plants to assess the percentage of occurrence of different plant species in FHA diet. A total of 30 plant species belonging to 18 different families were identified in fecal samples. Chi-square goodness of fit tests showed that FHA appeared not to feed all plant uniformly. Out of 1,520 identified fragments in fecal samples, 1,300 were browse species and 220 were grass species. Browse represented 85.5\% of the identified plant fragments, suggesting that FHA might be adopting a browser strategy at least during winter when grasses are low in abundance and their nutritive quality is poor. Tree species had the highest contribution in the diet (46.55\%) followed by shrubs (24.52\%). The family Gramineae was consumed in the highest proportion (27.68\%) followed by Euphorbiaceae (11.95\%). Overall, our results suggest that FHA has the feeding plasticity to adapt to resource fluctuation. Based on the findings of this study, we recommend that dicot plant species-particularly fruit trees and shrubs, which are the major source of nutrients for FHA during resource-lean, dry season-be conserved and natural regeneration of these taxa be promoted.

}, issn = {2167-8359}, doi = {10.7717/peerj.5102}, author = {Oli, Chet Bahadur and Panthi, Saroj and Subedi, Naresh and Ale, Gagan and Pant, Ganesh and Khanal, Gopal and Bhattarai, Suman} } @article {36657, title = {dSTIM- and Ral/Exocyst-Mediated Synaptic Release from Pupal Dopaminergic Neurons Sustains Flight.}, journal = {eNeuro}, volume = {5}, year = {2018}, month = {2018 May-Jun}, abstract = {

Manifestation of appropriate behavior in adult animals requires developmental mechanisms that help in the formation of correctly wired neural circuits. Flight circuit development in requires store-operated calcium entry (SOCE) through the STIM/Orai pathway. SOCE-associated flight deficits in adult derive extensively from regulation of gene expression in pupal neurons, and one such SOCE-regulated gene encodes the small GTPase . The cellular mechanism by which Ral helps in maturation of the flight circuit was not understood. Here, we show that knockdown of components of a Ral effector, the exocyst complex, in pupal neurons also leads to reduced flight bout durations, and this phenotype derives primarily from dopaminergic neurons. Importantly, synaptic release from pupal dopaminergic neurons is abrogated upon knockdown of dSTIM, Ral, or exocyst components. overexpression restores the diminished synaptic release of knockdown neurons as well as flight deficits associated with knockdown in dopaminergic neurons. These results identify Ral-mediated vesicular release as an effector mechanism of neuronal SOCE in pupal dopaminergic neurons with functional consequences on flight behavior.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0455-17.2018}, author = {Richhariya, Shlesha and Jayakumar, Siddharth and Kumar Sukumar, Sanjay and Hasan, Gaiti} } @article {45437, title = {Editorial Overview: Membranes and organelles: rethinking membrane structure, function and compartments.}, journal = {Curr Opin Cell Biol}, volume = {53}, year = {2018}, month = {2018 Aug}, pages = {A1-A3}, issn = {1879-0410}, doi = {10.1016/j.ceb.2018.07.005}, author = {Spang, Anne and Mayor, Satyajit} } @article {45434, title = {Effects of increased N and P availability on biomass allocation and root carbohydrate reserves differ between N-fixing and non-N-fixing savanna tree seedlings.}, journal = {Ecol Evol}, volume = {8}, year = {2018}, month = {2018 Aug}, pages = {8467-8476}, abstract = {

In mixed tree-grass ecosystems, tree recruitment is limited by demographic bottlenecks to seedling establishment arising from inter- and intra-life-form competition, and disturbances such as fire. Enhanced nutrient availability resulting from anthropogenic nitrogen (N) and phosphorus (P) deposition can alter the nature of these bottlenecks by changing seedling growth and biomass allocation patterns, and lead to longer-term shifts in tree community composition if different plant functional groups respond differently to increased nutrient availability. However, the extent to which tree functional types characteristic of savannas differ in their responses to increased N and P availability remains unclear. We quantified differences in above- and belowground biomass, and root carbohydrate contents in seedlings of multiple N-fixing and non-N-fixing tree species characteristic of Indian savanna and dry forest ecosystems in response to experimental N and P additions. These parameters are known to influence the ability of plants to compete, as well as survive and recover from fires. N-fixers in our study were co-limited by N and P availability, while non-N-fixers were N limited. Although both functional groups increased biomass production following fertilization, non-N-fixers were more responsive and showed greater relative increases in biomass with fertilization than N-fixers. N-fixers had greater baseline investment in belowground resources and root carbohydrate stocks, and while fertilization reduced root:shoot ratios in both functional groups, root carbohydrate content only reduced with fertilization in non-N-fixers. Our results indicate that, even within a given system, plants belonging to different functional groups can be limited by, and respond differentially to, different nutrients, suggesting that long-term consequences of nutrient deposition are likely to vary across savannas contingent on the relative amounts of N and P being deposited in sites.

}, issn = {2045-7758}, doi = {10.1002/ece3.4289}, author = {Varma, Varun and Catherin, Arockia M and Sankaran, Mahesh} } @article {49277, title = {Energy Landscape of the Designed Protein Top7.}, journal = {J Phys Chem B}, year = {2018}, month = {2018 Nov 29}, abstract = {

To fold on biologically relevant timescales, proteins have evolved funnelled energy landscapes with minimal energetic trapping. However, the polymeric nature of proteins and the spatial arrangement of secondary structural elements can create topological traps and slow folding. It is challenging to identify, visualise and quantify such topological trapping. Designed proteins have not had the benefit of evolution and it has been hypothesised that de novo designed protein topologies may therefore feature more topological trapping. Structure-based models (SBMs) are inherently funnelled and remove most energetic trapping and can thus be used to isolate the effect of protein topology on the folding energy landscape. Here, we compare properties of the potential energy landscapes (PEL) of Top7, a designed protein with a topology unknown in nature, with those of S6, a naturally occurring ribosomal protein of similar size and topology. Possible kinetic traps and the energetic barriers separating them from the native state are elucidated. We find that even with an SBM, the PEL of the designed protein is more frustrated than that of the natural protein. We then quantify the effect of adding non-native hydrophobic interactions and coarse-grained side-chains through a frustration density parameter. A clear increase in frustration is observed on including side-chains, whereas adding hydrophobic interactions leads to a narrowing of the funnel and a decrease in complexity. The most likely (un)folding routes for all models are derived through the construction of "probability contact maps". The ability to quantitatively understand and optimise the organisation of the PEL for designed proteins may enable us to sculpt structure-seeking landscapes, mimicking the effect of evolution.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.8b08499}, author = {Neelamraju, Sridhar and Gosavi, Shachi and Wales, David J} } @article {36666, title = {Evaluating Ylehd, a recombinant epoxide hydrolase from Yarrowia lipolytica as a potential biocatalyst for the resolution of benzyl glycidyl ether}, journal = {RSC ADVANCES}, volume = {8}, year = {2018}, month = {2018}, pages = {12918-12926}, doi = {10.1039/c8ra00628h}, author = {Bendigiri, C and Harini, K and Yenkar, S and Zinjarde, S and Sowdhamini, R and RaviKumar, A} } @article {30018, title = {Evidence of sinks and sources in the phospholipase C activated PIP2 cycle.}, journal = {FEBS Lett}, year = {2018}, month = {2018 Feb 10}, abstract = {

In many eukaryotic signalling cascades, receptor mediated phospholipase C (PLC) activity triggers phosphatidylinositol-4,5-bisphosphate (PIP2 ) hydrolysis leading to information transfer. Coupled with PLC activation is a sequence of reactions spread across multiple compartments which resynthesize PIP2 , a process essential for supporting sustained PLC signalling. The biochemical strategies coordinating these reactions and, in particular, whether this is a closed cycle with no net addition or loss of metabolites, are poorly understood. Using mathematical models, we find that most closed PIP2 cycles cannot explain experimentally observed changes in key metabolic intermediates in particular mutants. Thus, we propose that the PIP2 cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway. This article is protected by copyright. All rights reserved.

}, issn = {1873-3468}, doi = {10.1002/1873-3468.12998}, author = {Suratekar, Rohit and Panda, Aniruddha and Padinjat, Raghu and Krishna, Sandeep} } @article {36105, title = {Experiential contributions to social dominance in a rat model of fragile-X syndrome.}, journal = {Proc Biol Sci}, volume = {285}, year = {2018}, month = {2018 Jun 13}, abstract = {

Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a {\textquoteright}knockout{\textquoteright} rat model of fragile-X, we examined whether deletion of the gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X {\textquoteright}knockout{\textquoteright} rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.

}, issn = {1471-2954}, doi = {10.1098/rspb.2018.0294}, author = {Saxena, K and Webster, J and Hallas-Potts, A and Mackenzie, R and Spooner, P A and Thomson, D and Kind, P and Chatterji, S and Morris, R G M} } @article {27273, title = {Exploring the effects of sparse restraints on protein structure prediction.}, journal = {Proteins}, volume = {86}, year = {2018}, month = {02/2018}, pages = {248-262}, abstract = {

One of the main barriers to accurate computational protein structure prediction is searching the vast space of protein conformations. Distance restraints or inter-residue contacts have been used to reduce this search space, easing the discovery of the correct folded state. It has been suggested that about one contact for every twelve residues may be sufficient to predict structure at fold level accuracy. Here, we use coarse-grained structure-based models in conjunction with molecular dynamics simulations to examine this empirical prediction. We generate sparse contact maps for 15 proteins of varying sequence lengths and topologies and find that given perfect secondary-structural information, a small fraction of the native contact map (5-10\%) suffices to fold proteins to their correct native states. We also find that different sparse maps are not equivalent and we make several observations about the type of maps that are successful at such structure prediction. Long range contacts are found to encode more information than shorter range ones, especially for α and αβ-proteins. However, this distinction reduces for β-proteins. Choosing contacts that are a consensus from successful maps gives predictive sparse maps as does choosing contacts that are well spread out over the protein structure. Additionally, the folding of proteins can also be used to choose predictive sparse maps. Overall, we conclude that structure-based models can be used to understand the efficacy of structure-prediction restraints and could, in future, be tuned to include specific force-field interactions, secondary structure errors and noise in the sparse maps. This article is protected by copyright. All rights reserved.

}, issn = {1097-0134}, doi = {10.1002/prot.25438}, author = {Mandalaparthy, Varun and Sanaboyana, Venkata Ramana and Rafalia, Hitesh and Gosavi, Shachi} } @article {43851, title = {Extinction recall of fear memories formed before stress is not affected despite higher theta activity in the amygdala.}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 Aug 13}, abstract = {

Stress is known to exert its detrimental effects not only by enhancing fear, but also by impairing its extinction. However, in earlier studies stress exposure preceded both processes. Thus, compared to unstressed animals, stressed animals had to extinguish fear memories that were strengthened by prior exposure to stress. Here, we dissociate the two processes to examine if stress specifically impairs the acquisition and recall of fear extinction. Strikingly, when fear memories were formed before stress exposure, thereby allowing animals to initiate extinction from comparable levels of fear, recall of fear extinction was unaffected. Despite this, we observed a persistent increase in theta activity in the BLA. Theta activity in the mPFC, by contrast, was normal. Stress also disrupted mPFC-BLA theta-frequency synchrony and directional coupling. Thus, in the absence of the fear-enhancing effects of stress, the expression of fear during and after extinction reflects normal regulation of theta activity in the mPFC, not theta hyperactivity in the amygdala.

}, issn = {2050-084X}, doi = {10.7554/eLife.35450}, author = {Rahman, Mohammed Mostafizur and Shukla, Ashutosh and Chattarji, Sumantra} } @article {48893, title = {Fairyflies.}, journal = {Curr Biol}, volume = {28}, year = {2018}, month = {2018 Dec 03}, pages = {R1331-R1332}, abstract = {

A Quick Guide to fairyflies, miniature parasitoid wasps which have the smallest adult size known for any insect.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2018.10.014}, author = {Palavalli-Nettimi, Ravindra and Sane, Sanjay P} } @article {45309, title = {Feedbacks from the metabolic network to the genetic network reveal regulatory modules in E. coli and B. subtilis.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0203311}, abstract = {

The genetic regulatory network (GRN) plays a key role in controlling the response of the cell to changes in the environment. Although the structure of GRNs has been the subject of many studies, their large scale structure in the light of feedbacks from the metabolic network (MN) has received relatively little attention. Here we study the causal structure of the GRNs, namely the chain of influence of one component on the other, taking into account feedback from the MN. First we consider the GRNs of E. coli and B. subtilis without feedback from MN and illustrate their causal structure. Next we augment the GRNs with feedback from their respective MNs by including (a) links from genes coding for enzymes to metabolites produced or consumed in reactions catalyzed by those enzymes and (b) links from metabolites to genes coding for transcription factors whose transcriptional activity the metabolites alter by binding to them. We find that the inclusion of feedback from MN into GRN significantly affects its causal structure, in particular the number of levels and relative positions of nodes in the hierarchy, and the number and size of the strongly connected components (SCCs). We then study the functional significance of the SCCs. For this we identify condition specific feedbacks from the MN into the GRN by retaining only those enzymes that are essential for growth in specific environmental conditions simulated via the technique of flux balance analysis (FBA). We find that the SCCs of the GRN augmented by these feedbacks can be ascribed specific functional roles in the organism. Our algorithmic approach thus reveals relatively autonomous subsystems with specific functionality, or regulatory modules in the organism. This automated approach could be useful in identifying biologically relevant modules in other organisms for which network data is available, but whose biology is less well studied.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0203311}, author = {Kumar, Santhust and Mahajan, Saurabh and Jain, Sanjay} } @article {30078, title = { Female butterflies modulate investment in reproduction and flight in response to monsoon-driven migrations}, journal = {OIKOS}, volume = { 127 }, year = {2018}, month = {02/2018}, pages = {285-296}, abstract = {
Migratory species may display striking phenotypic plasticity during individual lifetimes. This may include differential investment in body parts and functions, differential resource use and allocation, and behavioural changes between migratory and non-migratory phases. While migration-related phenotypic changes are well-reported, their underlying mechanisms are usually poorly understood. Here we compare individuals from migratory (reproductive diapause) and non-migratory (reproductive) phases of closely related aposematic butterfly species to study how sexual dimorphism and migratory behaviour underlie significant morphological tradeoffs, and propose a plausible scenario to explain the migration-related phenotypic plasticity observed in females of migratory species. We found that female butterflies invested significantly more in their abdominal mass compared to males irrespective of their migratory phase, and underwent a clear shift in their body mass allocation after the switch from the reproductive diapause phase to the reproductive phase. In reproductive phase, females invested much more in reproductive tissue. This switch occurred as a result of increased abdominal mass (i.e. reproductive tissue mass) without significant reduction in the thoracic mass (i.e. flight muscle mass). Migratory males, however, were not significantly different from non-migratory males in terms of relative investment in flight and reproductive tissues. These patterns were consistent between migratory and non-migratory aposematic species within and across clades. While migratory habits may influence the physiology and behaviour of both sexes, long-distance migration affected female morphology much more markedly compared to that of males. These results show the sex-specific nature of adaptations to migratory behaviour, and suggest that seemingly disparate life-history traits such as aposematism and migration may have similar influences on the lifetime energetic investments of insects.

}, doi = {10.1111/oik.04593}, author = {Bhaumik, V. and Kunte, Krushnamegh} } @article {27663, title = {Female Density-Dependent Chemical Warfare Underlies Fitness Effects of Group Sex Ratio in Flour Beetles}, journal = {American Naturalist}, year = {2018}, month = {12/2017}, abstract = {

In animals, skewed sex ratios can affect individual fitness via sexual (e.g., intersexual conflict or intrasexual mate competition) or nonsexual (e.g., sex-specific resource competition) interactions. Because most analyses of sex ratio focus on sexual interactions, the relative importance of sexual versus nonsexual mechanisms remains unclear. We tested both mechanisms in the flour beetle Tribolium castaneum, where male-biased sex ratios increase female fitness relative to unbiased or female-biased groups. Although flour beetles show both sexual and nonsexual (resource) competition, we found that sexual interactions did not explain female fitness. Instead, female fecundity was dramatically reduced even after a brief exposure to flour conditioned by other females. Earlier studies suggested that secreted toxins might mediate density-dependent population growth in flour beetles. We identified ethyl benzoquinone and methyl benzoquinone (quinones) as components of adult stink glands that regulate female fecundity. In female-biased groups (i.e., at high female density), females upregulated quinones and suppressed each other{\textquoteright}s reproduction. In male-biased groups, low female density and associated low quinone levels maximized fecundity. Thus, females appear to use quinones as weapons for female-specific, density-dependent interference competition. Our results underscore the importance of nonsexual interference competition that may often underlie the fitness consequences of skewed sex ratios.

}, doi = {10.1086/695806}, author = {Khan, Imroze and Prakash, Arun and Issar, Swastika and Umarani, Mihir and Sasidharan, Rohit and Masagalli, JN and Lama, Prakash and Venkatesan, Radhika and Agashe, Deepa} } @article {43856, title = {FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.}, journal = {Proc Natl Acad Sci U S A}, volume = {115}, year = {2018}, month = {2018 08 14}, pages = {8388-8393}, abstract = {

The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections known as stereocilia. Hair bundle polarity depends on kinociliary protocadherin-15 (Pcdh15) localization. Protocadherin-15 is found only in hair-cell kinocilia, and is not localized to the primary cilia of adjacent supporting cells. Thus, Pcdh15 must be specifically targeted and trafficked into the hair-cell kinocilium. Here we show that kinocilial Pcdh15 trafficking relies on cell type-specific coupling to the generic intraflagellar transport (IFT) transport mechanism. We uncover a role for fibroblast growth factor receptor 1 (FGFR1) in loading Pcdh15 onto kinociliary transport particles in hair cells. We find that on activation, FGFR1 binds and phosphorylates Pcdh15. Moreover, we find a previously uncharacterized role for clathrin in coupling this kinocilia-specific cargo with the anterograde IFT-B complex through the adaptor, DAB2. Our results identify a modified ciliary transport pathway used for Pcdh15 transport into the cilium of the inner ear hair cell and coordinated by FGFR1 activity.

}, keywords = {Adaptor Proteins, Vesicular Transport, Animals, Cadherins, Chick Embryo, Clathrin, Flagella, Hair Cells, Auditory, Inner, Mice, Phosphorylation, Protein Precursors, Protein Transport, Receptor, Fibroblast Growth Factor, Type 1}, issn = {1091-6490}, doi = {10.1073/pnas.1719861115}, author = {Honda, Akira and Kita, Tomoko and Seshadri, Shri Vidhya and Misaki, Kazuyo and Ahmed, Zamal and Ladbury, John E and Richardson, Guy P and Yonemura, Shigenobu and Ladher, Raj K} } @article {39426, title = {FindSim: A Framework for Integrating Neuronal Data and Signaling Models.}, journal = {Front Neuroinform}, volume = {12}, year = {2018}, month = {2018}, pages = {38}, abstract = {

Current experiments touch only small but overlapping parts of very complex subcellular signaling networks in neurons. Even with modern optical reporters and pharmacological manipulations, a given experiment can only monitor and control a very small subset of the diverse, multiscale processes of neuronal signaling. We have developed FindSim (Framework for Integrating Neuronal Data and SIgnaling Models) to anchor models to structured experimental datasets. FindSim is a framework for integrating many individual electrophysiological and biochemical experiments with large, multiscale models so as to systematically refine and validate the model. We use a structured format for encoding the conditions of many standard physiological and pharmacological experiments, specifying which parts of the model are involved, and comparing experiment outcomes with model output. A database of such experiments is run against successive generations of composite cellular models to iteratively improve the model against each experiment, while retaining global model validity. We suggest that this toolchain provides a principled and scalable way to tackle model complexity and diversity of data sources.

}, issn = {1662-5196}, doi = {10.3389/fninf.2018.00038}, author = {Viswan, Nisha A and HarshaRani, Gubbi Vani and Stefan, Melanie I and Bhalla, Upinder S} } @article {43854, title = {First appearance deceives many: disentangling the species complex using an integrated approach.}, journal = {PeerJ}, volume = {6}, year = {2018}, month = {2018}, pages = {e5341}, abstract = {

The gekkonid lizard genus Oken is the second most species-rich genus of geckos with greatest diversity in the tropical regions of the world. Some species of the genus are commensal and widespread; however, there are several endemic lineages with restricted distribution. India is home to at least 35 species, with 20 endemic species and the number is steadily increasing with exploration of new habitats and integrated taxonomic approach including molecular data. We made investigations into the molecular and morphological variation throughout the distribution of Daudin, 1802 based on fresh specimens, literature review, museum material and molecular data. Results from morphological, molecular and micro-CT based anatomical data are unequivocal and show that is a species complex represented by three species, sensu stricto and two undescribed taxa. Jerdon, 1854 syn. nov. was found to be morphologically similar to the type specimen of , and genetically embedded in a clade containing sensu stricto and is here treated as a junior synonym of , whereas Deraniyagala is referred to as given that the types are presently not traceable and the original description is inadequate in diagnosing the taxon. The populations from western-central India and parts of Pakistan, and from southern Karnataka are distinct and diagnosable, and are herein described as two new species, respectively. Morphological and molecular data support the distinctiveness of the new species. The present work resolves a taxonomic turmoil that lasted over two centuries highlighting the need for studies that integrate morphological and molecular data.

}, issn = {2167-8359}, doi = {10.7717/peerj.5341}, author = {Mirza, Zeeshan A and Gowande, Gaurang G and Patil, Rishikesh and Ambekar, Mayuresh and Patel, Harshil} } @article {45533, title = {First description of the female of Chrysilla volupe (Karsch, 1879) (Araneae: Salticidae: Chrysillini) from India, with notes on the species{\textquoteright} distribution and life history}, journal = {Arthropoda Selecta}, volume = {27}, year = {2018}, month = {06/2018}, pages = {143-153}, abstract = {

Chrysilla volupe (Karsch, 1879) is redescribed based on fresh materials collected from India. The female is described for the first time. Observations on the initial developmental stages of the eggs and the first instar are documented. A map showing the refined distributional range of C. volupe is provided. A new combination is proposed for the African species, Chrysilla guineensis (Weso{\l}owska et Wi{\'s}niewski, 2013) comb.n. (ex. Phintella), thereby confirming the occurrence of the genus in the Afrotropical Region.

}, doi = {10.15298/arthsel.27.2.06}, author = {Caleb, JTD and Sanap, R.V. and Patel, KG and Sudhikumar, AV} } @article {45435, title = {Fish community responses to stream flow alterations and habitat modifications by small hydropower projects in the Western Ghats biodiversity hotspot, India}, journal = {Aquatic Conservation: Marine and Freshwater Ecosystems}, volume = {28}, year = {2018}, month = {08/2018}, pages = {9792-993}, abstract = {
  1. Small hydropower projects (SHPs) are promoted as environmentally benign alternatives to larger dams; however, the impacts of SHPs have been poorly studied, especially in tropical developing countries, where their growth is being encouraged.
  2. This study assessed the impacts of two SHPs on freshwater fish communities in the Western Ghats biodiversity hotspot of India. Two dammed and one undammed tributary of the Netravathi River, having similar stream order, elevation, and surrounding land-use types, were identified as test and control sites respectively. Stream geometry, water chemistry, and fish assemblages were compared across upstream, dewatered, and downstream location categories within and across the three streams.
  3. Flow alterations induced by SHPs affected the dewatered river stretches most severely. Stream wetted width and depths diminished drastically in dammed dewatered segments, and consequently this region was characterized by elevated water temperature and reduced dissolved oxygen.
  4. Fish species composition varied significantly between dammed and undammed sites, across the upstream, dewatered, and downstream location categories. Dammed segments had lower fish species richness, diversity, and endemicity, and were dominated by eurytopic species (adapted to lentic conditions), unlike the control site, which was dominated by rheophilic species (adapted to flowing waters). Regression analyses indicated that fish species richness in dammed streams increased with distance from the dam in the upstream direction.
  5. The SHPs were found to have severe impacts on stream geometry, water chemistry, and aquatic biota, especially in the dry season.
  6. Given the ambitious targets of planned SHP growth, most of which are within ecologically fragile regions, changes in SHP operations and policies are proposed to enable the conservation of river fish diversity. These include mandatory environmental impact assessments, conserving undammed headwater streams in regulated basins, maintaining adequate environmental flows, and implementing other mitigation measures.
}, doi = {10.1002/aqc.2904}, author = {Jumani, Suman and Rao, Shishir and Kelkar, Nachiket} } @article {34069, title = {Flow-induced phase separation of active particles is controlled by boundary conditions.}, journal = {Proc Natl Acad Sci U S A}, year = {2018}, month = {2018 May 07}, abstract = {

Active particles, including swimming microorganisms, autophoretic colloids, and droplets, are known to self-organize into ordered structures at fluid-solid boundaries. The entrainment of particles in the attractive parts of their spontaneous flows has been postulated as a possible mechanism underlying this phenomenon. Here, combining experiments, theory, and numerical simulations, we demonstrate the validity of this flow-induced ordering mechanism in a suspension of active emulsion droplets. We show that the mechanism can be controlled, with a variety of resultant ordered structures, by simply altering hydrodynamic boundary conditions. Thus, for flow in Hele-Shaw cells, metastable lines or stable traveling bands can be obtained by varying the cell height. Similarly, for flow bounded by a plane, dynamic crystallites are formed. At a no-slip wall, the crystallites are characterized by a continuous out-of-plane flux of particles that circulate and re-enter at the crystallite edges, thereby stabilizing them. At an interface where the tangential stress vanishes, the crystallites are strictly 2D, with no out-of-plane flux. We rationalize these experimental results by calculating, in each case, the slow viscous flow produced by the droplets and the long-ranged, many-body active forces and torques between them. The results of numerical simulations of motion under the action of the active forces and torques are in excellent agreement with experiments. Our work elucidates the mechanism of flow-induced phase separation in active fluids, particularly active colloidal suspensions, and demonstrates its control by boundaries, suggesting routes to geometric and topological phenomena in an active matter.

}, issn = {1091-6490}, doi = {10.1073/pnas.1718807115}, author = {Thutupalli, Shashi and Geyer, Delphine and Singh, Rajesh and Adhikari, Ronojoy and Stone, Howard A} } @article {28565, title = {Fluid flow modulates electrical activity in cardiac hERG potassium channels.}, journal = {J Biol Chem}, year = {2018}, month = {2018 Jan 05}, abstract = {

Fluid movement within the heart generates substantial shear forces, but the effect of this mechanical stress on the electrical activity of the human heart has not been examined. The fast component of the delayed rectifier potassium currents responsible for repolarization of the cardiac action potential, Ikr, is encoded by the hERG channel. Here, we exposed hERG1a channel-expressing HEK293T cells to laminar shear stress (LSS) and observed that this mechanical stress increased the whole-cell current by 30\%-40\%. LSS shifted the voltage dependence of steady-state activation of the hERG\  channel to the hyperpolarizing direction, accelerated the time course of activation and recovery from inactivation, slowed down deactivation, and shifted the steady-state inactivation to the positive direction, all of which favored the hERG open state. In contrast, the time course of inactivation was faster, favoring the closed state. Using specific inhibitors of focal adhesion kinase (FAK), a regulator of mechano-transduction via the integrin pathway, we also found that the LSS-induced modulation of the whole-cell current depended on the integrin pathway. The hERG1b channel variant, which lacks the Per-Arnt-Sim (PAS) domain, and long QT syndrome-associated variants having point mutations in the PAS domain were unaffected by LSS, suggesting that the PAS domain in hERG1a channel may be involved in sensing mechanical shear stress. We conclude that a mechano-electric feedback pathway modulates hERG channel activity through the integrin pathway, indicating that mechanical forces in the heart influence its electrical activity.

}, issn = {1083-351X}, doi = {10.1074/jbc.RA117.000432}, author = {Roy, Samrat and Mathew, M K} } @article {43850, title = {FMRFa receptor stimulated Ca2+ signals alter the activity of flight modulating central dopaminergic neurons in Drosophila melanogaster.}, journal = {PLoS Genet}, volume = {14}, year = {2018}, month = {2018 Aug}, pages = {e1007459}, abstract = {

Neuropeptide signaling influences animal behavior by modulating neuronal activity and thus altering circuit dynamics. Insect flight is a key innate behavior that very likely requires robust neuromodulation. Cellular and molecular components that help modulate flight behavior are therefore of interest and require investigation. In a genetic RNAi screen for G-protein coupled receptors that regulate flight bout durations, we earlier identified several receptors, including the receptor for the neuropeptide FMRFa (FMRFaR). To further investigate modulation of insect flight by FMRFa we generated CRISPR-Cas9 mutants in the gene encoding the Drosophila FMRFaR. The mutants exhibit significant flight deficits with a focus in dopaminergic cells. Expression of a receptor specific RNAi in adult central dopaminergic neurons resulted in progressive loss of sustained flight. Further, genetic and cellular assays demonstrated that FMRFaR stimulates intracellular calcium signaling through the IP3R and helps maintain neuronal excitability in a subset of dopaminergic neurons for positive modulation of flight bout durations.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1007459}, author = {Ravi, Preethi and Trivedi, Deepti and Hasan, Gaiti} } @article {47057, title = {FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation.}, journal = {iScience}, volume = {9}, year = {2018}, month = {2018 Nov 07}, pages = {399-411}, abstract = {

FMRP is an RNA-binding protein that is known to localize in the cytoplasm and in the nucleus. Here, we have identified an interaction of FMRP with a specific set of C/D box snoRNAs in the nucleus. C/D box snoRNAs guide 2{\textquoteright}O methylations of ribosomal RNA (rRNA) on defined sites, and this modification regulates rRNA folding and assembly of ribosomes. 2{\textquoteright}O methylation of rRNA is partial on several sites in human embryonic stem cells, which results in ribosomes with differential methylation patterns. FMRP-snoRNA interaction affects rRNA methylation on several of these sites, and in the absence of FMRP, differential methylation pattern of rRNA is significantly altered. We found that FMRP recognizes ribosomes carrying specific methylation patterns on rRNA and the recognition of methylation pattern by FMRP may potentially determine the translation status of its target mRNAs. Thus, FMRP integrates its function in the nucleus and in the cytoplasm.

}, issn = {2589-0042}, doi = {10.1016/j.isci.2018.11.007}, author = {D{\textquoteright}Souza, Michelle Ninochka and Gowda, Naveen Kumar Chandappa and Tiwari, Vishal and Babu, Rosana Ottakandathil and Anand, Praveen and Dastidar, Sudhriti Ghosh and Singh, Randhir and Selvaraja, Bhuvaneish and Pal, Rakhi and Ramesh, Arati and Chattarji, Sumantra and Chandran, Siddharthan and Gulyani, Akash and Palakodeti, Dasaradhi and Muddashetty, Ravi S} } @article {29624, title = {On the folding of a structurally complex protein to its metastable active state.}, journal = {Proc Natl Acad Sci U S A}, year = {2018}, month = {2018 Jan 17}, abstract = {

For successful protease inhibition, the reactive center loop (RCL) of the two-domain serine protease inhibitor, α1-antitrypsin (α1-AT), needs to remain exposed in a metastable active conformation. The α1-AT RCL is sequestered in a β-sheet in the stable latent conformation. Thus, to be functional, α1-AT must always fold to a metastable conformation while avoiding folding to a stable conformation. We explore the structural basis of this choice using folding simulations of coarse-grained structure-based models of the two α1-AT conformations. Our simulations capture the key features of folding experiments performed on both conformations. The simulations also show that the free energy barrier to fold to the latent conformation is much larger than the barrier to fold to the active conformation. An entropically stabilized on-pathway intermediate lowers the barrier for folding to the active conformation. In this intermediate, the RCL is in an exposed configuration, and only one of the two α1-AT domains is folded. In contrast, early conversion of the RCL into a β-strand increases the coupling between the two α1-AT domains in the transition state and creates a larger barrier for folding to the latent conformation. Thus, unlike what happens in several proteins, where separate regions promote folding and function, the structure of the RCL, formed early during folding, determines both the conformational and the functional fate of α1-AT. Further, the short 12-residue RCL modulates the free energy barrier and the folding cooperativity of the large 370-residue α1-AT. Finally, we suggest experiments to test the predicted folding mechanism for the latent state.

}, issn = {1091-6490}, doi = {10.1073/pnas.1708173115}, author = {Giri Rao, V V Hemanth and Gosavi, Shachi} } @article {36269, title = {Foraging plasticity in obligate corallivorous Melon butterflyfish across three recently bleached reefs }, journal = {ETHOLOGY}, volume = {124 }, year = {2018}, month = {05/2018}, pages = {302-310 }, abstract = {

Because obligate corallivorous butterflyfish feed exclusively on coral polyps, they are particularly sensitive to changes in coral cover and its spatial distribution. To understand how such differences in coral cover influence obligate corallivores, we examined the densities and foraging behavior of Melon butterflyfish Chaetodon trifasciatus across three reefs in the Lakshadweep archipelago. These reefs suffered differential bleaching mortality after the 2010 El Ni{\~n}o Southern Oscillation, resulting in wide variation in coral cover and community composition. Despite these differences, C.\ trifasciatus were able to persist at similar densities across reefs. However, our analysis of high-resolution video recordings of multiple focal fish revealed that time budgets, bite rates, and diet selectivity differed significantly. Fish in resource-poor reefs spent more time moving between coral patches and less time foraging than ones in relatively resource-rich reefs. We also found that fish in resource-poor reefs had higher bite rates and were less selective in their foraging. Our results provide novel insights into how obligate corallivores cope with even large differences in resource availability. At a time when we are rapidly losing corals to repeated climate-induced bleaching events, this flexibility may represent a critical mechanism that enables persistence of obligate corallivores in resource-poor reefs, even if it does not guarantee longer-term survival.

}, doi = {10.1111/eth.12733 }, author = {Zambre, AM and Arthur, R} } @article {45438, title = {{\textquoteleft}Foresting{\textquoteright} the grassland: Historical management legacies in forest-grassland mosaics in southern India, and lessons for the conservation of tropical grassy biomes}, journal = {Biological Conservation}, volume = {224}, year = {2018}, month = {08/2018}, pages = {144-152}, abstract = {

Colonial encounters with tropical ecosystems were primarily driven by profit-oriented management practices; witness the extensive network of timber and forestry practices that were set up across colonial India. In contrast, the colonial engagement with the montane forest-grassland mosaics of the higher reaches of the Western Ghats in southern India was marked by intensive investment in vegetation management by colonial foresters that yielded no profits. In this archival study, we trace the history of extensive vegetation transformation in this landscape from the early nineteenth to the early twentieth century. We show how the misperception that the grasslands within this mosaic must have resulted from tree felling, fire-setting and buffalo grazing by indigenous communities led colonial foresters into a century-long effort at {\textquoteleft}foresting{\textquoteright} the grasslands, primarily through large-scale planting of exotic tree species. These efforts persisted despite economic losses and ecological evidence that native tree seedlings planted in the grasslands repeatedly failed to establish. These policies continued unabated into the late twentieth century in newly independent India. Today, the once picturesque landscapes of these ancient forest-grassland mosaics are diminished by large-scale plantations of exotic species. Some of these species have become invasive and pose significant threats to the remnant natural grasslands. While this historical narrative is set in the forest-grassland mosaics of southern India, it finds striking parallels in the current day, with grasslands and savannas globally threatened by the misperception that they are {\textquoteleft}degraded ecosystems{\textquoteright} that can be {\textquoteleft}forested{\textquoteright} or converted to other {\textquoteleft}productive{\textquoteright} land uses. We suggest that this case history portends the potential fates of many of earth{\textquoteright}s threatened tropical grasslands and savannas.

}, doi = {10.1016/j.biocon.2018.05.029}, author = {Joshi, Atul A and Mahesh Sankaran and Ratnam, Jayashree} } @article {45418, title = {Functional analysis of mammalian phospholipase D enzymes.}, journal = {Biosci Rep}, year = {2018}, month = {2018 Oct 28}, abstract = {

Phosphatidylcholine-specific phospholipase D (PLD) hydrolyzes the phosphodiester bond of the phosphatidylcholine to generate phosphatidic acid (PA) and regulates several sub-cellular functions. Mammalian genomes contain two genes encoding distinct isoforms of PLD in contrast to invertebrate genomes that include a single PLD gene. However, the significance of two genes within a genome encoding the same biochemical activity remains unclear. Recently, loss of function in the only PLD gene in was reported to result in reduced PA levels and a PA dependent collapse of the photoreceptor plasma membrane due to defects in vesicular transport. Phylogenetic analysis reveals that human PLD1 (hPLD1)is evolutionarily closer to dPLD than humanPLD2 (hPLD2). In this study we expressed hPLD1 and hPLD2 in and found that while reconstitution of hPLD1 is able to completely rescue retinal degeneration in a loss of function dPLD mutant,hPLD2 was less effective in its ability to mediate a rescue. Using a newly developed analytical method, we determined the acyl chain composition of PA species produced by each enzyme. While dPLD was able to restore the levels of most PA species in cells, hPLD1 and hPLD2\  each were unable to restore the levels of a subset of unique species of PA. Finally, we found that in contrast to hPLD2, dPLD and hPLD1 are uniquely distributed to the sub-plasma membrane region in photoreceptors. In summary hPLD1 likely represents the ancestral PLD in mammalian genomes while hPLD2 represents neofunctionalization to generate PA at distinct sub-cellular membranes.

}, issn = {1573-4935}, doi = {10.1042/BSR20181690}, author = {Panda, Aniruddha and Thakur, Rajan and Krishnan, Harini and Naik, Amruta and Shinde, Dhananjay and Raghu, Padinjat} } @article {30153, title = {GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving.}, journal = {Proc Natl Acad Sci U S A}, year = {2018}, month = {2018 Feb 13}, abstract = {

Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available into investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed an algorithm for automated analysis of leg motion to characterize the walking parameters of wild-type flies from high-speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walkingOur findings indicate that targeted down-regulation of the GABAreceptor Rdl (Resistance to Dieldrin) in leg motoneurons results in a dramatic reduction of walking speed and step length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together, these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving.

}, issn = {1091-6490}, doi = {10.1073/pnas.1713869115}, author = {Gowda, Swetha B M and Paranjpe, Pushkar D and Reddy, O Venkateswara and Thiagarajan, Devasena and Palliyil, Sudhir and Reichert, Heinrich and VijayRaghavan, K} } @article {48888, title = {Gene expression is implicated in the ability of pikas to occupy Himalayan elevational gradient.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0207936}, abstract = {

Species are shifting their ranges due to climate change, many moving to cooler and higher locations. However, with elevation increase comes oxygen decline, potentially limiting a species{\textquoteright} ability to track its environment depending on what mechanisms it has available to compensate for hypoxic stress. Pikas (Family Ochotonidae), cold-specialist small mammal species, are already undergoing elevational range shifts. We collected RNA samples from one population of Ochotona roylei in the western Himalaya at three sites- 3,600, 4,000, and 5,000 meters-and found no evidence of significant population genetic structure nor positive selection among sites. However, out of over 10,000 expressed transcripts, 26 were significantly upregulated at the 5,000 m site and were significantly enriched for pathways consistent with physiological compensation for limited oxygen. These results suggest that differences in gene expression may play a key role in enabling hypoxia tolerance on this local scale, indicating elevational flexibility that may facilitate successful range shifts in response to climate change.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0207936}, author = {Solari, Katherine A and Ramakrishnan, Uma and Hadly, Elizabeth A} } @article {24295, title = {Gene regulation and species-specific evolution of free-flight odor-tracking in Drosophila.}, journal = {Mol Biol Evol}, volume = {35}, year = {2018}, month = {01/2018}, pages = {3-15}, abstract = {

The flight ability of insects has coevolved with the development of organs necessary for takeoff from the ground, and to generate and modulate lift while flying in complex environments. Flight orientation to the appropriate food source and mating partner depends on the perception and integration of multiple chemical signals. We used a wind tunnel-based assay to investigate the natural and molecular evolution of free-flight odor-tracking behavior in Drosophila. First, the comparison of female and male flies of several populations and species revealed substantial sex-related, inter- and intra-specific variations for distinct flight features. In these flies, we compared the molecular structure of desat1, a fast-evolving gene involved in multiple aspects of pheromonal communication in Drosophila. We manipulated desat1 regulation and found that both neural and non-neural tissues influence distinct flight features. Together, our data suggest that desat1 is involved in the evolution of free-flight odor-tracking behaviors in Drosophila.

}, issn = {1537-1719}, doi = {10.1093/molbev/msx241}, author = {Houot, Benjamin and Cazal{\'e}-Debat, Laurie and Fraichard, St{\'e}phane and Everaerts, Claude and Saxena, Nitesh and Sane, Sanjay P and Ferveur, Jean-Fran{\c c}ois} } @article {38421, title = {Genome-wide survey of remote homologues for protein domain superfamilies of known structure reveals unequal distribution across structural classes.}, journal = {Mol Omics}, year = {2018}, month = {2018 Jul 04}, abstract = {

Domains are the basic building blocks of proteins which can combine to give rise to different domain architectures. Annotation of domains in a sequence is the first step towards understanding the biological function. Since there are a limited number of folds and evolutionarily related proteins have a similar structure, function can be inferred through remote homology. Computational sequence searches were performed for remote homologues on genomes of around \~{}160 000 different organisms, starting from nearly 11 000 superfamily queries of known structure. Case studies revealed that most of the associated domains are involved in the same biological process. Using all the proteins predicted to have at least one structural domain, a coverage of 61\% of Pfam families was achieved which is higher than the existing methods (43.36\% by SIFTS). Taxonomic analysis of the proteins revealed 493 superfamilies in all the major kingdoms of life and a few lateral gene transfers between viruses and cellular organisms. The distribution of remote homologues across different classes, folds and superfamilies was studied and reveals that sequences are unequally distributed across structural classes. Finally, domain architectures were computed for the homologues and these data were compiled for each superfamily and organism.

}, issn = {2515-4184}, doi = {10.1039/c8mo00008e}, author = {Iyer, Meenakshi S and Joshi, Adwait G and Sowdhamini, Ramanathan} } @article {39421, title = {Gut microflora may facilitate adaptation to anthropic habitat: A comparative study in .}, journal = {Ecol Evol}, volume = {8}, year = {2018}, month = {2018 Jul}, pages = {6463-6472}, abstract = {

Anthropophilic species ("commensal" species) that are completely dependent upon anthropic habitats experience different selective pressures particularly in terms of food than their noncommensal counterparts. Using a next-generation sequencing approach, we characterized and compared the gut microflora community of 53 commensal and 59 noncommensal captured in 10 locations in the Western Ghats, India. We observed that, while species identity was important in characterizing the microflora communities of the two hosts, environmental factors also had a significant effect. While there was significant geographic variation in the microflora of the noncommensal , there was no effect of geographic distance on gut microflora of the commensal . Interestingly, host genetic distance did not significantly influence the community in either hosts. Collectively, these results indicate that a shift in habitat is likely to result in a change in the gut microflora community and imply that the gut microflora is a complex trait, influenced by various parameters in different habitats.

}, issn = {2045-7758}, doi = {10.1002/ece3.4040}, author = {Varudkar, Amruta and Ramakrishnan, Uma} } @article {34071, title = {Heard but not seen: Comparing bat assemblages and study methods in a mosaic landscape in the Western Ghats of India.}, journal = {Ecol Evol}, volume = {8}, year = {2018}, month = {2018 Apr}, pages = {3883-3894}, abstract = {

We used capture (mist-netting) and acoustic methods to compare the species richness, abundance, and composition of a bat assemblage in different habitats in the Western Ghats of India. In the tropics, catching bats has been more commonly used as a survey method than acoustic recordings. In our study, acoustic methods based on recording echolocation calls detected greater bat activity and more species than mist-netting. However, some species were detected more frequently or exclusively by capture. Ideally, the two methods should be used together to compensate for the biases in each. Using combined capture and acoustic data, we found that protected forests, forest fragments, and shade coffee plantations hosted similar and diverse species assemblages, although some species were recorded more frequently in protected forests. Tea plantations contained very few species from the overall bat assemblage. In riparian habitats, a strip of forested habitat on the river bank improved the habitat for bats compared to rivers with tea planted up to each bank. Our results show that shade coffee plantations are better bat habitat than tea plantations in biodiversity hotspots. However, if tea is to be the dominant land use, forest fragments and riparian corridors can improve the landscape considerably for bats. We encourage coffee growers to retain traditional plantations with mature native trees, rather than reverting to sun grown coffee or coffee shaded by a few species of timber trees.

}, issn = {2045-7758}, doi = {10.1002/ece3.3942}, author = {Wordley, Claire F R and Sankaran, Mahesh and Mudappa, Divya and Altringham, John D} } @article {32473, title = {Hippocampal and amygdalar cell-specific translation is similar soon after stress but diverge over time.}, journal = {Hippocampus}, year = {2018}, month = {2018 Apr 07}, abstract = {

Stress is known to cause contrasting patterns of morphological and physiological plasticity in the hippocampus and amygdala. An obligatory cellular process underlying such neural changes is de novo translation and alterations in protein expression. Yet the nature of the translational response to stress in neurons remains largely unexplored. Even less is known about how glia are affected. Using a click-chemistry-based method to label the de novo proteome in live brain slices, we monitored translation in neurons and astrocytes of the basolateral amygdala (BLA) and dorsal hippocampal area CA3 (dCA3) in rats at different time-points after a single 2-hour exposure to immobilization stress. We observed enhancements in neuronal translation in both brain regions 1 hour after stress. This initial increase persisted in the BLA up to 10 days afterwards. In contrast, dCA3 neuronal translation gradually decreased to below control levels 10 days later. Translation profiles of dCA3 astrocytes followed timelines similar to neurons, but in BLA astrocytes translation peaked 1day later and remained elevated 10 days later. Together our results demonstrate that stress causes an immediate upregulation of protein synthesis in both amygdalar and hippocampal neurons and astrocytes. However, these two areas eventually exhibit opposite temporal profiles of protein expression well after the end of stress. These findings identify new metrics of stress-induced plasticity at the level of cell-type specific proteomic landscape that may provide important insights into the molecular basis of the divergent temporal effects of stress across brain regions and biological scales. This article is protected by copyright. All rights reserved.

}, issn = {1098-1063}, doi = {10.1002/hipo.22845}, author = {Madan, Jesvin S and Gupta, Kanika and Chattarji, Sumantra and Bhattacharya, Aditi} } @article {28567, title = {Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway.}, journal = {Insect Mol Biol}, volume = {27}, year = {2018}, month = {2018 Feb}, pages = {90-98}, abstract = {

In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr-1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses.

}, issn = {1365-2583}, doi = {10.1111/imb.12350}, author = {Singh, A S and Shah, A and Brockmann, A} } @article {30982, title = {Identification of a Single Pair of Interneurons for Bitter Taste Processing in the Drosophila Brain.}, journal = {Curr Biol}, year = {2018}, month = {2018 Feb 21}, abstract = {

Drosophila has become an excellent model system for investigating the organization and function of the gustatory system due to the relatively simple neuroanatomical organization of its brain and the availability of powerful genetic and transgenic technology. Thus, at the molecular and cellular levels, a great deal of insight into the peripheral detection and coding of gustatory information has already been attained. In contrast, much less is known about the central neural circuits that process this information and induce behaviorally appropriate motor output. Here, we combine functional behavioral tests with targeted transgene expression through specific driver lines to identify a single bilaterally homologous pair of bitter-sensitive interneurons that are located in the subesophageal zone of the brain. Anatomical and functional data indicate that these interneurons receive specific synaptic input from bitter-sensitive gustatory receptor neurons. Targeted transgenic activation and inactivation experiments show that these bitter-sensitive interneurons can largely suppress the proboscis extension reflex to appetitive stimuli, such as sugar and water. These functional experiments, together with calcium-imaging studies and calcium-modulated photoactivatable ratiometric integrator (CaMPARI) labeling, indicate that these first-order local interneurons play an important role in the inhibition of the proboscis extension reflex that occurs in response to bitter tastants. Taken together, our studies present a cellular identification and functional characterization of a key gustatory interneuron in the bitter-sensitive gustatory circuitry of the adult fly.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2018.01.084}, author = {Bohra, Ali Asgar and Kallman, Benjamin R and Reichert, Heinrich and VijayRaghavan, K} } @article {45439, title = {Identification of splice variant of in ssp. genotypes under salinity stress.}, journal = {3 Biotech}, volume = {8}, year = {2018}, month = {2018 Aug}, pages = {345}, abstract = {

G-box-binding factors are plant transcription factors, involved in a wide range of biological processes including abiotic stress responses. In this study, we analyzed the expression of during salt stress in two contrasting spp. genotypes, and . Two-day-old seedlings were exposed to NaCl stress under two different conditions. One set was exposed to 100\ mM NaCl before transferring to 250\ mM (induction stress), while another set was transferred directly to 250\ mM (shock stress). During early induction stress, was up-regulated in when compared to . We cloned full-length from these two genotypes, and analyzed the sequences. Our analysis indicated the presence of transcript variants, which are designated as and variant retained introns, which lead to the generation of premature termination codon. transcript levels were not significantly different at 12-h of induction stress in and . At 24-h of shock stress, was up-regulated in both genotypes and the transcript was more in . Since, and are predicted to be splice variants, we examined expression pattern of , a splicing factor and component of the spliceosome. In induction stress, was up-regulated at 12- and 24-h in when compared to . On the contrary, at 24-h shock stress, was down-regulated in when compared to . It is possible that expression was increased in during induction stress for accurate splicing that could aid in tolerance. This is the first report on splice variant and the variant could have specific functions linked to stress tolerance in rice.

}, issn = {2190-572X}, doi = {10.1007/s13205-018-1370-4}, author = {Ashwini, Narasimha and Sajeevan, Radha Sivarajan and Udayakumar, Makarala and Nataraja, Karaba N} } @article {32021, title = {Identification, purification, biochemical and mass spectrometric characterization of novel phycobiliproteins from a marine red alga, Centroceras clavulatum.}, journal = {Int J Biol Macromol}, year = {2018}, month = {2018 Mar 26}, abstract = {

Phycobilisomes are light-harvesting protein complexes and are widely distributed in red algae and cyanobacteria. Each phycobilisome contains highly fluorescent protein components called phycobiliproteins. Based upon the distinct physiochemical properties, phycobiliproteins are classified as allophycocyanin, phycocyanin, phycoerythrin and phycoerythrocyanin. In the present study, we describe purification and structural characterization of a novel phycocyanin and phycoerythrin isolated from a marine red macroalga, Centroceras clavulatum. The absorbance and fluorescence studies indicated that the purified proteins belong to R-Phycocyanin (R-PC) and R-Phycoerythrin (R-PE). The single bands under native-polyacrylamide gel electrophoresis revealed the intact molecular weights of R-PC and R-PE as 110 kDa and 250 kDa. The polypeptide compositions of the two proteins were demonstrated by SDS-PAGE. The result showed that R-PC contains two bands at 17 and 21 kDa and were identified as α and β subunits through mass spectrometry based proteomics experiments. SDS-PAGE of R-PE showed three distinct bands at 18, 19 and 35 kDa and was subsequently identified as α, β and γ subunits. The near-complete amino acid sequences of α and β subunits of R-PC and R-PE were derived from mass spectrometric data combined with Mascot software and multiple de novo sequencing tools followed by homology search and manual validation.

}, issn = {1879-0003}, doi = {10.1016/j.ijbiomac.2018.03.153}, author = {Nair, Divya and Krishna, Jissa Gopala and Panikkar, Mamkoottathil Velayudhan Nataraja and Nair, Bipin Gopalakrishnan and Pai, Jayashree Gopalakrishna and Nair, Sudarslal Sadasivan} } @article {51227, title = {Identifying the Cellular Correlates of Antipsychotic Drugs.}, journal = {eNeuro}, volume = {5}, year = {2018}, month = {2018 Sep-Oct}, abstract = {

GPCRs such as 5-HT and D2 are implicated in the therapeutic and the side effects of antipsychotics. However, the pattern of brain activity that leads to the behavioral effects of antipsychotics is poorly understood. To address this question, we used the transgenic {\textquoteright}FosTRAP{\textquoteright} mice (), where a fluorescent reporter marks the cells responsive to the stimulus of interest. Here, the stimulus was an administration of various antipsychotic drugs. In case of typical antipsychotics such as Haloperidol, the active cells were predominantly found in the striatum, whereas in case of the atypical antipsychotics (Clozapine and Olanzapine), -induced cells were more numerous in the cortical regions, e.g., orbital cortex, piriform cortex. Curiously, we also observed ependymal cells to be a novel cellular target of atypical antipsychotics. 5-HT is considered to be a major target for atypical antipsychotics. Therefore, we bred {\textquoteright}FosTRAP{\textquoteright} mice with 5-HT knock-out (KO) mice and tested their response to the prototype of atypical antipsychotics, Clozapine. Interestingly, the absence of 5-HT did not significantly affect the number of -induced cells in the cortical regions. However, the ependymal cells showed a dramatically reduced response to Clozapine in the absence of 5-HT. In summary, the TRAP system has allowed us to identify various region-specific activity induced by antipsychotics and novel cellular targets of the antipsychotics. These results serve as a "proof of principle" study that can be extended to explore the biochemical and physiological changes brought about by antipsychotics and specifically identify antipsychotic-responsive cells in the live tissue.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0220-18.2018}, author = {Joshi, Radhika S and Panicker, Mitradas M} } @article {45432, title = {"In a tree by the brook, there{\textquoteright}s a songbird who sings": Woodlands in an agricultural matrix maintain functionality of a wintering bird community.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0201657}, abstract = {

The agricultural matrix has increasingly been recognized for its potential to supplement Protected Areas (PAs) in biodiversity conservation. This potential is highly contextual, depending on composition and spatial configuration of matrix elements and their mechanistic relationship with biological communities. We investigate the effects of local vegetation structure, and proximity to a PA on the site-use of different guilds in a wintering bird community within the PA, and in wooded land-use types in the surrounding matrix. We used occupancy models to estimate covariate-guild relationships and predict site-use. We also compared species richness (estimated through capture-recapture models) and species na{\"\i}ve site-use between the PA and the matrix to evaluate taxonomic changes. We found that tree cover did not limit the site-use of most guilds of the community, probably due to high canopy cover across all chosen sites. Exceptions to this were guilds comprising generalist species. Shrub cover and bamboo cover had important effects on some woodland-associated guilds, suggesting a change in limiting factors for site-use under adequate tree cover. Site-use across the matrix was high for all analyzed guilds. This was found to be due to three non-exclusive reasons: (i) presence of one or more ubiquitous species (found all across the landscape) within some guilds, (ii) redundancy of species within guilds that buffered against a decrease in site-use, and (iii) turnover in guild composition/abundances to more generalist species from PA to matrix. Estimated species richness was higher in the matrix (107{\textpm} 11; mean {\textpm} SE) than in the PA (90{\textpm} 7), which may have been in part due to the addition of generalist species in the matrix. Understanding factors that limit biological communities is crucial to better managing the ever-increasing matrix for biodiversity conservation. Our study provides insights into the effects of different components of vegetation structure on the bird community in wooded land-use types in the matrix. We highlight the value of woodlands surrounding PAs in maintaining multiple guilds, and hence, the functionality of a wintering bird community. However, we caution that the matrix may fall short in retaining some specialized species of the community.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0201657}, author = {Syiem, Biang La Nam and Goswami, Varun R and Vasudev, Divya} } @article {30081, title = {Indian Ocean humpback dolphin (Sousa plumbea) estuary-use patterns in Kochi harbor, India}, journal = {MARINE MAMMAL SCIENCE}, volume = {34}, year = {2018}, month = {01/2018}, pages = {208-219}, doi = {10.1111/mms.12438}, author = {Panicker, Divya and Haris, Asad and Sutaria, Dipani} } @article {25690, title = {Indomethacin elicits proteasomal dysfunctions develops apoptosis through mitochondrial abnormalities.}, journal = {J Cell Physiol}, volume = {233}, year = {2018}, month = {2018 Feb}, pages = {1685-1699}, abstract = {

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that are mainly used to treat pain, inflammation, and fever via cyclooxygenase-2 (COX-2) inhibition. There are abundant findings that uncover the hidden critical chemotherapeutics potential of NSAIDs in cancer treatment. However, still the precise mechanism by which NSAIDs could be used as an effective anti-tumor agent in the prevention of carcinogenesis is not well understood. Here, we show that indomethacin, a well-known NSAID, induces proteasomal dysfunction that results in accumulation of unwanted proteins, mitochondrial abnormalities, and successively stimulate apoptosis in cells. We observed the interaction of indomethacin with proteasome and noticed the massive accumulation of intracellular ubiquitin-positive proteins, which might be due to the suppression of proteasome activities. Furthermore, we also found that exposure of indomethacin causes the accumulation of critical proteasomal substrates that consequently generate severe mitochondrial abnormalities and prompt up key apoptotic events in cells. Our results demonstrate how indomethacin affects normal proteasomal functions and induces mitochondrial apoptosis in cells. These findings also improve our current understanding of how NSAIDs can exhibit crucial anti-proliferative effects in cells. In near future, our findings may suggest a new possible strategy for the development of specific proteasome inhibitors in conjunction with other chemo-preventive anticancer agents.

}, issn = {1097-4652}, doi = {10.1002/jcp.26081}, author = {Amanullah, Ayeman and Mishra, Ribhav and Upadhyay, Arun and Reddy, Pothula P and Das, Ranabir and Mishra, Amit} } @article {45929, title = {Infectivity of adeno-associated virus serotypes in mouse testis.}, journal = {BMC Biotechnol}, volume = {18}, year = {2018}, month = {2018 Nov 01}, pages = {70}, abstract = {

BACKGROUND: Recombinant adeno-associated viruses (AAVs) are emerging as favoured transgene delivery vectors for both research applications and gene therapy. In this context, a thorough investigation of the potential of various AAV serotypes to transduce specific cell types is valuable. Here, we rigorously tested the infectivity of a number of AAV serotypes in murine testis by direct testicular injection.

RESULTS: We report the tropism of serotypes AAV2, 5, 8, 9 and AAVrh10 in mouse testis. We reveal unique infectivity of AAV2 and AAV9, which preferentially target intertubular testosterone-producing Leydig cells. Remarkably, AAV2 TM, a mutant for capsid designed to increase transduction, displayed a dramatic alteration in tropism; it infiltrated seminiferous tubules unlike wildtype AAV2 and transduced Sertoli cells. However, none of the AAVs tested infected spermatogonial cells.

CONCLUSIONS: In spite of direct testicular injection, none of the tested AAVs appeared to infect sperm progenitors as assayed by reporter expression. This lends support to the current view that AAVs are safe gene-therapy vehicles. However, testing the presence of rAAV genomic DNA in germ cells is necessary to assess the risk of individual serotypes.

}, issn = {1472-6750}, doi = {10.1186/s12896-018-0479-1}, author = {Rajasekaran, Santhanasabapathy and Thatte, Jayashree and Periasamy, Jayaprakash and Javali, Alok and Jayaram, Manjunath and Sen, Dwaipayan and Krishnagopal, Akshaya and Jayandharan, Giridhara R and Sambasivan, Ramkumar} } @article {45300, title = {Influence of midgut microbiota in Anopheles stephensi on Plasmodium berghei infections.}, journal = {Malar J}, volume = {17}, year = {2018}, month = {2018 Oct 25}, pages = {385}, abstract = {

BACKGROUND: The native gut microbiota of Anopheles mosquitoes is known to play a key role in the physiological function of its host. Interestingly, this microbiota can also influence the development of Plasmodium in its host mosquitoes. In recent years, much interest has been shown in the employment of gut symbionts derived from vectors in the control of vector-borne disease transmission. In this study, the midgut microbial diversity has been characterized among laboratory-reared adult Anopheles stephensi mosquitoes, from the colony created by rearing progeny of wild-caught mosquitoes (obtained from three different locations in southern India) for multiple generations, using 16S ribosomal RNA (rRNA) gene sequencing approach. Further, the influence of native midgut microbiota of mosquitoes on the development of rodent malaria parasite Plasmodium berghei in its host has been studied.

METHODS: The microbial diversity associated with the midgut of An. stephensi mosquitoes was studied by sequencing V3 region of 16S ribosomal RNA (rRNA) gene. The influence of native midgut microbiota of An. stephensi mosquitoes on the susceptibility of the mosquitoes to rodent malaria parasite P. berghei was studied by comparing the intensity and prevalence of P. berghei infection among the antibiotic treated and untreated cohorts of mosquitoes.

RESULTS: The analysis of bacterial diversity from the midguts of An. stephensi showed Proteobacteria as the most dominant population among the three laboratory-reared strains of An. stephensi studied. Major genera identified among these mosquito strains were Acinetobacter, Pseudomonas, Prevotella, Corynebacterium, Veillonella, and Bacillus. The mosquito infectivity studies carried out to determine the implication of total midgut microbiota on P. berghei infection showed that mosquitoes whose native microbiota cleared with antibiotics had increased susceptibility to P. berghei infection compared to the antibiotic untreated mosquitoes with its natural native microbiota.

CONCLUSIONS: The use of microbial symbiont to reduce the competence of vectors involved in disease transmission has gained much importance in recent years as an emerging alternative approach towards disease control. In this context, the present study was aimed to identify the midgut microbiota composition of An. stephensi, and its effect on the development of P. berghei. Interestingly, the analysis of midgut microbiota from An. stephensi revealed the presence of genus Veillonella in Anopheles species for the first time. Importantly, the study also revealed the negative influence of total midgut microbiota on the development of P. berghei in three laboratory strains of An. stephensi, emphasizing the importance of understanding the gut microbiota in malaria vectors, and its relationship with parasite development in designing strategies to control malaria transmission.

}, issn = {1475-2875}, doi = {10.1186/s12936-018-2535-7}, author = {Kalappa, Devaiah Monnanda and Subramani, Pradeep Annamalai and Basavanna, Sowmya Kanchanahalli and Ghosh, Susanta Kumar and Sundaramurthy, Varadharajan and Uragayala, Sreehari and Tiwari, Satyanarayan and Anvikar, Anupkumar R and Valecha, Neena} } @article {36106, title = {Interactions Between Epidermal Keratinocytes, Dendritic Epidermal T-Cells, and Hair Follicle Stem Cells.}, journal = {Methods Mol Biol}, year = {2018}, month = {2018 Jun 13}, abstract = {

The interplay of immune cells and stem cells in maintaining skin homeostasis and repair is an exciting new frontier in cutaneous biology. With the growing appreciation of the importance of this new crosstalk comes the requirement of methods to interrogate the molecular underpinnings of these leukocyte-stem cell interactions. Here we describe how a combination of FACS, cellular coculture assays, and conditioned media treatments can be utilized to advance our understanding of this emerging area of intercellular communication between immune cells and stem cells.

}, issn = {1940-6029}, doi = {10.1007/7651_2018_155}, author = {Badarinath, Krithika and Dutta, Abhik and Hegde, Akshay and Pincha, Neha and Gund, Rupali and Jamora, Colin} } @article {43855, title = {The interplay between electrical and chemical synaptogenesis.}, journal = {J Neurophysiol}, year = {2018}, month = {2018 Aug 01}, abstract = {

Neurons communicate with each other via electrical or chemical synaptic connections. The pattern and strength of connections between neurons is critical for generating appropriate output. What mechanisms govern the formation of electrical and/or chemical synapses between two neurons? Recent studies indicate that common molecular players could regulate the formation of both these classes of synapses. In addition, electrical and chemical synapses can mutually co-regulate each other{\textquoteright}s formation. Electrical activity, generated spontaneously by the nervous system, or initiated from sensory experience, plays an important role in this process, leading to the selection of appropriate connections and the elimination of inappropriate ones. In this review, we discuss recent studies that shed light on the formation and developmental interactions of chemical and electrical synapses.

}, issn = {1522-1598}, doi = {10.1152/jn.00398.2018}, author = {Jabeen, Shaista and Thirumalai, Vatsala} } @article {45310, title = {The Interplay of Host Autophagy and Eukaryotic Pathogens.}, journal = {Front Cell Dev Biol}, volume = {6}, year = {2018}, month = {2018}, pages = {118}, abstract = {

For intracellular pathogens, host cells provide a replicative niche, but are also armed with innate defense mechanisms to combat the intruder. Co-evolution of host and pathogens has produced a complex interplay of host-pathogen interactions during infection, with autophagy emerging as a key player in the recent years. Host autophagy as a degradative process is a significant hindrance to intracellular growth of the pathogens, but also can be subverted by the pathogens to provide support such as nutrients. While the role of host cell autophagy in the pathogenesis mechanisms of several bacterial and viral pathogens have been extensively studied, less is known for eukaryotic pathogens. In this review, we focus on the interplay of host autophagy with the eukaryotic pathogens and the fungal pathogens and . The differences between these eukaryotic pathogens in terms of the host cell types they infect, infective strategies and the host responses required to defend against them provide an interesting insight into how they respond to and interact with host cell autophagy. Due to the ability to infect multiple host species and cell types during the course of their usually complex lifestyles, autophagy plays divergent roles even for the same pathogen. The scenario is further compounded since many of the eukaryotic pathogens have their own sets of either complete or partial autophagy machinery. Eukaryotic pathogen-autophagy interplay is thus a complex relationship with many novel insights for the basic understanding of autophagy, and potential for clinical relevance.

}, issn = {2296-634X}, doi = {10.3389/fcell.2018.00118}, author = {Evans, Robert J and Sundaramurthy, Varadharajan and Frickel, Eva-Maria} } @article {29626, title = {Intrinsic Disorder in a Well-Folded Globular Protein.}, journal = {J Phys Chem B}, year = {2018}, month = {2018 Feb 01}, abstract = {

The folded structure of the heterodimeric sweet protein monellin mimics single-chain proteins with topology β1-α1-β2-β3-β4-β5 (chain A: β3-β4-β5; chain B: β1-α1-β2). Furthermore, like naturally occurring single-chain proteins of a similar size, monellin folds cooperatively with no detectable intermediates. However, the two monellin chains, A and B, are marginally structured in isolation and fold only upon binding to each other. Thus, monellin presents a unique opportunity to understand the design of intrinsically disordered proteins that fold upon binding. Here, we study the folding of a single-chain variant of monellin (scMn) using simulations of an all heavy-atom structure-based model. These simulations can explain mechanistic details derived from scMn experiments performed using several different structural probes. scMn folds cooperatively in our structure-based simulations, as is also seen in experiments. We find that structure formation near the transition-state ensemble of scMn is not uniformly distributed but is localized to a hairpin-like structure which contains one strand from each chain (β2, β3). Thus, the sequence and the underlying energetics of heterodimeric monellin promote the early formation of the interchain interface (β2-β3). By studying computational scMn mutants whose "interchain" interactions are deleted, we infer that this energy distribution allows the two protein chains to remain largely disordered when this interface is not folded. From these results, we suggest that cutting the protein backbone of a globular protein between residues which lie within its folding nucleus may be one way to construct two disordered fragments which fold upon binding.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b12546}, author = {Mascarenhas, Nahren Manuel and Terse, Vishram L and Gosavi, Shachi} } @article {29621, title = {Investigating the effect of key mutations on the conformational dynamics of Toll-like receptor dimers through molecular dynamics simulations and protein structure networks.}, journal = {Proteins}, year = {2018}, month = {2018 Jan 31}, abstract = {

The Toll-like receptors (TLRs) are critical components of the innate immune system due to their ability to detect conserved pathogen-associated molecular patterns, present in bacteria, viruses and other microorganisms. Ligand detection by TLRs leads to a signalling cascade, mediated by interactions among TIR domains present in the receptors, the bridging adaptors as well as sorting adaptors. The BB loop is a highly conserved region present in the TIR domain and is crucial for mediating interactions among TIR domain-containing proteins. Mutations in the BB loop of the Toll-like receptors, such as the A795P mutation in TLR3 and the P712H mutation (Lpsd mutation) in TLR4, have been reported to disrupt or alter downstream signalling. While the phenotypic effect of these mutations is known, the underlying effect of these mutations on the structure, dynamics and interactions with other TIR domain-containing proteins is not well understood. Here, we have attempted to investigate the effect of the BB loop mutations on the dimer form of TLRs, using TLR2 and TLR3 as case studies. Our results based on molecular dynamics simulations, protein-protein interaction analyses and protein structure network analyses highlight significant differences between the dimer interfaces of the wild-type and mutant forms and provide a logical reasoning for the effect of these mutations on adaptor binding to TLRs. Furthermore, it also leads us to propose a hypothesis for the differential requirement of signalling and bridging adaptors by TLRs. This could aid in further understanding of the mechanisms governing such signalling pathways. This article is protected by copyright. All rights reserved.

}, issn = {1097-0134}, doi = {10.1002/prot.25467}, author = {Mahita, Jarjapu and Sowdhamini, Ramanathan} } @article {35862, title = {Investigating the viral ecology of global bee communities with high-throughput metagenomics.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 Jun 11}, pages = {8879}, abstract = {

Bee viral ecology is a fascinating emerging area of research: viruses exert a range of effects on their hosts, exacerbate impacts of other environmental stressors, and, importantly, are readily shared across multiple bee species in a community. However, our understanding of bee viral communities is limited, as it is primarily derived from studies of North American and European Apis mellifera populations. Here, we examined viruses in populations of A. mellifera and 11 other bee species from 9 countries, across 4 continents and Oceania. We developed a novel pipeline to rapidly and inexpensively screen for bee viruses. This pipeline includes purification of encapsulated RNA/DNA viruses, sequence-independent amplification, high throughput sequencing, integrated assembly of contigs, and filtering to identify contigs specifically corresponding to viral sequences. We identified sequences for (+)ssRNA, (-)ssRNA, dsRNA, and ssDNA viruses. Overall, we found 127 contigs corresponding to novel viruses (i.e. previously not observed in bees), with 27 represented by \>0.1\% of the reads in a given sample, and 7 contained an RdRp or replicase sequence which could be used for robust phylogenetic analysis. This study provides a sequence-independent pipeline for viral metagenomics analysis, and greatly expands our understanding of the diversity of viruses found in bee communities.

}, issn = {2045-2322}, doi = {10.1038/s41598-018-27164-z}, author = {Galbraith, David A and Fuller, Zachary L and Ray, Allyson M and Brockmann, Axel and Frazier, Maryann and Gikungu, Mary W and Martinez, J Francisco Iturralde and Kapheim, Karen M and Kerby, Jeffrey T and Kocher, Sarah D and Losyev, Oleksiy and Muli, Elliud and Patch, Harland M and Rosa, Cristina and Sakamoto, Joyce M and Stanley, Scott and Vaudo, Anthony D and Grozinger, Christina M} } @article {36270, title = {Living with dolphins: Local ecological knowledge and perceptions of small cetaceans along the Sindhudurg coastline of Maharashtra, India}, journal = {MARINE MAMMAL SCIENCE }, volume = {34 }, year = {2018}, month = {04/2018}, pages = {488-498}, doi = {10.1111/mms.12466 }, author = {Jog, K and Sule, M and Bopardikar, I and Patankar, V and Sutaria, D} } @article {27277, title = {Local loss and spatial homogenization of plant diversity reduce ecosystem multifunctionality.}, journal = {Nat Ecol Evol}, volume = {2}, year = {2018}, month = {2017 Dec 04}, pages = {50-56}, abstract = {

Biodiversity is declining in many local communities while also becoming increasingly homogenized across space. Experiments show that local plant species loss reduces ecosystem functioning and services, but the role of spatial homogenization of community composition and the potential interaction between diversity at different scales in maintaining ecosystem functioning remains unclear, especially when many functions are considered (ecosystem multifunctionality). We present an analysis of eight ecosystem functions measured in 65 grasslands worldwide. We find that more diverse grasslands-those with both species-rich local communities (α-diversity) and large compositional differences among localities (β-diversity)-had higher levels of multifunctionality. Moreover, α- and β-diversity synergistically affected multifunctionality, with higher levels of diversity at one scale amplifying the contribution to ecological functions at the other scale. The identity of species influencing ecosystem functioning differed among functions and across local communities, explaining why more diverse grasslands maintained greater functionality when more functions and localities were considered. These results were robust to variation in environmental drivers. Our findings reveal that plant diversity, at both local and landscape scales, contributes to the maintenance of multiple ecosystem services provided by grasslands. Preserving ecosystem functioning therefore requires conservation of biodiversity both within and among ecological communities.

}, issn = {2397-334X}, doi = {10.1038/s41559-017-0395-0}, author = {Hautier, Yann and Isbell, Forest and Borer, Elizabeth T and Seabloom, Eric W and Harpole, W Stanley and Lind, Eric M and MacDougall, Andrew S and Stevens, Carly J and Adler, Peter B and Alberti, Juan and Bakker, Jonathan D and Brudvig, Lars A and Buckley, Yvonne M and Cadotte, Marc and Caldeira, Maria C and Chaneton, Enrique J and Chu, Chengjin and Daleo, Pedro and Dickman, Christopher R and Dwyer, John M and Eskelinen, Anu and Fay, Philip A and Firn, Jennifer and Hagenah, Nicole and Hillebrand, Helmut and Iribarne, Oscar and Kirkman, Kevin P and Knops, Johannes M H and La Pierre, Kimberly J and McCulley, Rebecca L and Morgan, John W and P{\"a}rtel, Meelis and Pascual, Jesus and Price, Jodi N and Prober, Suzanne M and Risch, Anita C and Sankaran, Mahesh and Schuetz, Martin and Standish, Rachel J and Virtanen, Risto and Wardle, Glenda M and Yahdjian, Laura and Hector, Andy} } @article {36661, title = {Maintaining tiger connectivity and minimizing extinction into the next century: Insights from landscape genetics and spatially-explicit simulations }, journal = {BIOLOGICAL CONSERVATION }, volume = {218}, year = {2018}, month = {02/2018}, pages = {181-191 }, doi = {10.1016/j.biocon.2017.12.022 }, author = {Thatte, Prachi and Joshi, A and Vaidyanathan, S and Landguth, E and Ramakrishnan, Uma} } @article {45303, title = {Major domestication-related phenotypes in indica rice are due to loss of miRNA-mediated laccase silencing.}, journal = {Plant Cell}, year = {2018}, month = {2018 Oct 19}, abstract = {

Domestication of rice included conversion of perennial wild species with few seeds to short plants that produced abundant seeds. Most domestication-associated changes were due to variations in transcription factors and other key genes such as enzymes. Here, we show that multiple yield-related traits associated with indica rice domestication are linked to micro (mi) RNA mediated regulation. Analysis of small (s) RNA datasets from cultivated indica rice lines, a few landraces and two wild relatives of rice revealed the presence of abundant 22-nucleotide (nt) reads in wild relatives that mapped to miR397 precursors. miR397 expressed at very high levels in wild relatives and at negligible levels in high-yielding cultivated lines. In its genera-specific form of 22-nt, miR397 targeted mRNAs coding for laccases to decay and induce robust secondary cascade silencing in wild species that required RNA-dependent RNA polymerase 6. In wild species of rice, reduced expression of laccases resulted in low lignification. As expected, over-expression of miR397 induced de-domestication phenotypes. Interestingly, nearly 26 unknown QTLs previously implicated for rice yield overlapped with laccases and miR397 genes. These results suggest the involvement of miRNAs in rice domestication-associated phenotypes.

}, issn = {1532-298X}, doi = {10.1105/tpc.18.00472}, author = {Swetha, Chenna and Basu, Debjani and Pachamuthu, Kannan and Tirumalai, Varsha and Nair, Ashwin and Prasad, Melvin and Shivaprasad, Padubidri V} } @article {45452, title = {Mass spectrometric identification of bromotryptophan containing conotoxin sequences from the venom of C.~amadis.}, journal = {Toxicon}, volume = {144}, year = {2018}, month = {2018 Mar 15}, pages = {68-74}, abstract = {

Four 30 residue conotoxin have been identified from the venom of C.\ amadis. MS/MS analysis of crude venom subjected to global reduction/alkylation yielded fragmentation patterns, which permitted searching and matching with a database of putative mature toxin sequences obtained from transcriptomic analysis. Of the four sequences identified, Am3408(Am6.1b), Am3452(Am6.1c), Am3136(Am6.2a) and Am3214(Am6.2b), three contain bromotryptophan residues, while an additional post translational modification, gamma carboxylation of glutamic acid, is present in Am3408(Am6.1b)/3452(Am6.1c). The conotoxins belong to the O1/O2 gene superfamily and possess cysteine framework VI/VII. While, the cysteine patterns show a similarity to omega conotoxins, the three C.\ amadis peptides are highly negatively charged and possess a significant content of hydrophobic residues.

}, issn = {1879-3150}, doi = {10.1016/j.toxicon.2018.02.005}, author = {Vijayasarathy, M and Balaram, P} } @article {31557, title = {Maximal Fluctuations of Confined Actomyosin Gels: Dynamics of the Cell Nucleus.}, journal = {Phys Rev Lett}, volume = {120}, year = {2018}, month = {2018 Mar 02}, pages = {098001}, abstract = {

We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in nonequilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply this generic result to the dynamics of deformations of the cell nucleus, and we demonstrate the appearance of a fluctuation maximum at a critical level of activity, in agreement with recent experiments [E. Makhija, D. S. Jokhun, and G. V. Shivashankar, Proc. Natl. Acad. Sci. U.S.A. 113, E32 (2016)PNASA60027-842410.1073/pnas.1513189113].

}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.120.098001}, author = {Rupprecht, J-F and Singh Vishen, A and Shivashankar, G V and Rao, M and Prost, J} } @article {31050, title = {Mechanism of aggregation and membrane interactions of mammalian prion protein.}, journal = {Biochim Biophys Acta}, year = {2018}, month = {2018 Mar 04}, abstract = {

The cellular prion protein (PrP), which is present ubiquitously in all mammalian neurons, is normally found to be linked to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. The conformational conversion of PrPinto misfolded and aggregated forms is associated with transmissible neurodegenerative diseases known as prion diseases. The importance of different misfolded conformations in prion diseases, and the mechanism by which prion aggregates induce neurotoxicity remain poorly understood. Multiple studies have been shown that the toxicity of misfolded prion protein is directly correlated with its ability to interact with and perturb membranes. This review describes the current progress toward understanding prion protein misfolding and aggregation, as well as the interaction of prion protein aggregates with lipid membrane.

}, issn = {0006-3002}, doi = {10.1016/j.bbamem.2018.02.031}, author = {Sabareesan, Ambadi Thody and Mathew, M K and Udgaonkar, Jayant B} } @article {43838, title = {Mechanistic and Structural Origins of the Asymmetric Barrier to Prion-like Cross-Seeding between Tau-3R and Tau-4R.}, journal = {J Mol Biol}, year = {2018}, month = {2018 Sep 26}, abstract = {

The spread and deposition of infectious fibrillar protein aggregates in the brain via a prion-like mechanism, is a critical component in the patho-physiology of various neurodegenerative diseases, including the tauopathies. In tauopathies, two isoforms of tau, containing three and four microtubule binding repeats (MTBRs), are found to aggregate, and the type of isoform present in aggregates, determines the type of tauopathy. Cross-seeding between the two tau isoforms is limited by an asymmetric barrier, similar to the species barrier that restricts prion transmission across species, whose origin has remained unclear. In this study, the growth of the tau fibrils is shown to be describable by a two-step Michaelis-Menten-like model. Delineation of the mechanism as a Michaelis-Menten-like mechanism has enabled a quantitative understanding of the asymmetric seeding barrier that exists between two isoforms of tau, tau-K18 and tau-K19 (which differ in containing four and three MTBRs, respectively), wherein tau-K18 fibrils cannot seed tau-K19 monomer. Furthermore, high-resolution structural analysis of the two isoforms shows that the structural core is more ordered in tau-K19 than in tau-K18. Hence, the current work provides kinetic and structural rationales for asymmetric seeding barriers in general, and for the two tau isoforms in particular.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2018.09.010}, author = {Kumar, Harish and Udgaonkar, Jayant B} } @article {45305, title = {Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 Oct 11}, pages = {4217}, abstract = {

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-06738-5}, author = {Thottacherry, Joseph Jose and Kosmalska, Anita Joanna and Kumar, Amit and Vishen, Amit Singh and Elosegui-Artola, Alberto and Pradhan, Susav and Sharma, Sumit and Singh, Parvinder P and Guadamillas, Marta C and Chaudhary, Natasha and Vishwakarma, Ram and Trepat, Xavier and Del Pozo, Miguel A and Parton, Robert G and Rao, Madan and Pullarkat, Pramod and Roca-Cusachs, Pere and Mayor, Satyajit} } @article {36103, title = {The Mechanosensory-Motor Apparatus of Antennae in the Oleander hawk moth (Daphnis nerii, Lepidoptera).}, journal = {J Comp Neurol}, year = {2018}, month = {2018 Jun 15}, abstract = {

Insect antennae are sensory organs of great importance because they can sense diverse environmental stimuli. In addition to serving as primary olfactory organs of insects, antennae also sense a wide variety of mechanosensory stimuli, ranging from low-frequency airflow or gravity cues to high-frequency antennal vibrations due to sound, flight or touch. The basal segments of the antennae house multiple types of mechanosensory structures that prominently include the sensory hair plates, or B{\"o}hm{\textquoteright}s bristles, which measure the gross extent of antennal movement, and a ring of highly sensitive scolopidial neurons, collectively called the Johnston{\textquoteright}s organs, which record subtle flagellar vibrations. To fulfil their multifunctional mechanosensory role, the antennae of insects must actively move thereby enhancing their ability to sense various cues in the surrounding environment. This tight coupling between antennal mechanosensory function and antennal movements means that the underlying mechanosensory-motor apparatus constitutes a highly tuned feedback-controlled system. Our study aims to explore how the sensory and motor components of this system are configured to enable such functional versatility. We describe antennal mechanosensory neurons, their central projections in the brain relative to antennal motor neurons and the internal morphology of various antennal muscles that actuate the basal segments of the antenna. We studied these in the Oleander hawk moth (Daphnis nerii) using a combination of techniques such as neural dye fills, confocal microscopy, scanning electron microscopy and X-Ray tomography. Our study thus provides a detailed anatomical picture of the antennal mechanosensory-motor apparatus, which in turn provides key insights into its multifunctional role. This article is protected by copyright. All rights reserved.

}, issn = {1096-9861}, doi = {10.1002/cne.24477}, author = {Sant, Harshada H and Sane, Sanjay P} } @article {45417, title = {Metabolic adaptations underlying genome flexibility in prokaryotes.}, journal = {PLoS Genet}, volume = {14}, year = {2018}, month = {2018 Oct 29}, pages = {e1007763}, abstract = {

Even across genomes of the same species, prokaryotes exhibit remarkable flexibility in gene content. We do not know whether this flexible or "accessory" content is mostly neutral or adaptive, largely due to the lack of explicit analyses of accessory gene function. Here, across 96 diverse prokaryotic species, I show that a considerable fraction (~40\%) of accessory genomes harbours beneficial metabolic functions. These functions take two forms: (1) they significantly expand the biosynthetic potential of individual strains, and (2) they help reduce strain-specific metabolic auxotrophies via intra-species metabolic exchanges. I find that the potential of both these functions increases with increasing genome flexibility. Together, these results are consistent with a significant adaptive role for prokaryotic pangenomes.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1007763}, author = {Goyal, Akshit} } @article {32024, title = {Micro-habitat distribution drives patch quality for sub-tropical rocky plateau amphibians in the northern Western Ghats, India.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0194810}, abstract = {

The importance of patch quality for amphibians is frequently overlooked in distribution models. Here we demonstrate that it is highly important for the persistence of endemic and endangered amphibians found in the threatened and fragile ecosystems that are the rocky plateaus in Western Maharashtra, India. These plateaus are ferricretes of laterite and characterise the northern section of the Western Ghats/Sri Lanka Biodiversity Hotspot, the eighth most important global hotspot and one of the three most threatened by population growth. We present statistically supported habitat associations for endangered and data-deficient Indian amphibians, demonstrating significant relationships between individual species and their microhabitats. Data were collected during early monsoon across two seasons. Twenty-one amphibian taxa were identified from 14 lateritic plateaus between 67 and 1179m above sea level. Twelve of the study taxa had significant associations with microhabitats using a stepwise analysis of the AICc subroutine (distLM, Primer-e, v7). Generalist taxa were associated with increased numbers of microhabitat types. Non-significant associations are reported for the remaining 9 taxa. Microhabitat distribution was spatially structured and driven by climate and human activity. Woody plants were associated with 44\% of high-elevation taxa. Of the 8 low-elevation taxa 63\% related to water bodies and 60\% of those were associated with pools. Rock size and abundance were important for 33\% of high elevation specialists. Three of the 4 caecilians were associated with rocks in addition to soil and stream presence. We conclude the plateaus are individualistic patches whose habitat quality is defined by their microhabitats within climatic zones.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0194810}, author = {Thorpe, Christopher J and Lewis, Todd R and Kulkarni, Siddharth and Watve, Aparna and Gaitonde, Nikhil and Pryce, David and Davies, Lewis and Bilton, David T and Knight, Mairi E} } @article {28068, title = {Mimicry in butterflies: co-option and a bag of magnificent developmental genetic tricks.}, journal = {Wiley Interdiscip Rev Dev Biol}, volume = {7}, year = {2018}, month = {2018 Jan}, abstract = {

Butterfly wing patterns are key adaptations that are controlled by remarkable developmental and genetic mechanisms that facilitate rapid evolutionary change. With swift advancements in the fields of genomics and genetic manipulations, identifying the regulators of wing development and mimetic wing patterns has become feasible even in nonmodel organisms such as butterflies. Recent mapping and gene expression studies have identified single switch loci of major effects such as transcription factors and supergenes as the main drivers of adaptive evolution of mimetic and polymorphic butterfly wing patterns. We highlight several of these examples, with emphasis on doublesex, optix, WntA and other dynamic, yet essential, master regulators that control critical color variation and sex-specific traits. Co-option emerges as a predominant theme, where typically embryonic and other early-stage developmental genes and networks have been rewired to regulate polymorphic and sex-limited mimetic wing patterns in iconic butterfly adaptations. Drawing comparisons from our knowledge of wing development in Drosophila, we illustrate the functional space of genes that have been recruited to regulate butterfly wing patterns. We also propose a developmental pathway that potentially results in dorsoventral mismatch in butterfly wing patterns. Such dorsoventrally mismatched color patterns modulate signal components of butterfly wings that are used in intra- and inter-specific communication. Recent advances-fuelled by RNAi-mediated knockdowns and CRISPR/Cas9-based genomic edits-in the developmental genetics of butterfly wing patterns, and the underlying biological diversity and complexity of wing coloration, are pushing butterflies as an emerging model system in ecological genetics and evolutionary developmental biology. WIREs Dev Biol 2018, 7:e291. doi: 10.1002/wdev.291 This article is categorized under: Gene Expression and Transcriptional Hierarchies \> Regulatory Mechanisms Comparative Development and Evolution \> Regulation of Organ Diversity Comparative Development and Evolution \> Evolutionary Novelties.

}, issn = {1759-7692}, doi = {10.1002/wdev.291}, author = {Deshmukh, Riddhi and Baral, Saurav and Gandhimathi, A and Kuwalekar, Muktai and Kunte, Krushnamegh} } @article {39420, title = {A minimal "push-pull" bistability model explains oscillations between quiescent and proliferative cell states.}, journal = {Mol Biol Cell}, year = {2018}, month = {2018 Jul 25}, pages = {mbcE18010017}, abstract = {

A minimal model for oscillating between quiescent and growth/proliferation states, dependent on the availability of a central metabolic resource, is presented. From the yeast metabolic cycles (YMCs), metabolic oscillations in oxygen consumption are represented as transitions between quiescent and growth states. We consider metabolic resource availability, growth rates, and switching rates (between states) to model a relaxation oscillator explaining transitions between these states. This frustrated bistability model reveals a required communication between the metabolic resource that determines oscillations, and the quiescent and growth state cells. Cells in each state reflect memory, or hysteresis of their current state, and "push-pull" cells from the other state. Finally, a parsimonious argument is made for a specific central metabolite as the controller of switching between quiescence and growth states. We discuss how an oscillator built around the availability of such a metabolic resource is sufficient to generally regulate oscillations between growth and quiescence, through committed transitions.

}, issn = {1939-4586}, doi = {10.1091/mbc.E18-01-0017}, author = {Krishna, Sandeep and Laxman, Sunil} } @article {34252, title = {Molecular characterization of a new begomovirus infecting Synedrella nodiflora in South India.}, journal = {Arch Virol}, year = {2018}, month = {2018 May 09}, abstract = {

Begomoviruses (family Geminiviridae) cause important diseases in many crops. In addition, many wild plants are reservoirs of begomoviruses, which are a potential menace for nearby crops. A novel begomovirus was isolated from a weed of the species Synedrella nodiflora (Compositae) exhibiting yellow vein symptoms in South India. This virus had a typical monopartite Old World begomovirus genome and was accompanied by a betasatellite. Sequence comparison revealed that this virus represents a new species in the genus Begomovirus. Recombination analysis showed that the novel begomovirus originated through recombination between the begomoviruses ageratum yellow vein Sri Lanka virus and tomato leaf curl Sri Lanka virus.

}, issn = {1432-8798}, doi = {10.1007/s00705-018-3861-3}, author = {Das, Soumita and Hegde, Akshay and Shivaprasad, P V} } @article {36264, title = {A molecular phylogeny of the cicadas (Hemiptera: Cicadidae) with a review of tribe and subfamily classification}, journal = {ZOOTAXA}, volume = {4424}, year = {2018}, month = {05/2018}, pages = {1-64 }, abstract = {

A molecular phylogeny and a review of family-group classification are presented for 137 species (ca. 125 genera) of the insect family Cicadidae, the true cicadas, plus two species of hairy cicadas (Tettigarctidae) and two outgroup species from Cercopidae. Five genes, two of them mitochondrial, comprise the 4992 base-pair molecular dataset. Maximum-likelihood and Bayesian phylogenetic results are shown, including analyses to address potential base composition bias. Tettigarcta is confirmed as the sister-clade of the Cicadidae and support is found for three subfamilies identified in an earlier morphological cladistic analysis. A set of paraphyletic deep-level clades formed by African genera are together named as Tettigomyiinae n. stat. Taxonomic reassignments of genera and tribes are made where morphological examination confirms incorrect placements suggested by the molecular tree, and 11 new tribes are defined (Arenopsaltriini n. tribe, Durangonini n. tribe, Katoini n. tribe, Lacetasini n. tribe, Macrotristriini n. tribe, Malagasiini n. tribe, Nelcyndanini n. tribe, Pagiphorini n. tribe, Pictilini n. tribe, Psaltodini n. tribe, and Selymbriini n. tribe). Tribe Tacuini n. syn. is synonymized with Cryptotympanini, and Tryellina n. syn. is synonymized with an expanded Tribe Lamotialnini. Tribe Hyantiini n. syn. is synonymized with Fidicinini. Tribe Sinosenini is transferred to Cicadinae from Cicadettinae, Cicadatrini is moved to Cicadettinae from Cicadinae, and Ydiellini and Tettigomyiini are transferred to Tettigomyiinae n. stat from Cicadettinae. While the subfamily Cicadinae, historically defined by the presence of timbal covers, is weakly supported in the molecular tree, high taxonomic rank is not supported for several earlier clades based on unique morphology associated with sound production.

}, doi = {10.11646/zootaxa.4424.1.1 }, author = {Marshall, DC and Moulds, M and Hill, KBR and Price, BW and Wade, EJ and Owen, CL and Goemans, G and Marathe, K and Sarkar, V and Cooley, JR and Sanborn, AF and Kunte, Krushnamegh and Villet, MH and Simon, C} } @article {45308, title = {A multi-component neuronal response encodes the larval decision to pupariate upon amino acid starvation.}, journal = {J Neurosci}, year = {2018}, month = {2018 Oct 09}, abstract = {

Organisms need to co-ordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In , growth occurs during larval development. Larvae are thus critically dependant on nutritional inputs but post critical weight they pupariate even when starved. How nutrient availability is coupled to the internal metabolic state for the decision to pupariate needs better understanding. We had earlier identified glutamatergic interneurons in the ventral ganglion that regulate pupariation on a protein-deficient diet. Here we report that third instar larvae (either sex) sense arginine to evaluate their nutrient environment using an amino-acid transporter Slimfast. The glutamatergic interneurons integrate external protein availability with internal metabolic state through neuropeptide signals. IP mediated calcium release and store-operated calcium entry are essential in these glutamatergic neurons for such integration and alter neuronal function by reducing the expression of multiple ion channels.Co-ordinating growth with development, in the context of nutrient availability is a challenge for all organisms in nature. Post attainment of "critical weight" insect larvae can pupariate even in the absence of nutrition. Mechanism(s) that stimulate appropriate cellular responses and allow normal development on a nutritionally deficient diet remain to be understood. Here, we demonstrate that nutritional deprivation, in post-critical weight larvae, is sensed by special sensory neurons through an amino acid transporter that detects loss of environmental arginine. This information is integrated by glutamatergic interneurons with the internal metabolic state through neuropeptide signals. These glutamatergic interneurons require calcium-signalling regulated expression of a host of neuronal channels to generate complex calcium signals essential for pupariation on a protein-deficient diet.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.1163-18.2018}, author = {Jayakumar, Siddharth and Richhariya, Shlesha and Deb, Bipan Kumar and Hasan, Gaiti} } @article {48891, title = {Multiple Sequence Alignments Enhance Boundary Definition of RNA Structures.}, journal = {Genes (Basel)}, volume = {9}, year = {2018}, month = {2018 Dec 04}, abstract = {

Self-contained structured domains of RNA sequences have often distinct molecular functions. Determining the boundaries of structured domains of a non-coding RNA (ncRNA) is needed for many ncRNA gene finder programs that predict RNA secondary structures in aligned genomes because these methods do not necessarily provide precise information about the boundaries or the location of the RNA structure inside the predicted ncRNA. Even without having a structure prediction, it is of interest to search for structured domains, such as for finding common RNA motifs in RNA-protein binding assays. The precise definition of the boundaries are essential for downstream analyses such as RNA structure modelling, e.g., through covariance models, and RNA structure clustering for the search of common motifs. Such efforts have so far been focused on single sequences, thus here we present a comparison for boundary definition between single sequence and multiple sequence alignments. We also present a novel approach, named RNAbound, for finding the boundaries that are based on probabilities of evolutionarily conserved base pairings. We tested the performance of two different methods on a limited number of Rfam families using the annotated structured RNA regions in the human genome and their multiple sequence alignments created from 14 species. The results show that multiple sequence alignments improve the boundary prediction for branched structures compared to single sequences independent of the chosen method. The actual performance of the two methods differs on single hairpin structures and branched structures. For the RNA families with branched structures, including transfer RNA (tRNA) and small nucleolar RNAs (snoRNAs), RNAbound improves the boundary predictions using multiple sequence alignments to median differences of -6 and -11.5 nucleotides (nts) for left and right boundary, respectively (window size of 200 nts).

}, issn = {2073-4425}, doi = {10.3390/genes9120604}, author = {Sabarinathan, Radhakrishnan and Anthon, Christian and Gorodkin, Jan and Seemann, Stefan E} } @article {39422, title = {Multiple stable states in microbial communities explained by the stable marriage problem.}, journal = {ISME J}, year = {2018}, month = {2018 Jul 19}, abstract = {

Experimental studies of microbial communities routinely reveal that they have multiple stable states. While each of these states is generally resilient, certain perturbations such as antibiotics, probiotics, and diet shifts, result in transitions to other states. Can we reliably both predict such stable states as well as direct and control transitions between them? Here we present a new conceptual model-inspired by the stable marriage problem in game theory and economics-in which microbial communities naturally exhibit multiple stable states, each state with a different species{\textquoteright} abundance profile. Our model{\textquoteright}s core ingredient is that microbes utilize nutrients one at a time while competing with each other. Using only two ranked tables, one with microbes{\textquoteright} nutrient preferences and one with their competitive abilities, we can determine all possible stable states as well as predict inter-state transitions, triggered by the removal or addition of a specific nutrient or microbe. Further, using an example of seven Bacteroides species common to the human gut utilizing nine polysaccharides, we predict that mutual complementarity in nutrient preferences enables these species to coexist at high abundances.

}, issn = {1751-7370}, doi = {10.1038/s41396-018-0222-x}, author = {Goyal, Akshit and Dubinkina, Veronika and Maslov, Sergei} } @article {45445, title = {Multi-proxy evidence for an arid shift in the climate and vegetation of the Banni grasslands of western India during the mid- to late-Holocene}, journal = {Holocene}, volume = {28}, year = {2018}, month = {07/2018}, pages = {10572-1070}, abstract = {

Tropical semi-arid grasslands are a widespread and ecologically and economically important terrestrial biome. Here, we use paleoecology to understand woodland{\textendash}grassland transitions across the mid- to late-Holocene period in the Banni grassland, western India. Multi proxy analyses involving palynology, phytoliths and elemental geochemistry were carried out on two sediment cores retrieved from wetlands (Chachi and Luna), to understand temporal fluctuations in vegetation, moisture availability and other environmental parameters. Based on the results, the Chachi core was divided into two major climatic phases. Phase 1 (4600{\textendash}2500 cal. yr BP) was characterised by high precipitation and abundance of pollen types and phytolith morphotypes that indicate the presence of woody savanna, and mesic herbaceous taxa. Phase 2 (2500 cal. yr BP to the present) was characterised by lower precipitation, lower abundance of mesic taxa and an increase in grass phytolith abundance. However, the period from ~1000 cal. yr BP to the present was characterised by the increased abundance of leguminous taxa, dryland herbs/shrubs and a decline in grass phytolith abundance. The Luna core (~1000 cal. yr BP to the present) also showed results matching with the Chachi core for this latter period. Overall, moisture availability in the ecosystem appears to have declined since 4600 cal. yr BP, and the vegetation has responded to this. Although the balance between tree, shrub and grass elements has fluctuated, overall, the region has remained as an open {\textquoteleft}grass and shrub savanna{\textquoteright} with sparse woody vegetation throughout this period. Our study provides insights into the vegetation dynamics and environmental settings in a poorly understood tropical arid-grassland ecosystem from Asia during the mid-late-Holocene.

}, doi = {10.1177/0959683618761540}, author = {Pillai, AAS and Anoop, A and Prasad, V} } @article {45428, title = {Multiresolution-based weighted regularization for denoised image interpolation from scattered samples with application to confocal microscopy }, journal = {Journal of the Optical Society of America A}, volume = {35}, year = {2018}, month = {10/2018}, pages = {1749-1759}, abstract = {

The problem of reconstructing an image from nonuniformly spaced, spatial point measurements is frequently encountered in bioimaging and other scientific disciplines. The most successful class of methods in handling this problem uses the regularization approach involving the minimization of a derivative-based roughness functional. It has been well demonstrated, in the presence of noise, that nonquadratic roughness functionals such as l1 measure yield better performance compared to the quadratic ones in inverse problems in general and in deconvolution in particular. However, for the present problem, all well-evaluated methods use quadratic roughness measures; indeed, l1 performs worse than the quadratic roughness when the sampling density is low. This is due to the fact that the mutual incoherence between the measurement operator (dirac-delta) and the regularization operator (derivative) is low in the present problem. Here we develop a new multiresolution-based roughness functional that performs better than l1 and quadratic functionals under a wide range of sampling densities. We also propose an efficient iterative method for minimizing the resulting cost function. We demonstrate the superiority of the proposed regularization functional in the context of reconstructing full images from nonuniformly undersampled data obtained from a confocal microscope.

}, doi = {10.1364/JOSAA.35.001749}, author = {Francis, B and Mathew, Manoj and Arigovindan, M.} } @article {30436, title = {Mutation burden profile in familial Alzheimer{\textquoteright}s disease cases from India.}, journal = {Neurobiol Aging}, volume = {64}, year = {2018}, month = {2018 Apr}, pages = {158.e7-158.e13}, abstract = {

This study attempts to identify coding risk variants in genes previously implicated in Alzheimer{\textquoteright}s disease (AD) pathways, through whole-exome sequencing of subjects (N\ = 17) with AD, with a positive family history of dementia (familial AD). We attempted to evaluate the mutation burden in genes encoding amyloid precursor protein metabolism and previously linked to risk of dementias. Novel variants were identified in genes involved in amyloid precursor protein metabolism such as PSEN1 (chr 14:73653575, W161C, tgg \> tgT), PLAT (chr 8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden assessment of dementia-related genes for all 17 cases revealed 45 variants, which were either shared across subjects, or were present in just the 1 patient. The study shows that the clinical characteristics, and genetic correlates, obtained in this sample are broadly comparable to the other studies that have investigated familial forms of AD. Our study identifies rare deleterious genetic variations, in the coding region of genes involved in amyloid signaling, and other dementia-associated pathways.

}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2017.12.002}, author = {Syama, Adhikarla and Sen, Somdatta and Kota, Lakshmi Narayanan and Viswanath, Biju and Purushottam, Meera and Varghese, Mathew and Jain, Sanjeev and Panicker, Mitradas M and Mukherjee, Odity} } @article {31051, title = {Nanoplanktonic diatoms are globally overlooked but play a role in spring blooms and carbon export.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 Mar 05}, pages = {953}, abstract = {

Diatoms are one of the major primary producers in the ocean, responsible annually for ~20\% of photosynthetically fixed COon Earth. In oceanic models, they are typically represented as large (\>20 {\textmu}m) microphytoplankton. However, many diatoms belong to the nanophytoplankton (2-20 {\textmu}m) and a few species even overlap with the picoplanktonic size-class (\<2 {\textmu}m). Due to their minute size and difficulty of detection they are poorly characterized. Here we describe a massive spring bloom of the smallest known diatom (Minidiscus) in the northwestern Mediterranean Sea. Analysis of Tara Oceans data, together with literature review, reveal a general oversight of the significance of these small diatoms at the global scale. We further evidence that they can reach the seafloor at high sinking rates, implying the need to revise our classical binary vision of pico- and nanoplanktonic cells fueling the microbial loop, while only microphytoplankton sustain secondary trophic levels and carbon export.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-03376-9}, author = {Leblanc, Karine and Qu{\'e}guiner, Bernard and Diaz, Fr{\'e}d{\'e}ric and Cornet, V{\'e}ronique and Michel-Rodriguez, M{\'o}nica and Durrieu de Madron, Xavier and Bowler, Chris and Malviya, Shruti and Thyssen, Melilotus and Gr{\'e}gori, G{\'e}rald and Rembauville, Mathieu and Grosso, Olivier and Poulain, Julie and de Vargas, Colomban and Pujo-Pay, Mireille and Conan, Pascal} } @article {30155, title = {Neobodonids are dominant kinetoplastids in the global ocean.}, journal = {Environ Microbiol}, volume = {20}, year = {2018}, month = {2018 Feb}, pages = {878-889}, abstract = {

Kinetoplastid flagellates comprise basal mostly free-living bodonids and derived obligatory parasitic trypanosomatids, which belong to the best-studied protists. Due to their omnipresence in aquatic environments and soil, the bodonids are of ecological significance. Here, we present the first global survey of marine kinetoplastids and compare it with the strikingly different patterns of abundance and diversity in their sister clade, the diplonemids. Based on analysis of 18S rDNA V9 ribotypes obtained from 124 sites sampled during the Tara Oceans expedition, our results show generally low to moderate abundance and diversity of planktonic kinetoplastids. Although we have identified all major kinetoplastid lineages, 98\% of kinetoplastid reads are represented by neobodonids, namely specimens of the Neobodo and Rhynchomonas genera, which make up 59\% and 18\% of all reads, respectively. Most kinetoplastids have small cell size (0.8-5 {\textmu}m) and tend to be more abundant in the mesopelagic as compared to the euphotic zone. Some of the most abundant operational taxonomic units have distinct geographical distributions, and three novel putatively parasitic neobodonids were identified, along with their potential hosts.

}, issn = {1462-2920}, doi = {10.1111/1462-2920.14034}, author = {Flegontova, Olga and Flegontov, Pavel and Malviya, Shruti and Poulain, Julie and de Vargas, Colomban and Bowler, Chris and Luke{\v s}, Julius and Hor{\'a}k, Ale{\v s}} } @article {33716, title = {Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.}, journal = {Front Neural Circuits}, volume = {12}, year = {2018}, month = {2018}, pages = {25}, abstract = {

All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

}, issn = {1662-5110}, doi = {10.3389/fncir.2018.00025}, author = {Jayakumar, Siddharth and Hasan, Gaiti} } @article {30080, title = { A new cryptic, rupicolous species of Hemidactylus Oken, 1817 (Squamata: Gekkonidae) from Meghamalai, Tamil Nadu, India}, journal = {ZOOTAXA}, volume = {4374}, year = {2018}, month = {01/2018}, pages = {49-70}, abstract = {

A distinct new gecko of the genus Hemidactylus is described from the Meghamalai massif in Tamil Nadu, India. This large sized (average SVL 88.2 +/- 16.0 to at least 112.2 mm), cryptic, rock-dwelling species is superficially similar to its tuberculate South Asian congeners of comparable size, but can be distinguished from them in having 17-19 longitudinal rows of fairly regularly arranged, strongly keeled, striated tubercles with the two most medial parasagittal rows smaller, flatter, strongly keeled and rounded, increasing in size laterally and becoming strongly conical at the flanks; 8-10 and 10-12 subdigital lamellae under the first and fourth digits respectively of both manus and pes; 17-22 femoral pores on each side separated medially by a diastema of 10-11 poreless scales; 11-15 supralabials and 9-14 infralabials. Molecular data supports the distinctiveness of this species and helps ascertain its phylogenetic position within the larger Indian Hemidactylus clade.

}, doi = {10.11646/zootaxa.4374.1.3}, author = {Chaitanya, R. and Lajmi, Aparna and Giri, Varad B.} } @article {48918, title = {A new cryptic species of ground-dwelling Hemidactylus (Squamata: Gekkonidae) from southern India}, journal = {Phyllomedusa}, volume = {17}, year = {2018}, month = {12/2018}, pages = {169-180}, abstract = {

A new cryptic species of ground-dwelling Hemidactylus (Squamata: Gekkonidae) from southern India. Recently collected specimens of a gecko resembling Hemidactylus reticulatus from northern Karnataka State in southwestern India led me to investigate variation in the species with regards to its morphology and molecular divergence. Results based on existing museum material, combined with molecular data for the mitochondrial cytochrome b gene support the presence of cryptic species within the broadly distributed H. reticulatus complex. Here, I describe a new species of Hemidactylus from northern Karnataka as the frst contribution in resolving the species complex. The integration of molecular and morphological data supports the distinctness of the new species described herein.

}, doi = {10.11606/issn.2316-9079.v17i2p169-180}, author = {Mirza, Zeeshan A} } @article {43880, title = {A new genus Gravelyia with two species of the family Nemesiidae (Araneae: Mygalomorphae) from India}, journal = {Acta Arachnologica}, volume = {67}, year = {2018}, month = {08/2018}, pages = {43-48}, abstract = {

Re-examination of the syntypes of Damarchus excavatus Gravely 1921 raised doubts on its generic allocation. A new genus Gravelyia gen. nov. is proposed to accommodate the species. A new combination Gravelyia excavatus (Gravely 1921) comb. nov. is proposed, and a lectotype is designated for the species. Furthermore, a new species Gravelyia striatus sp. nov. is described from West Bengal.

}, doi = {10.2476/asjaa.67.43}, author = {Mirza, Zeeshan A and Mondal, A} } @article {30079, title = {A new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala, southern India}, journal = {ZOOTAXA}, volume = {4374}, year = {2018}, month = {01/2018}, pages = {545-564}, abstract = {

We here describe Sitana attenboroughii sp. nov., a new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala in southern India. The new species morphologically is closer to Sitana visiri Deepak, 2016 (in Deepak et al. 2016a), however, differs in having higher numbers of ventral scales and a comparatively short but richly colored dewlap. Genetically the new species shows affinity to Sitana marudhamneydhal Deepak, Khandekar, Varma \& Chaitanya, 2016 from which it differs in an uncorrected pairwise sequence divergence of 2.2\% for a fragment of mitochondrial Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit 2 gene

}, doi = {10.11646/zootaxa.4374.4.5}, author = {Sadasivan, Kalesh and Ramesh, M. B. and Palot, Muhamed Jafer and Ambekar, Mayuresh and Mirza, Z.A} } @article {36271, title = {Nitrogen fixation ability explains leaf chemistry and arbuscular mycorrhizal responses to fertilization }, journal = {PLANT ECOLOGY }, volume = {219}, year = {2018}, month = {04/2018}, pages = {391-401 }, doi = {10.1007/s11258-018-0803-9 }, author = {Tiruvaimozhi, YV and Varma, V and Sankaran, M} } @article {29628, title = {Odor source localization in complex visual environments by fruit flies.}, journal = {J Exp Biol}, volume = {221}, year = {2018}, month = {2018 Jan 19}, abstract = {

Flying insects routinely forage in complex and cluttered sensory environments. Their search for a food or a pheromone source typically begins with a whiff of odor, which triggers a flight response, eventually bringing the insect near the odor source. However, pinpointing the precise location of an odor source requires use of both visual and olfactory modalities, aided by odor plumes. Here, we investigated odor-tracking behavior in fruit flies (Drosophila melanogaster) presented with low- or high-contrast visual landmarks, either paired with or separate from an attractive odor cue. These experiments were conducted either in a gentle air stream which generated laminar odor plumes or in still air in which odor dissipates uniformly in all directions. Trajectories of flies revealed several novel features of their odor-tracking behavior in addition to those previously documented. First, in both moving and still air, odor-seeking flies rely on the co-occurrence of visual landmarks with olfactory cues to guide them to odorant objects. Second, flies abruptly decelerate upon encountering an odor plume, thereafter steering towards the nearest visual objects that had no inherent salience in the absence of odor. Thus, interception of an attractive odor increases their salience to nearby high-contrast visual landmarks. Third, flies adopt distinct odor-tracking strategies during flight in moving versus still air. Whereas they weave in and out of plumes towards an odor source in airflow, their approach is more incremental in still air. Both strategies are robust and flexible, and enable flies to reliably find odor sources under diverse visual and airflow environments.

}, issn = {1477-9145}, doi = {10.1242/jeb.172023}, author = {Saxena, Nitesh and Natesan, Dinesh and Sane, Sanjay P} } @article {45449, title = {An optimized protocol for large-scale in situ sampling and analysis of volatile organic compounds}, journal = {Ecology and Evolution}, volume = {8}, year = {2018}, month = {06/2018}, pages = {59242-5935}, abstract = {

Chemical ecology is an ever-expanding field with a growing interest in population- and community-level studies. Many such studies are hindered due to lack of an efficient and accelerated protocol for large-scale sampling and analysis of chemical compounds. Here, we present an optimized protocol for such large-scale study of volatiles. A large-scale in situ study to understand role of semiochemicals in variation in mating success of lekking blackbuck was conducted. Suitable methods for sampling and statistical analysis were identified by testing and comparing the efficiencies of available techniques to reduce analysis time while retaining sensitivity and comprehensiveness. Solid-phase extraction using polydimethylsiloxane, analysis using a semiautomated detection of retention time and base peak, and statistical analysis using random forest algorithm were identified as the most efficient methods for large-scale in situ sampling and analysis of volatiles. The protocol for large-scale volatile analysis can facilitate evolutionary and metaecological studies of volatiles in situ from all types of biological samples. The protocol has potential for wider application with the analysis and interpretation methods being suitable for all kinds of semiochemicals, including nonvolatile chemicals.

}, doi = {10.1002/ece3.4138}, author = {Nair, Jyothi and Sanmugam, PV and Karpe, Snehal D and Ramakrishnan, Uma and Olsson, Shannon B} } @article {79777, title = {An optimized protocol for large-scale in situ sampling and analysis of volatile organic compounds }, journal = {Ecology and Evolution}, volume = {8}, year = {2018}, month = {06/2018}, pages = {5924-5936}, abstract = {

Chemical ecology is an ever-expanding field with a growing interest in population- and community-level studies. Many such studies are hindered due to lack of an efficient and accelerated protocol for large-scale sampling and analysis of chemical compounds. Here, we present an optimized protocol for such large-scale study of volatiles. A large-scale in situ study to understand role of semiochemicals in variation in mating success of lekking blackbuck was conducted. Suitable methods for sampling and statistical analysis were identified by testing and comparing the efficiencies of available techniques to reduce analysis time while retaining sensitivity and comprehensiveness. Solid-phase extraction using polydimethylsiloxane, analysis using a semiautomated detection of retention time and base peak, and statistical analysis using random forest algorithm were identified as the most efficient methods for large-scale in situ sampling and analysis of volatiles. The protocol for large-scale volatile analysis can facilitate evolutionary and metaecological studies of volatiles in situ from all types of biological samples. The protocol has potential for wider application with the analysis and interpretation methods being suitable for all kinds of semiochemicals, including nonvolatile chemicals.

}, doi = {10.1002/ece3.4138}, author = {Nair, Jyothi and Pragadheesh, V S and Karpe, Snehal D and Ramakrishnan, Uma and Olsson, SB} } @article {43845, title = {The Osmolyte TMAO Modulates Protein Folding Cooperativity by Altering Global Protein Stability.}, journal = {Biochemistry}, year = {2018}, month = {2018 Sep 24}, abstract = {

The folding of many globular proteins from the unfolded (U) to the native (N) state appears to be describable by a two-state N <-> U model, which has led to the general belief that protein folding occurs in a highly cooperative manner. One reason for the widespread belief in "two-state folding" is that protein folding reactions are invariably studied by ensemble averaging probes and not by probes that can distinguish as well as quantify the multiple conformations that may be present. Consequently, how cooperativity is affected by protein stability, protein sequence, and solvent conditions is poorly understood. In this study, hydrogen exchange coupled to mass spectrometry (HX-MS) of the PI3K SH3 domain was carried out in the presence of a stabilizing osmolyte, trimethylamine N-oxide (TMAO). By showing that HX occurs under the EX1 regime even in the presence of 2 M TMAO, we were able to examine the temporal evolution of the populations of the different conformations present together. A strong link between protein folding cooperativity and protein stability is revealed. Increasing stability is accompanied by an increase in the ruggedness of the free energy landscape as well as diminished cooperativity; the number of amide sites simultaneously opening up their structure decreases with an increase in TMAO concentration. A comparison of the effect of TMAO to that of urea on the intrinsic dynamics of the PI3K SH3 domain indicates that TMAO counteracts the effect of urea not only on protein stability but also on protein folding cooperativity.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.8b00698}, author = {Jethva, Prashant N and Udgaonkar, Jayant B} } @article {32022, title = {PAI1 mediates fibroblast-mast cell interactions in skin fibrosis.}, journal = {J Clin Invest}, year = {2018}, month = {2018 Mar 26}, abstract = {

Fibrosis is a prevalent pathological condition arising from the chronic activation of fibroblasts. This activation results from the extensive intercellular crosstalk mediated by both soluble factors and direct cell-cell connections. Prominent among these are the interactions of fibroblasts with immune cells, in which the fibroblast-mast cell connection, although acknowledged, is relatively unexplored. We have used a Tg mouse model of skin fibrosis, based on expression of the transcription factor Snail in the epidermis, to probe the mechanisms regulating mast cell activity and the contribution of these cells to this pathology. We have discovered that Snail-expressing keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which functions as a chemotactic factor to increase mast cell infiltration into the skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them competent to bind to mast cells. This heterotypic cell-cell adhesion, also observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal activation of both mast cells and fibroblasts, leading to the cascade of events that promote fibrogenesis. Thus, we have identified roles for PAI1 in the multifactorial program of fibrogenesis that expand its functional repertoire beyond its canonical role in plasmin-dependent processes.

}, issn = {1558-8238}, doi = {10.1172/JCI99088}, author = {Pincha, Neha and Hajam, Edries Yousaf and Badarinath, Krithika and Batta, Surya Prakash Rao and Masudi, Tafheem and Dey, Rakesh and Andreasen, Peter and Kawakami, Toshiaki and Samuel, Rekha and George, Renu and Danda, Debashish and Jacob, Paul Mazhuvanchary and Jamora, Colin} } @article {35863, title = {Phospholipid transport protein function at organelle contact sites.}, journal = {Curr Opin Cell Biol}, volume = {53}, year = {2018}, month = {2018 May 30}, pages = {52-60}, abstract = {

Phospholipids are synthesized at the endoplasmic reticulum (ER), the largest membrane bound organelle that forms membrane contact sites (MCS) with almost every other organelle. MCS are locations at which the membrane es of two organelles are closely positioned to provide a microenvironment where proteins in one membrane can interact with the opposite membrane. Thus, MCS provide an ideal location at which lipid transfer proteins (LTPs) can achieve the efficient transfer of individual classes of lipids from the ER to other organelles via non-vesicular transport. Here we provide an overview of emerging findings on the localization and biochemical activity of LTPs at MCS between the ER and other cellular membranes. The localization of LTPs at MCS offers an elegant cell biological solution to tune local lipid composition to ongoing cell physiology.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2018.04.011}, author = {Cockcroft, Shamshad and Raghu, Padinjat} } @article {45430, title = {Physiological stress responses in wild Asian elephants Elephas maximus in a human-dominated landscape in the Western Ghats, southern India.}, journal = {Gen Comp Endocrinol}, volume = {266}, year = {2018}, month = {2018 09 15}, pages = {150-156}, abstract = {

Increasing anthropogenic pressures on forests, especially in the tropical regions of the world, have restricted several large mammalian species such as the Asian elephant to fragmented habitats within human-dominated landscapes. In this study, we assessed the effects of an anthropogenic landscape and its associated conflict with humans on the physiological stress responses displayed by Asian elephants in the Anamalai Hills of the Western Ghats mountains in south India. We have quantified faecal glucocorticoid metabolite (FGM) concentrations in focal individual elephants within and across herds, inhabiting both anthropogenic and natural habitats, and evaluated their physiological responses to different socio-ecological situations between November 2013 and April 2014. Physiological stress responses varied significantly among the tested elephant age- and sex categories but not across different types of social organisation. Adults generally showed higher FGM concentrations, even in the absence of stressors, than did any other age category. Males also appeared to have higher stress responses than did females. Although there was no significant variation in mean stress levels between elephants on the plateau in the absence of human interactions and those in adjacent, relatively undisturbed forest habitats, FGM concentrations increased significantly for adult and subadult individuals as well as for calves following drives, during which elephants were driven off aggressively by people. Our study emphasises the general importance of understanding individual variation in physiology and behaviour within a population of a seriously threatened mammalian species, the Asian elephant, and specifically highlights the need for long-term monitoring of the stress physiology and behavioural responses of individual elephants across both human-dominated and natural landscapes. Such studies would not only provide comprehensive insights into the adaptive biology of elephants in changing ecological regimes but also aid in the development of effective management and conservation strategies for endangered populations of the species.

}, keywords = {Animals, Animals, Wild, Elephants, Feces, Female, Forests, Geography, Glucocorticoids, Humans, India, Linear Models, Male, Metabolome, Models, Biological, Stress, Physiological}, issn = {1095-6840}, doi = {10.1016/j.ygcen.2018.05.009}, author = {Vijayakrishnan, Sreedhar and Kumar, Mavatur Ananda and Umapathy, G and Kumar, Vinod and Sinha, Anindya} } @article {36663, title = {Playing it safe? Behavioural responses of mosquito larvae encountering a fish predator }, journal = {ETHOLOGY ECOLOGY \& EVOLUTION}, volume = {30}, year = {2018}, month = {2018}, pages = {70-87 }, doi = {10.1080/03949370.2017.1313785 }, author = {Chandrasegaran, K and Singh, A and Laha, M and Quader, S} } @article {29620, title = {Probing subtle conformational changes induced by phosphorylation and point mutations in the TIR domains of TLR2 and TLR3.}, journal = {Proteins}, year = {2018}, month = {2018 Jan 31}, abstract = {

Extensive research performed on Toll-like receptor (TLR) signalling has identified residues in the Toll/interleukin-1 receptor (TIR) domains that are essential for its proper functioning. Among these residues, those in BB loop are particularly significant as single amino acid mutations in this region can cause drastic changes in downstream signalling. However, while the effect of these mutations on the function is well studied (like the P681H mutation in TLR2, the A795P mutation in TLR3, and the P714H mutation in TLR4), their influence on the dynamics and inter-residue networks is not well understood. The effects of local perturbations induced by these mutations could propagate throughout the TIR domain, influencing interactions with other TIR domain-containing proteins. The identification of these subtle changes in inter-residue interactions can provide new insights and structural rationale for how single-point mutations cause drastic changes in TIR-TIR interactions. We employed molecular dynamics simulations and protein structure network (PSN) analyses to investigate the structural transitions with special emphasis on TLR2 and TLR3. Our results reveal that phosphorylation of the Tyr 759 residue in the TIR domain of TLR3 introduces rigidity to its BB loop. Subtle differences in the intra BB loop hydrogen bonding network between TLR3 and TLR2 are also observed. The PSN analyses indicate that the TIR domain is highly connected and pinpoints key differences in the inter-residue interactions between the wild-type and mutant TIR domains, suggesting that TIR domain structure is prone to allosteric effects, consistent with the current view of the influence of allostery on TLR signaling. This article is protected by copyright. All rights reserved.

}, issn = {1097-0134}, doi = {10.1002/prot.25471}, author = {Mahita, Jarjapu and Sowdhamini, Ramanathan} } @article {29627, title = {Protein kinase D regulates metabolism and growth by controlling secretion of insulin like peptide.}, journal = {Dev Biol}, volume = {434}, year = {2018}, month = {2018 Feb 01}, pages = {175-185}, abstract = {

Mechanisms coupling growth and metabolism are conserved in Drosophila and mammals. In metazoans, such coupling is achieved across tissue scales through the regulated secretion of chemical messengers such as insulin that control the metabolism and growth of cells. Although the regulated secretion of Insulin like peptide (dILP) is key to normal growth and metabolism in Drosophila, the sub-cellular mechanisms that regulate dILP release remain poorly understood. We find that reduced function of the only protein kinase D in Drosophila (dPKDH) results in delayed larval growth and development associated with abnormal sugar and lipid metabolism, reduced insulin signalling and accumulation of dILP2 in the neurosecretory IPCs of the larval brain. These phenotypes are rescued by tissue-selective reconstitution of dPKD in the neurosecretory cells of dPKDH. Selective downregulation of dPKD activity in the neurosecretory IPCs phenocopies the growth defects, metabolic abnormalities and dILP2 accumulation seen in dPKDH. Thus, dPKD mediated secretion of dILP2 from neurosecretory cells during development is necessary for normal larval growth.

}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2017.12.008}, author = {Ashe, Sudipta and Malhotra, Vivek and Raghu, Padinjat} } @article {34070, title = {Quantitative Control of GPCR Organization and Signaling by Endocytosis in Epithelial Morphogenesis.}, journal = {Curr Biol}, year = {2018}, month = {2018 Apr 25}, abstract = {

Tissue morphogenesis arises from controlled cell deformations in response to cellular contractility. During Drosophila gastrulation, apical activation of the actomyosin networks drives apical constriction in the invaginating mesoderm and cell-cell intercalation in the extending ectoderm. Myosin II (MyoII) is activated by cell-surface G protein-coupled receptors (GPCRs), such as Smog and Mist, that activate G proteins, the small GTPase Rho1, and the kinase Rok. Quantitative control over GPCR and Rho1 activation underlies differences in deformation of mesoderm and ectoderm cells. We show that GPCR Smog activity is concentrated on two different apical plasma membrane compartments, i.e., the surface and plasma membrane invaginations. Using fluorescence correlation spectroscopy, we probe the surface of the plasma membrane, and we show that Smog homo-clusters in response to its activating ligand Fog. Endocytosis of Smog is regulated by the kinase Gprk2 and β-arrestin-2 that clears active Smog from the plasma membrane. When Fog concentration is high or endocytosis is low, Smog rearranges in homo-clusters and accumulates in plasma membrane invaginations that are hubs for Rho1 activation. Lastly, we find higher Smog homo-cluster concentration and numerous apical plasma membrane invaginations in the mesoderm compared to the ectoderm, indicative of reduced endocytosis. We identify that dynamic partitioning of active Smog at the surface of the plasma membrane or plasma membrane invaginations has a direct impact on Rho1 signaling. Plasma membrane invaginations accumulate high Rho1-guanosine triphosphate (GTP) suggesting they form signaling centers. Thus, Fog concentration and Smog endocytosis form coupled regulatory processes that regulate differential Rho1 and MyoII activation in the Drosophila embryo.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2018.03.068}, author = {Jha, Ankita and van Zanten, Thomas S and Philippe, Jean-Marc and Mayor, Satyajit and Lecuit, Thomas} } @article {39427, title = {A random first-order transition theory for an active glass.}, journal = {Proc Natl Acad Sci U S A}, volume = {115}, year = {2018}, month = {2018 Jul 24}, pages = {7688-7693}, abstract = {

How does nonequilibrium activity modify the approach to a glass? This is an important question, since many experiments reveal the near-glassy nature of the cell interior, remodeled by activity. However, different simulations of dense assemblies of active particles, parametrized by a self-propulsion force, [Formula: see text], and persistence time, [Formula: see text], appear to make contradictory predictions about the influence of activity on characteristic features of glass, such as fragility. This calls for a broad conceptual framework to understand active glasses; here, we extend the random first-order transition (RFOT) theory to a dense assembly of self-propelled particles. We compute the active contribution to the configurational entropy through an effective model of a single particle in a caging potential. This simple active extension of RFOT provides excellent quantitative fits to existing simulation results. We find that whereas [Formula: see text] always inhibits glassiness, the effect of [Formula: see text] is more subtle and depends on the microscopic details of activity. In doing so, the theory automatically resolves the apparent contradiction between the simulation models. The theory also makes several testable predictions, which we verify by both existing and new simulation data, and should be viewed as a step toward a more rigorous analytical treatment of active glass.

}, issn = {1091-6490}, doi = {10.1073/pnas.1721324115}, author = {Nandi, Saroj Kumar and Mandal, Rituparno and Bhuyan, Pranab Jyoti and Dasgupta, Chandan and Rao, Madan and Gov, Nir S} } @article {28566, title = {RDGBα localization and function at membrane contact sites is regulated by FFAT-VAP interactions.}, journal = {J Cell Sci}, volume = {131}, year = {2018}, month = {2018 Jan 08}, abstract = {

Phosphatidylinositol transfer proteins (PITPs) are essential regulators of PLC signalling. The PI transfer domain (PITPd) of multi-domain PITPs is reported to be sufficient for in vivo function, questioning the relevance of other domains in the protein. In Drosophila photoreceptors, loss of RDGBα, a multi-domain PITP localized to membrane contact sites (MCSs), results in multiple defects during PLC signalling. Here, we report that the PITPd of RDGBα does not localize to MCSs and fails to support function during strong PLC stimulation. We show that the MCS localization of RDGBα depends on the interaction of its FFAT motif with dVAP-A. Disruption of the FFAT motif (RDGBFF/AA) or downregulation of dVAP-A, both result in mis-localization of RDGBα and are associated with loss of function. Importantly, the ability of the PITPd in full-length RDGBFF/AA to rescue mutant phenotypes was significantly worse than that of the PITPd alone, indicating that an intact FFAT motif is necessary for PITPd activity in vivo Thus, the interaction between the FFAT motif and dVAP-A confers not only localization but also intramolecular regulation on lipid transfer by the PITPd of RDGBα. This article has an associated First Person interview with the first author of the paper.

}, issn = {1477-9137}, doi = {10.1242/jcs.207985}, author = {Yadav, Shweta and Thakur, Rajan and Georgiev, Plamen and Deivasigamani, Senthilkumar and Krishnan, Harini and Ratnaparkhi, Girish and Raghu, Padinjat} } @article {36950, title = {Recovery of Five Complete Influenza A(H1N1)pdm09 Genome Sequences from the 2015 Influenza Outbreak in India by Metagenomic Sequencing.}, journal = {Genome Announc}, volume = {6}, year = {2018}, month = {2018 Jun 28}, abstract = {

Five complete (H1N1)pdm09 viral sequences were recovered from hospitalized individuals during the 2015 influenza outbreak by metagenomic sequencing. Four of the genomes are from oropharyngeal swabs, and one is from an isolate. All five sequences belong to an emerging 6B clade. Studying them further is critical for outbreak preparedness.

}, issn = {2169-8287}, doi = {10.1128/genomeA.00511-18}, author = {Dash, Paban Kumar and Pattabiraman, Chitra and Tandel, Kundan and Sharma, Shashi and Kumar, Jyoti S and Siddappa, Shilpa and Gowda, Malali and Krishna, Sudhir and Parida, Manmohan} } @article {33715, title = {Regulation of Global Transcription in by Rsd and 6S RNA.}, journal = {G3 (Bethesda)}, year = {2018}, month = {2018 Apr 23}, abstract = {

In , the sigma factor σ directs RNA polymerase to transcribe growth-related genes, while σ directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to σ, and the non-coding 6S RNA which binds to the RNA polymerase-σ holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show for the first time that Rsd and 6S RNA facilitate σ activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression.

}, issn = {2160-1836}, doi = {10.1534/g3.118.200265}, author = {Lal, Avantika and Krishna, Sandeep and Seshasayee, Aswin Sai Narain} } @article {38420, title = {Regulation of PI4P levels by PI4KIIIα during G-protein coupled PLC signaling in photoreceptors.}, journal = {J Cell Sci}, year = {2018}, month = {2018 Jul 06}, abstract = {

The activation of phospholipase C (PLC) is a conserved mechanism of receptor activated cell signaling at the plasma membrane. PLC hydrolyzes the minor membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P] and continued signaling requires the resynthesis and availability of PI(4,5)P at the plasma membrane. PI(4,5)P is synthesized by the phosphorylation of phosphatidylinositol-4-phosphate (PI4P). Thus, a continuous supply of PI4P is essential to support ongoing PLC signaling. While the enzyme PI4KA has been identified to perform this function in cultured mammalian cells, its function in the context of an physiological model has not been established. In this study, we show that in photoreceptors, PI4KIIIα activity is required to support signaling during G-protein coupled PLC activation. Depletion of PI4KIIIα results in impaired electrical responses to light and reduced plasma membrane levels of PI4P and PI(4,5)P Depletion of conserved proteins Efr3 and TTC7 that assemble PI4KIIIα at the plasma membrane also results in an impaired light response and reduced plasma membrane PI4P and PI(4,5)P levels. Thus PI4KIIIα activity at the plasma membrane generates PI4P and supports PI(4,5)P levels during receptor activated PLC signaling.

}, issn = {1477-9137}, doi = {10.1242/jcs.217257}, author = {Balakrishnan, Sruthi S and Basu, Urbashi and Shinde, Dhananjay and Thakur, Rajan and Jaiswal, Manish and Raghu, Padinjat} } @article {32023, title = {Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus.}, journal = {Behav Brain Res}, volume = {347}, year = {2018}, month = {2018 Mar 23}, pages = {314-324}, abstract = {

Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors.

}, issn = {1872-7549}, doi = {10.1016/j.bbr.2018.03.034}, author = {Patel, D and Anilkumar, S and Chattarji, S and Buwalda, B} } @article {33713, title = {Reply to Jobling, "Ectopic Expression of the and Genes of the Cryptic Prophage Rac of K-12 May Be Toxic but Do They Really Encode Toxins?: a Case for Using Genetic Context To Understand Function".}, journal = {mSphere}, volume = {3}, year = {2018}, month = {2018 Apr 25}, issn = {2379-5042}, doi = {10.1128/mSphere.00177-18}, author = {Seshasayee, Aswin Sai Narain} } @article {43849, title = {Responses of aerial insectivorous bats to local and landscape-level features of coffee agroforestry systems in Western Ghats, India.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0201648}, abstract = {

Shade coffee has shown great promise in providing crucial habitats for biodiversity outside formal protected areas. Insectivorous bats have been understudied in coffee, although they may provide pest control services. We investigated the influence of local and landscape-level features of coffee farms on aerial insectivorous bats in Chikmagalur district in the Western Ghats biodiversity hotspot, India. Bats were monitored in 20 farm sites using ultrasound detectors, and the response of bat species richness and activity to changes in tree density, proportion of built-up area in the neighborhood, and distance of farm from forest areas quantified. We examined if models built to explain the species richness and activity could also predict them in nine additional sites. We detected nine phonic types/species in the study area. The quantified predictors had no effect on assemblage-level species richness and activity of bats. Responses of edge-space and cluttered-space forager guilds mirrored those of the overall assemblage, but some species vulnerable to forest conversion like Rhinolophus beddomei were detected rarely. Best models explained up to 20\% and 15\% variation in assemblage-level species richness and activity respectively, and were poor predictors of both response variables. We conclude that coffee farms in our study area offer an important commuting space for insectivorous bats across a gradient of shade management. Further research should include species-specific responses to management decisions for at-risk species and quantification of ecosystem services like natural pest control to inform biodiversity conservation initiatives in the Western Ghats coffee landscapes.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0201648}, author = {Ongole, Shasank and Sankaran, Mahesh and Karanth, Krithi K} } @article {45441, title = {Responses of interspecific associations in mixed-species bird flocks to selective logging}, journal = {Journal of Applied Ecology}, volume = {55}, year = {2018}, month = {07/2018}, pages = {1637-1646}, abstract = {

  1. Non-trophic interactions (or, inter-species associations) play a prominent role in determining community structure and function. Mixed-species bird flocks are networks of non-trophic associations that confer foraging and anti-predator benefits to participant species. Yet, the responses of these interspecific associations to anthropogenic environmental changes are poorly understood.

  2. Selective logging is pervasive in the tropics, and can affect associations in mixed-species bird flocks by altering resource availability and/or predation risk, or through the altered abundances of species participating in mixed flocks. Across a gradient of logging intensity, we examined how the number and strength of associations in two different mixed-species flock types responded to logging intensity, while simultaneously controlling statistically for changes in the abundances of species in response to logging.

  3. Across the logging gradient, we used network analyses to: (1) quantify the proportion of potentially realizable associations, and (2) measure the strengths of these realized associations. For both these analyses, we used null models to investigate whether changes in the network properties of mixed flocks were simply abundance-driven, or congruent with expectations of how flock properties might be modified by selective logging.

  4. In understorey flocks, after controlling statistically for changing abundances of participant species, the proportion of realized associations decreased with increasing logging intensity, whereas mean association strength did not show any relation with logging intensity. In midstorey flocks, both the proportion and mean strength of realized associations increased with increasing logging intensity.

  5. Synthesis and applications. By statistically separating abundance and behaviour-mediated effects, we show that interspecific associations in mixed-species bird flocks respond to potential resource and/or predation changes from logging, but that their functional roles persist in logged forest. We show that logged forests can conserve not only community richness, but also function. Thus, these logged forests must be prevented from ongoing conversion into non-forest habitats such as agriculture and plantation.

}, doi = {10.1111/1365-2664.13097}, author = {Borah, B and Quader, Suhel and Srinivasan, U} } @article {45304, title = {Revision of the genus Rustia St{\r a}l, 1866 (Hemiptera: Cicadidae: Cicadinae) including a generic synonymy, four new combinations, and two new species from the Western Ghats, India.}, journal = {Zootaxa}, volume = {4457}, year = {2018}, month = {2018 Aug 09}, pages = {431-443}, abstract = {

The cicada genus Rustia St{\r a}l, 1866 is redescribed. The synonymy of Gudaba Distant, 1906 n. syn. is proposed reassigning the four species of that genus to become Rustia apicata (Distant, 1906) n. comb., Rustia longicauda (Lei, 1996) n. comb., Rustia maculata (Distant, 1912) n. comb., and Rustia marginata (Distant, 1897) n. comb. Two new species, Rustia minuta n. sp. and Rustia kodagura n. sp. that were found during our Indian cicada surveys in the Western Ghats are described. A key for the known species of the genus is provided.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4457.3.5}, author = {Marathe, Kiran and Sanborn, Allen F and Kunte, Krushnamegh} } @article {35149, title = {RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.}, journal = {Neuron}, volume = {98}, year = {2018}, month = {2018 May 16}, pages = {754-766.e4}, abstract = {

Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in\ vitro, are essential for efficient formation of neuronal mRNP assemblies in\ vivo. Remarkably, ΔIDR mutants that lack neuronal RNP granules show normal animal development, survival, and fertility. However, they show defects in long-term memory formation/consolidation as well as in C9ORF72 dipeptide repeat or FUS-induced neurodegeneration. Together, our findings demonstrate (1) that higher-order mRNP assemblies contribute to long-term neuronal plasticity and memory, and (2) that a targeted reduction in RNP-granule formation efficiency can alleviate specific forms of neurodegeneration.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2018.04.032}, author = {Bakthavachalu, Baskar and Huelsmeier, Joern and Sudhakaran, Indulekha P and Hillebrand, Jens and Singh, Amanjot and Petrauskas, Arnas and Thiagarajan, Devasena and Sankaranarayanan, M and Mizoue, Laura and Anderson, Eric N and Pandey, Udai Bhan and Ross, Eric and VijayRaghavan, K and Parker, Roy and Ramaswami, Mani} } @article {48890, title = {The roles of vision and antennal mechanoreception in hawkmoth flight control.}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 12 10}, abstract = {

Flying animals need continual sensory feedback about their body position and orientation for flight control. The visual system provides essential but slow feedback. In contrast, mechanosensory channels can provide feedback at much shorter timescales. How the contributions from these two senses are integrated remains an open question in most insect groups. In Diptera, fast mechanosensory feedback is provided by organs called halteres and is crucial for the control of rapid flight manoeuvres, while vision controls manoeuvres in lower temporal frequency bands. Here, we have investigated the visual-mechanosensory integration in the hawkmoth They represent a large group of insects that use Johnston{\textquoteright}s organs in their antennae to provide mechanosensory feedback on perturbations in body position. Our experiments show that antennal mechanosensory feedback specifically mediates fast flight manoeuvres, but not slow ones. Moreover, we did not observe compensatory interactions between antennal and visual feedback.

}, issn = {2050-084X}, doi = {10.7554/eLife.37606}, author = {Dahake, Ajinkya and St{\"o}ckl, Anna L and Foster, James J and Sane, Sanjay P and Kelber, Almut} } @article {36665, title = {A Route to Direct Fitness: Natural and Experimentally Induced Queen Succession in the Tropical Primitively Eusocial Wasp Ropalidia marginata }, journal = {JOURNAL OF INSECT BEHAVIOR }, volume = {31}, year = {2018}, month = {01/2018}, pages = {54-65 }, doi = {10.1007/s10905-017-9657-6 }, author = {Saha, P and Nandi, AK and Unnikrishnan, S and Shilpa, MC and Shukla, SP and Mandal, S and Mitra, A and Gadagkar, R} } @article {32474, title = {Rudhira/BCAS3 is essential for mouse development and cardiovascular patterning.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 Apr 04}, pages = {5632}, abstract = {

Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein that promotes directional cell migration and angiogenesis in vitro and is implicated in human carcinomas and coronary artery disease. To study the role of Rudhira during development in vivo, we generated the first knockout mouse for rudhira and show that Rudhira is essential for mouse development. Rudhira null embryos die at embryonic day (E) 9.5 accompanied by severe vascular patterning defects in embryonic and extra-embryonic tissues. To identify the molecular processes downstream of rudhira, we analyzed the transcriptome of intact knockout yolk sacs. Genome-wide transcriptome analysis showed that Rudhira functions in angiogenesis and its related processes such as cell adhesion, extracellular matrix organization, peptidase activity and TGFβ signaling. Since Rudhira is also expressed in endothelial cells\ (ECs), we further generated Tie2Cre-mediated endothelial knockout (CKO) of rudhira. CKO embryos survive to E11.5 and similar to the global knockout, display gross vascular patterning defects, showing that endothelial Rudhira is vital for development. Further, Rudhira knockdown ECs in culture fail to sprout in a spheroid-sprouting assay, strongly supporting its role in vascular patterning. Our study identifies an essential role for Rudhira in blood vessel remodeling and provides a mouse model for cardiovascular development.

}, issn = {2045-2322}, doi = {10.1038/s41598-018-24014-w}, author = {Shetty, Ronak and Joshi, Divyesh and Jain, Mamta and Vasudevan, Madavan and Paul, Jasper Chrysolite and Bhat, Ganesh and Banerjee, Poulomi and Abe, Takaya and Kiyonari, Hiroshi and VijayRaghavan, K and Inamdar, Maneesha S} } @article {33712, title = {The Science of Living Matter for Tomorrow.}, journal = {Cell Syst}, volume = {6}, year = {2018}, month = {2018 Apr 25}, pages = {400-402}, issn = {2405-4712}, doi = {10.1016/j.cels.2018.04.003}, author = {Bauer, G and Fakhri, N and Kicheva, A and Kondev, J and Kruse, K and Noji, H and Riveline, D and Saunders, T E and Thattai, M and Wieschaus, E} } @article {36668, title = {Seasonal habitat use in three species of wild ungulates in Sikkim Himalaya }, journal = {MAMMALIAN BIOLOGY }, volume = {88}, year = {2018}, month = {01/2018}, pages = {100-106 }, doi = {10.1016/j.mambio.2017.11.013 }, author = {Srivastava, T and Kumar, A} } @article {39425, title = {SEPT7-mediated regulation of Ca entry through Orai channels requires other septin subunits.}, journal = {Cytoskeleton (Hoboken)}, volume = {76}, year = {2018}, month = {2018 Jul 13}, pages = {104-114}, abstract = {

Orai channels are plasma membrane resident Ca channels that allow extracellular Ca uptake after depletion of ER-Ca stores by a process called store-operated Ca entry (SOCE). Septins of the SEPT2 subgroup act as positive regulators of SOCE in human non-excitable cells. SEPT2 subgroup septins form the central core of hetero-hexameric or hetero-octameric complexes with SEPT6, SEPT7 and SEPT9 subgroup septins. The presence of fewer septin encoding genes coupled with ease of genetic manipulation allows for better understanding of septin subgroup function in Drosophila. Our earlier findings show that although dSEPT7 reduction does not alter Orai-mediated Ca entry during SOCE, it results in constitutive activation of Orai channels in resting neurons. Here we have investigated the role of other septin subgroup members in regulating Orai channel activation in Drosophila neurons by both cellular and functional assays. We show that dSEPT1, a SEPT2 subgroup septin can exist in a complex with dSEPT2 and dSEPT7 in the central nervous system (CNS) of Drosophila. Our findings suggest that the nature of septin filaments and heteromers obtained after reducing septins of different subgroups alters their ability to regulate Orai channel opening. The molecular mechanisms underlying this complex regulation of Orai function by septins require further cellular investigations. This article is protected by copyright. All rights reserved.

}, issn = {1949-3592}, doi = {10.1002/cm.21476}, author = {Deb, Bipan Kumar and Hasan, Gaiti} } @article {29630, title = {Site-specific time-resolved FRET reveals local variations in the unfolding mechanism in an apparently two-state protein unfolding transition.}, journal = {Phys Chem Chem Phys}, volume = {20}, year = {2018}, month = {2018 Jan 31}, pages = {3216-3232}, abstract = {

Protein folding/unfolding transitions between the native (N) and unfolded (U) states are usually describable as two-state, only because of the dominant presence of the N and/or U states, because of which high energy intermediates remain undetected. Delineation of the cooperativity underlying these transitions, and characterization of high energy intermediates that are populated sparsely, have been difficult challenges, especially under equilibrium conditions, and require the use of a sensitive probe that reports on both the structures and population distributions of the partially unfolded intermediates. In this study, the use of multisite time-resolved FRET to monitor structural change in five specific segments of the small protein monellin, has brought out local deviations from two-state behavior during unfolding. It is shown that in some segments of the protein structure, denaturant-induced unfolding proceeds first by gradual expansion of the N state, then by an all-or-none transition from the N state ensemble to the U state ensemble, followed finally by expansion of the U state. Segments encompassing the sole helix appear, however, to unfold completely through a gradual transition from the N to U states. Finally, it is shown that equilibrium unfolding of monellin is not only heterogeneous, but that the degree of non-cooperativity differs between the sole α-helix and different parts of the β-sheet.

}, issn = {1463-9084}, doi = {10.1039/c7cp06214a}, author = {Bhatia, Sandhya and Krishnamoorthy, G and Udgaonkar, Jayant B} } @article {36272, title = {Size-dependent recycling of membrane clusters}, journal = {EPL (Europhysics Letters)}, volume = {121}, year = {2018}, month = {03/2018}, abstract = {

The role of recycling in the control of membrane domains is a contentious issue and currently an open research question. In this context, we study the coarsening of strongly microphase-separated membrane domains in the presence of recycling of material. The dynamics of cluster size distribution is studied under both scale-free and size-dependent recycling. Closed-form solutions to the steady-state distribution and its associated moments are found in both cases. For the size-independent case, the time evolution of the moments is analytically obtained, providing exact results for their corresponding relaxation times. Since these moments and relaxation times are measurable quantities that may be determined by comparison with experimental data, our results provide a framework with which to understand and assess the interplay between membrane recycling and domain formation.

}, doi = {10.1209/0295-5075/121/58004 }, author = {Rautu, SA and Rowlands, G and Turner, MS} } @article {34255, title = {Small GTPases and BAR domain proteins regulate branched actin polymerisation for clathrin and dynamin-independent endocytosis.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 May 09}, pages = {1835}, abstract = {

Using real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42\ which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected. Removal of IRSp53, a negative curvature sensing protein, abolishes CG endocytosis. Furthermore, the identification of ARP2/3 complex at CG endocytic sites, maintained in an inactive state reveals a function for PICK1, an ARP2/3 inhibitor. The spatio-temporal sequence of the arrival and disappearance of the molecules suggest a mechanism for a clathrin and dynamin-independent endocytic process. Coincident with the loss of PICK1 by GBF1-activated ARF1, CDC42 recruitment leads to the activation of IRSp53 and the ARP2/3 complex, resulting in a burst of F-actin polymerisation potentially powering scission.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-03955-w}, author = {Sathe, Mugdha and Muthukrishnan, Gayatri and Rae, James and Disanza, Andrea and Thattai, Mukund and Scita, Giorgio and Parton, Robert G and Mayor, Satyajit} } @article {31393, title = {Social structure of the harem-forming promiscuous fruit bat,, is the harem truly important?}, journal = {R Soc Open Sci}, volume = {5}, year = {2018}, month = {2018 Feb}, pages = {172024}, abstract = {

Bats are social animals and display a diverse variety of mating and social systems, with most species exhibiting some form of polygyny. Their social organization is fluid and individuals frequently switch partners and roosting sites. While harem-like social organization is observed in multiple tropical species, its importance is contested in many of them. In this study, we investigated the role of harems in the social organization of the old world fruit bat. Based on regular behavioural observations over a period of 20 months and genetic data from microsatellite markers, we observed that the social organization is flexible, individuals regularly shift between roosts and the social organization resembles a fission-fusion society. Behavioural and genetic analyses suggest that the harems are not strict units of social structure, and the colony does not show signatures of subdivision with harems as behavioural units. We also observed that there was no correlation between individuals with high association index and pairwise relatedness. Our findings indicate that similar to the mating system, the social organization ofcan also be categorized as a fission-fusion society, and hence the term {\textquoteright}harem{\textquoteright} is a misnomer. We conclude that the social system ofis flexible, with multi-male multi-female organization, and individuals tend to be loyal to a given area rather than a roost.

}, issn = {2054-5703}, doi = {10.1098/rsos.172024}, author = {Garg, Kritika M and Chattopadhyay, Balaji and Ramakrishnan, Uma} } @article {35146, title = {Soft inclusion in a confined fluctuating active gel.}, journal = {Phys Rev E}, volume = {97}, year = {2018}, month = {2018 Mar}, pages = {032602}, abstract = {

We study stochastic dynamics of a point and extended inclusion within a one-dimensional confined active viscoelastic gel. We show that the dynamics of a point inclusion can be described by a Langevin equation with a confining potential and multiplicative noise. Using a systematic adiabatic elimination over the fast variables, we arrive at an overdamped equation with a proper definition of the multiplicative noise. To highlight various features and to appeal to different biological contexts, we treat the inclusion in turn as a rigid extended element, an elastic element, and a viscoelastic (Kelvin-Voigt) element. The dynamics for the shape and position of the extended inclusion can be described by coupled Langevin equations. Deriving exact expressions for the corresponding steady-state probability distributions, we find that the active noise induces an attraction to the edges of the confining domain. In the presence of a competing centering force, we find that the shape of the probability distribution exhibits a sharp transition upon varying the amplitude of the active noise. Our results could help understanding the positioning and deformability of biological inclusions, e.g., organelles in cells, or nucleus and cells within tissues.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.97.032602}, author = {Singh Vishen, Amit and Rupprecht, J-F and Shivashankar, G V and Prost, J and Rao, Madan} } @article {36788, title = {Stable Knockdown in Self-Renewing Human Neural Precursors Promotes Premature Neural Differentiation.}, journal = {Front Mol Neurosci}, volume = {11}, year = {2018}, month = {2018}, pages = {178}, abstract = {

Ca signaling plays a significant role in the development of the vertebrate nervous system where it regulates neurite growth as well as synapse and neurotransmitter specification. Elucidating the role of Ca signaling in mammalian neuronal development has been largely restricted to either small animal models or primary cultures. Here we derived human neural precursor cells (NPCs) from human embryonic stem cells to understand the functional significance of a less understood arm of calcium signaling, Store-operated Ca entry or SOCE, in neuronal development. Human NPCs exhibited robust SOCE, which was significantly attenuated by expression of a stable shRNA-miR targeted toward the SOCE molecule, STIM1. Along with the plasma membrane channel Orai, STIM is an essential component of SOCE in many cell types, where it regulates gene expression. Therefore, we measured global gene expression in human NPCs with and without knockdown. Interestingly, pathways down-regulated through knockdown were related to cell proliferation and DNA replication processes, whereas post-synaptic signaling was identified as an up-regulated process. To understand the functional significance of these gene expression changes we measured the self-renewal capacity of NPCs with knockdown. The knockdown NPCs demonstrated significantly reduced neurosphere size and number as well as precocious spontaneous differentiation toward the neuronal lineage, as compared to control cells. These findings demonstrate that mediated SOCE in human NPCs regulates gene expression changes, that are likely to physiologically modulate the self-renewal and differentiation of NPCs.

}, issn = {1662-5099}, doi = {10.3389/fnmol.2018.00178}, author = {Gopurappilly, Renjitha and Deb, Bipan Kumar and Chakraborty, Pragnya and Hasan, Gaiti} } @article {46415, title = {State space and movement specification in open population spatial capture-recapture models.}, journal = {Ecol Evol}, volume = {8}, year = {2018}, month = {2018 Oct}, pages = {10336-10344}, abstract = {

With continued global changes, such as climate change, biodiversity loss, and habitat fragmentation, the need for assessment of long-term population dynamics and population monitoring of threatened species is growing. One powerful way to estimate population size and dynamics is through capture-recapture methods. Spatial capture (SCR) models for open populations make efficient use of capture-recapture data, while being robust to design changes. Relatively few studies have implemented open SCR models, and to date, very few have explored potential issues in defining these models. We develop a series of simulation studies to examine the effects of the state-space definition and between-primary-period movement models on demographic parameter estimation. We demonstrate the implications on a 10-year camera-trap study of tigers in India. The results of our simulation study show that movement biases survival estimates in open SCR models when little is known about between-primary-period movements of animals. The size of the state-space delineation can also bias the estimates of survival in certain cases.We found that both the state-space definition and the between-primary-period movement specification affected survival estimates in the analysis of the tiger dataset (posterior mean estimates of survival ranged from 0.71 to 0.89). In general, we suggest that open SCR models can provide an efficient and flexible framework for long-term monitoring of populations; however, in many cases, realistic modeling of between-primary-period movements is crucial for unbiased estimates of survival and density.

}, issn = {2045-7758}, doi = {10.1002/ece3.4509}, author = {Gardner, Beth and Sollmann, Rahel and Kumar, N Samba and Jathanna, Devcharan and Karanth, K Ullas} } @article {43844, title = {Store-Operated Ca Entry in Drosophila Primary Neuronal Cultures.}, journal = {Methods Mol Biol}, volume = {1843}, year = {2018}, month = {2018}, pages = {125-136}, abstract = {

Intracellular calcium signals in neurons frequently derive from the stimulation of G protein-coupled receptors (GPCR) by neurotransmitters, neuropeptides, and neurohormones. GPCR stimulation in neurons leads to generation of inositol 1,4,5-trisphosphate (IP), which in turn activates endoplasmic reticulum (ER)-localized IP receptors. The IP receptor\ (IPR) is a ligand-gated Ca channel, which releases Ca from ER stores. In Drosophila neurons it has been shown that depletion of ER Ca store is followed by store-operated Ca entry (SOCE) through STIM\ and Orai, the ER Ca sensor and the plasma membrane Ca channel respectively. The elucidation of this Ca signaling pathway in neurons has in part been possible\ due to the ease of genetic manipulation in Drosophila, which has allowed neuron-specific knockdown of various proteins of interest. This has been followed by standardization of conditions for culturing neurons from dissected brains of the relevant genotypes, such that they could be used for robust Ca measurements by imaging with standard Ca indicator dyes. Protocols for measurement of IP-mediated Ca release, passive depletion of ER Ca store, and SOCE in primary cultures of Drosophila neurons are described here.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-8704-7_11}, author = {Chakraborty, Sumita and Hasan, Gaiti} } @article {30082, title = {Structural basis for substrate discrimination by E. coli repair enzyme, AlkB}, journal = {RSC ADVANCES}, volume = {8}, year = {2018}, month = {2018}, pages = {1281-1291}, abstract = {

E. coli AlkB, a repair enzyme of the dioxygenase family, catalyses the removal of mutagenic methylated nucleotides from the genome. Known for substrate promiscuity, AlkB{\textquoteright}s catalytic mechanism and conformational changes accompanying substrate binding have been extensively dissected. However, the structural parameters of various substrates governing their recognition by AlkB still remain elusive. In this work, through solution-state vibrational spectra of methylated substrates bound to AlkB in combination with computational analysis, we show that the recognition specificity is dictated by the protonation states of the substrates. Specificity is conferred predominantly through hydrogen bonding and cation{\textendash}π interactions. Furthermore, we report on the interaction of AlkB with normal, unmodified nucleotides, wherein the presence of an exocyclic amino group serves as an essential criterion for the initial process of substrate recognition. Taken together, these results provide a rationale for structural determinants of substrate specificity as well as mode of lesion discrimination employed by AlkB.

}, doi = {10.1039/c7ra11333a}, author = {Jayanth, Namrata and Ogirala, Nirmala and Yadav, Anil and Puranik, Mrinalini} } @article {35145, title = {Structural mechanisms of oligomer and amyloid fibril formation by the prion protein.}, journal = {Chem Commun (Camb)}, year = {2018}, month = {2018 May 23}, abstract = {

Misfolding and aggregation of the prion protein is responsible for multiple neurodegenerative diseases. Works from several laboratories on folding of both the WT and multiple pathogenic mutant variants of the prion protein have identified several structurally dissimilar intermediates, which might be potential precursors to misfolding and aggregation. The misfolded aggregates themselves are morphologically distinct, critically dependent on the solution conditions under which they are prepared, but always β-sheet rich. Despite the lack of an atomic resolution structure of the infectious pathogenic agent in prion diseases, several low resolution models have identified the β-sheet rich core of the aggregates formed in vitro, to lie in the α2-α3 subdomain of the prion protein, albeit with local stabilities that vary with the type of aggregate. This feature article describes recent advances in the investigation of in vitro prion protein aggregation using multiple spectroscopic probes, with particular focus on (1) identifying aggregation-prone conformations of the monomeric protein, (2) conditions which trigger misfolding and oligomerization, (3) the mechanism of misfolding and aggregation, and (4) the structure of the misfolded intermediates and final aggregates.

}, issn = {1364-548X}, doi = {10.1039/c8cc03053g}, author = {Sengupta, Ishita and Udgaonkar, Jayant B} } @article {26286, title = {Structure and development of the subesophageal zone of the Drosophila brain. II. Sensory compartments.}, journal = {J Comp Neurol}, volume = {526}, year = {2018}, month = {2018 Jan 01}, pages = {33-58}, abstract = {

The subesophageal zone (SEZ) of the Drosophila brain processes mechanosensory and gustatory sensory input from sensilla located on the head, mouth cavity and trunk. Motor output from the SEZ directly controls the movements involved in feeding behavior. In an accompanying paper (Hartenstein et al., ), we analyzed the systems of fiber tracts and secondary lineages to establish reliable criteria for defining boundaries between the four neuromeres of the SEZ, as well as discrete longitudinal neuropil domains within each SEZ neuromere. Here we use this anatomical framework to systematically map the sensory projections entering the SEZ throughout development. Our findings show continuity between larval and adult sensory neuropils. Gustatory axons from internal and external taste sensilla of the larva and adult form two closely related sensory projections, (a) the anterior central sensory center located deep in the ventromedial neuropil of the tritocerebrum and mandibular neuromere, and (b) the anterior ventral sensory center (AVSC), occupying a superficial layer within the ventromedial tritocerebrum. Additional, presumed mechanosensory terminal axons entering via the labial nerve define the ventromedial sensory center (VMSC) in the maxilla and labium. Mechanosensory afferents of the massive array of chordotonal organs (Johnston{\textquoteright}s organ) of the adult antenna project into the centrolateral neuropil column of the anterior SEZ, creating the antenno-mechanosensory and motor center (AMMC). Dendritic projections of dye back-filled motor neurons extend throughout a ventral layer of the SEZ, overlapping widely with the AVSC and VMSC. Our findings elucidate fundamental structural aspects of the developing sensory systems in Drosophila.

}, issn = {1096-9861}, doi = {10.1002/cne.24316}, author = {Kendroud, Sarah and Bohra, Ali A and Kuert, Philipp A and Nguyen, Bao and Guillermin, Oriane and Sprecher, Simon G and Reichert, Heinrich and VijayRaghavan, Krishnaswamy and Hartenstein, Volker} } @article {36274, title = {Substituting space for time: Empirical evaluation of spatial replication as a surrogate for temporal replication in occupancy modelling }, journal = {JOURNAL OF APPLIED ECOLOGY }, volume = {55}, year = {2018}, month = {03/2018}, pages = {754-765}, doi = {10.1111/1365-2664.13005 }, author = {Srivathsa, A and Puri, M and Kumar, NS and Jathanna, D and Karanth, KU} } @article {46414, title = {Subunit exchange enhances information retention by CaMKII in dendritic spines.}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 Nov 12}, abstract = {

Molecular bistables are strong candidates for long-term information storage, for example, in synaptic plasticity. Calcium/calmodulin dependent protein Kinase II (CaMKII) is a highly expressed synaptic protein which has been proposed to form a molecular bistable switch capable of maintaining its state for years despite protein turnover and stochastic noise. It has recently been shown that CaMKII holoenzymes exchange subunits among themselves. Here we used computational methods to analyze the effect of subunit exchange on the CaMKII pathway in the presence of diffusion in two different micro-environments, the post synaptic density (PSD) and spine cytosol. We show that CaMKII exhibits multiple timescales of activity due to subunit exchange. Further, subunit exchange enhances information retention by CaMKII both by improving the stability of its switching in the PSD, and by slowing the decay of its activity in the spine cytosol. The existence of diverse timescales in the synapse has important theoretical implications for memory storage in networks.

}, issn = {2050-084X}, doi = {10.7554/eLife.41412}, author = {Singh, Dilawar and Bhalla, Upinder Singh} } @article {48887, title = {Sugar Intake Elicits Intelligent Searching Behavior in Flies and Honey Bees.}, journal = {Front Behav Neurosci}, volume = {12}, year = {2018}, month = {2018}, pages = {280}, abstract = {

We present a comparison of the sugar-elicited search behavior in and . In both species, intake of sugar-water elicits a complex of searching responses. The most obvious response was an increase in turning frequency. However, we also found that flies and honey bees returned to the location of the sugar drop. They even returned to the food location when we prevented them from using visual and chemosensory cues. Analyses of the recorded trajectories indicated that flies and bees use two mechanisms, a locomotor pattern involving an increased turning frequency and path integration to increase the probability to stay close or even return to the sugar drop location. However, evidence for the use of path integration in honey bees was less clear. In general, walking trajectories of honey bees showed a higher degree of curvature and were more spacious; two characters which likely masked evidence for the use of path integration in our experiments. Visual cues, i.e., a black dot, presented underneath the sugar drop made flies and honey bees stay closer to the starting point of the search. In honey bees, vertical black columns close to the sugar drop increased the probability to visit similar cues in the vicinity. An additional one trial learning experiment suggested that the intake of sugar-water likely has the potential to initiate an associative learning process. Together, our experiments indicate that the sugar-elicited local search is more complex than previously assumed. Most importantly, this local search behavior appeared to exhibit major behavioral capabilities of large-scale navigation. Thus, we propose that sugar-elicited search behavior has the potential to become a fruitful behavioral paradigm to identify neural and molecular mechanisms involved in general mechanisms of navigation.

}, issn = {1662-5153}, doi = {10.3389/fnbeh.2018.00280}, author = {Brockmann, Axel and Basu, Pallab and Shakeel, Manal and Murata, Satoshi and Murashima, Naomi and Boyapati, Ravi Kumar and Prabhu, Nikhil G and Herman, Jacob J and Tanimura, Teiichi} } @article {38424, title = {Switch-like PKA responses in the nucleus of striatal neurons.}, journal = {J Cell Sci}, year = {2018}, month = {2018 Jul 02}, abstract = {

Although it is known that Protein Kinase A (PKA) in the nucleus regulates gene expression, the specificities of nuclear PKA signaling remain poorly understood. Here, we combined computational modeling and live-cell imaging of PKA-dependent phosphorylation in mouse brain slices to investigate how transient dopamine signals are translated into nuclear PKA activity in cortical pyramidal neurons and striatal medium spiny neurons. We observed that the nuclear PKA signal in striatal neurons featured an ultrasensitive responsiveness, associated with fast, all or none responses, which is not consistent with the commonly accepted theory of a slow and passive diffusion of catalytic PKA in the nucleus. Our numerical model suggests that a positive feed-forward mechanism inhibiting nuclear phosphatase activity - possibly mediated by DARPP-32 - could be responsible for this non-linear pattern of nuclear PKA response, allowing for a better detection of the transient dopamine signals that are often associated with reward-mediated learning.

}, issn = {1477-9137}, doi = {10.1242/jcs.216556}, author = {Yapo, Cedric and Nair, Anu G and Hellgren Kotaleski, Jeanette and Vincent, Pierre and Castro, Liliana R V} } @article {43839, title = {Time-restricted foraging under natural light/dark condition shifts the molecular clock in the honey bee, Apis mellifera.}, journal = {Chronobiol Int}, year = {2018}, month = {2018 Sep 25}, pages = {1-12}, abstract = {

Honey bees have a remarkable sense of time and individual honey bee foragers are capable of adjusting their foraging activity with respect to the time of food availability. Although, there is compelling experimental evidence that foraging behavior is guided by the circadian clock, nothing is known about the underlying molecular mechanisms. Here we present for the first time a study that explores whether time-restricted foraging under natural light-dark (LD) condition affects the molecular clock in honey bees. Food was presented in an enclosed flight chamber (12\ m {\texttimes} 4\ m {\texttimes} 4\ m) either for 2\ hours in the morning or 2\ hours in the afternoon for several consecutive days and daily cycling of the two major clock genes, cryptochrome2 (cry2) and period (per), were analyzed for three different parts of the nervous system involved in feeding-related behaviors: brain, subesophageal ganglion (SEG), and the antennae with olfactory sensory neurons. We found that morning and afternoon trained foragers showed significant phase differences in the cycling of both clock genes in all three tissues. In addition, the phase differences were more pronounced when the feeder was scented with the common plant odor, linalool. Together our findings suggest that foraging time may function as a Zeitgeber that might have the capability to modulate the light entrained molecular clock.

}, issn = {1525-6073}, doi = {10.1080/07420528.2018.1509867}, author = {Jain, Rikesh and Brockmann, Axel} } @article {39418, title = {The transcription factor Lef1 switches partners from β-catenin to Smad3 during muscle stem cell quiescence.}, journal = {Sci Signal}, volume = {11}, year = {2018}, month = {2018 Jul 24}, abstract = {

Skeletal muscle stem cells (MuSCs), also known as satellite cells, persist in adult mammals by entering a state of quiescence (G) during the early postnatal period. Quiescence is reversed during damage-induced regeneration and re-established after regeneration. Entry of cultured myoblasts into G is associated with a specific, reversible induction of Wnt target genes, thus implicating members of the Tcf and Lef1 (Tcf/Lef) transcription factor family, which mediate transcriptional responses to Wnt signaling, in the initiation of quiescence. We found that the canonical Wnt effector β-catenin, which cooperates with Tcf/Lef, was dispensable for myoblasts to enter quiescence. Using pharmacological and genetic approaches in cultured C2C12 myoblasts and in MuSCs, we demonstrated that Tcf/Lef activity during quiescence depended not on β-catenin but on the transforming growth factor-β (TGF-β) effector and transcriptional coactivator Smad3, which colocalized with Lef1 at canonical Wnt-responsive elements and directly interacted with Lef1 specifically in G Depletion of Smad3, but not β-catenin, reduced Lef1 occupancy at target promoters, Tcf/Lef target gene expression, and self-renewal of myoblasts. In vivo, MuSCs underwent a switch from β-catenin-Lef1 to Smad3-Lef1 interactions during the postnatal switch from proliferation to quiescence, with β-catenin-Lef1 interactions recurring during damage-induced reactivation. Our findings suggest that the interplay of Wnt-Tcf/Lef and TGF-β-Smad3 signaling activates canonical Wnt target promoters in a manner that depends on β-catenin during myoblast proliferation but is independent of β-catenin during MuSC quiescence.

}, issn = {1937-9145}, doi = {10.1126/scisignal.aan3000}, author = {Aloysius, Ajoy and DasGupta, Ramanuj and Dhawan, Jyotsna} } @article {22813, title = {Transcriptional profiling of human neural precursors post alcohol exposure reveals impaired neurogenesis via dysregulation of ERK signaling and miR-145.}, journal = {J Neurochem}, volume = {146}, year = {2018}, month = {2018}, pages = {47-62}, abstract = {

Gestational alcohol exposure causes a range of neuropsychological disorders by modulating neurodevelopmental genes and proteins. The extent of damage depends on the stage of the embryo, as well as dosage, duration, and frequency of exposure. Here, we investigated the neurotoxic effects of alcohol using Human Embryonic Stem Cells (hESC). Multiple read-outs were engaged to assess the proliferation and differentiation capacity of neural precursor cells (NPC) upon exposure to 100 mM ethanol for 48 hrs corresponding to the blood alcohol levels for binge drinkers. Whole genome analysis revealed a spatiotemporal dysregulation of neuronal and glial specific gene expression that play critical roles in Central Nervous System (CNS) development. Alterations observed in the transcriptome may be attributed to epigenetic constitution witnessed by differential histone H3 Lys-4/Lys-27 modifications and acetylation status. In-depth mRNA and protein expression studies revealed abrogated ERK signaling in alcohol- treated cells. Consistent with this finding, Ingenuity Pathway Analysis (IPA) and microRNA profiling demonstrated upregulation of miR-145 by targeting the neural specifier Sox-2. We also show that the neurite branching complexity of TUJ1+ neurons was greatly reduced in response to alcohol. Lastly, in vivo studies using zebrafish embryos reconfirmed the in vitro findings. Employing molecular endpoints in a human model, this report indicates for the first time that acute alcohol exposure could lead to impaired brain development via perturbation of ERK pathway and miR-145. However, it still needs to be addressed whether these modulations sustain throughout development, compromising the ability of the individual during adulthood and aging. This article is protected by copyright. All rights reserved.

}, issn = {1471-4159}, doi = {10.1111/jnc.14155}, author = {Louis, Lithin K and Gopurappilly, Renjitha and Surendran, Harshini and Dutta, Sunit and Pal, Rajarshi} } @article {29619, title = {Translational selection for speed is not sufficient to explain variation in bacterial codon usage bias.}, journal = {Genome Biol Evol}, year = {2018}, month = {2018 Jan 29}, abstract = {

Increasing growth rate across bacteria strengthens selection for faster translation, concomitantly increasing the total number of tRNA genes and codon usage bias (CUB: enrichment of specific synonymous codons in highly expressed genes). Typically, enriched codons are translated by tRNAs with higher gene copy numbers (GCN). A model of tRNA-CUB coevolution based on fast growth associated selection on translational speed recapitulates these patterns. A key untested implication of the coevolution model is that translational selection should favor higher tRNA GCN for more frequently used amino acids, potentially weakening the effect of growth associated selection on CUB. Surprisingly, we find that CUB saturates with increasing growth rate across γ-proteobacteria, even as the number of tRNA genes continues to increase. As predicted, amino acid specific tRNA GCN is positively correlated with the usage of corresponding amino acids, but there is no correlation between growth rate associated changes in CUB and amino acid usage. Instead, we find that some amino acids - Cysteine and those in the NNA/G codon family - show weak CUB that does not increase with growth rate, despite large variation in the corresponding tRNA GCN. We suggest that amino acid specific variation in CUB is not explained by tRNA GCN because GCN does not influence the difference between translation times of synonymous codons as expected. Thus, selection on translational speed alone cannot fully explain quantitative variation in overall or amino acid specific CUB, suggesting a significant role for other functional constraints and amino acid specific codon features.

}, issn = {1759-6653}, doi = {10.1093/gbe/evy018}, author = {Mahajan, Saurabh and Agashe, Deepa} } @article {29827, title = {Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement.}, journal = {Cell}, volume = {172}, year = {2018}, month = {2018 Jan 11}, pages = {305-317.e10}, abstract = {

Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins ("pickets") that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in\ phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket. CD44 tethers reversibly to formin-induced actin filaments, curtailing receptor diffusion. Such linear filaments predominate in the trailing end of polarized macrophages, where receptor mobility was minimal. Conversely, receptors were most mobile at the leading edge, where Arp2/3-driven actin branching predominates. CD44 binds hyaluronan, anchoring a pericellular coat that also limits receptor displacement and obstructs access to phagocytic targets. Force must be applied to traverse the pericellular barrier, enabling receptors to engage their targets.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2017.12.023}, author = {Freeman, Spencer A and Vega, Anthony and Riedl, Magdalena and Collins, Richard F and Ostrowski, Phillip P and Woods, Elliot C and Bertozzi, Carolyn R and Tammi, Markku I and Lidke, Diane S and Johnson, Pauline and Mayor, Satyajit and Jaqaman, Khuloud and Grinstein, Sergio} } @article {36266, title = {Two new species of bent toed geckos, Cyrtodactylus Gray, 1827 (Squamata: Gekkonidae) from Northeast India with comments on name-bearing types from the region }, journal = {ZOOTAXA}, volume = {4420 }, year = {2018}, month = {05/2018}, pages = {334-356}, abstract = {

Two new species of the genus Cyrtodactylus are described based on collections from Northeast India, and descriptions and diagnoses of previously described species and synonyms from the region are provided. One of the new species from lowland habitats in Tripura is medium sized, with a continuous series of precloacal pores, and is allied to C. ayeyarwadyensis from Myanmar; while the other new species from West Bengal is smaller, with both femoral and precloacal pores, and is related to C. gubernatoris from West Bengal and Sikkim. We designate a lectotype for Cyrtodactylus khasiensis and recognize the C. khasiensis synonym Gymnodactylus himalayicus as a valid species of Cyrtodactylus based on morphological evidence, and suggest the recognition of the last remaining subspecies of C. khasiensis, C. k. cayuensis, as a valid species based on geography and morphology. The stabilization of the taxa Cyrtodactylus khasiensis and C. gubernatoris with a limited subset of characters and specific distributional data, as well as the elevation of Cyrtodactylus himalayicus comb. nov. from synonymy, will allow the descriptions of many more Cyrtodactylus species from the region.

}, doi = {10.11646/zootaxa.4420.3.2 }, author = {Agarwal, I and Mahony, S and Giri, VB and Chaitanya, R and Bauer, AM} } @article {36664, title = {Two new species of the Ophisops microlepis (Squamata: Lacertidae) complex from northwestern India with a key to Indian Ophisops }, journal = {JOURNAL OF NATURAL HISTORY }, volume = {52}, year = {2018}, month = {2018}, pages = {819-847 }, doi = {10.1080/00222933.2018.1436203 }, author = {Agarwal, I and Khandekar, A and Ramakrishnan, U and Vyas, R and Giri, VB} } @article {36659, title = {Ubiquitous abundance distribution of non-dominant plankton across the global ocean.}, journal = {Nat Ecol Evol}, year = {2018}, month = {2018 Jun 18}, abstract = {

Marine plankton populate 70\% of Earth{\textquoteright}s surface, providing the energy that fuels ocean food webs and contributing to global biogeochemical cycles. Plankton communities are extremely diverse and geographically variable, and are overwhelmingly composed of low-abundance species. The role of this rare biosphere and its ecological underpinnings are however still unclear. Here, we analyse the extensive dataset generated by the Tara Oceans expedition for marine microbial eukaryotes (protists) and use an adaptive algorithm to explore how metabarcoding-based abundance distributions vary across plankton communities in the global ocean. We show that the decay in abundance of non-dominant operational taxonomic units, which comprise over 99\% of local richness, is commonly governed by a power-law. Despite the high spatial turnover in species composition, the power-law exponent varies by less than 10\% across locations and shows no biogeographical signature, but is weakly modulated by cell size. Such striking regularity suggests that the assembly of plankton communities in the dynamic and highly variable ocean environment is governed by large-scale ubiquitous processes. Understanding their origin and impact on plankton ecology will be important for evaluating the resilience of marine biodiversity in a changing ocean.

}, issn = {2397-334X}, doi = {10.1038/s41559-018-0587-2}, author = {Ser-Giacomi, Enrico and Zinger, Lucie and Malviya, Shruti and de Vargas, Colomban and Karsenti, Eric and Bowler, Chris and De Monte, Silvia} } @article {45446, title = {UNC-16/JIP3 and UNC-76/FEZ1 limit the density of mitochondria in C. elegans neurons by maintaining the balance of anterograde and retrograde mitochondrial transport.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 Jun 12}, pages = {8938}, abstract = {

We investigate the role of axonal transport in regulating neuronal mitochondrial density. We show that the density of mitochondria in the touch receptor neuron (TRN) of adult Caenorhabditis elegans is constant. Mitochondrial density and transport are controlled both by the Kinesin heavy chain and the Dynein-Dynactin complex. However, unlike in other models, the presence of mitochondria in C. elegans TRNs depends on a Kinesin light chain as well. Mutants in the three C. elegans miro genes do not alter mitochondrial density in the TRNs. Mutants in the Kinesin-1 associated proteins, UNC-16/JIP3 and UNC-76/FEZ1, show increased mitochondrial density and also have elevated levels of both the Kinesin Heavy and Light Chains in neurons. Genetic analyses suggest that, the increased mitochondrial density at the distal end of the neuronal process in unc-16 and unc-76 depends partly on Dynein. We observe a net anterograde bias in the ratio of anterograde to retrograde mitochondrial flux in the neuronal processes of unc-16 and unc-76, likely due to both increased Kinesin-1 and decreased Dynein in the neuronal processes. Our study shows that UNC-16 and UNC-76 indirectly limit mitochondrial density in the neuronal process by maintaining a balance in anterograde and retrograde mitochondrial axonal transport.

}, issn = {2045-2322}, doi = {10.1038/s41598-018-27211-9}, author = {Sure, Guruprasada Reddy and Chatterjee, Anusheela and Mishra, Nikhil and Sabharwal, Vidur and Devireddy, Swathi and Awasthi, Anjali and Mohan, Swetha and Koushika, Sandhya P} } @article {32028, title = {Using stochastic cell division and death to probe minimal units of cellular replication}, journal = {New Journal of Physics}, volume = {20}, year = {2018}, month = {03/2018}, abstract = {

The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in Escherichia coli populations treated with a ribosome-targeting antibiotic. We find that the growth exponent from macroscopic cell growth or decay measurements can be represented as the difference of microscopic first-order cell division and death rates. The boundary between cell growth and decay, at which the number of live cells remains constant over time, occurs at the minimal inhibitory concentration (MIC) of the antibiotic. This state appears macroscopically static but is microscopically dynamic: division and death rates exactly cancel at MIC but each is remarkably high, reaching 60\% of the antibiotic-free division rate. A stochastic model of cells as collections of minimal replicating units we term {\textquoteright}widgets{\textquoteright} reproduces both steady-state and transient features of our experiments. Sub-cellular fluctuations of widget numbers stochastically drive each new daughter cell to one of two alternate fates, division or death. First-order division or death rates emerge as eigenvalues of a stationary Markov process, and can be expressed in terms of the widget{\textquoteright}s molecular properties. High division and death rates at MIC arise due to low mean and high relative fluctuations of widget number. Isolating cells at the threshold of irreversible death might allow molecular characterization of this minimal replication unit.

}, doi = {10.1088/1367-2630/aab197}, author = {Chib, Savita and Das, Suman and Venkatesan, S and Seshasayee, Aswin S N and Thattai, Mukund} } @article {53990, title = {Using stochastic cell division and death to probe minimal units of cellular replication.}, journal = {New J Phys}, volume = {20}, year = {2018}, month = {2018 Mar}, pages = {035004}, abstract = {

The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in populations treated with a ribosome-targeting antibiotic. We find that the growth exponent from macroscopic cell growth or decay measurements can be represented as the difference of microscopic first-order cell division and death rates. The boundary between cell growth and decay, at which the number of live cells remains constant over time, occurs at the minimal inhibitory concentration (MIC) of the antibiotic. This state appears macroscopically static but is microscopically dynamic: division and death rates exactly cancel at MIC but each is remarkably high, reaching 60\% of the antibiotic-free division rate. A stochastic model of cells as collections of minimal replicating units we term {\textquoteright}widgets{\textquoteright} reproduces both steady-state and transient features of our experiments. Sub-cellular fluctuations of widget numbers stochastically drive each new daughter cell to one of two alternate fates, division or death. First-order division or death rates emerge as eigenvalues of a stationary Markov process, and can be expressed in terms of the widget{\textquoteright}s molecular properties. High division and death rates at MIC arise due to low mean and high relative fluctuations of widget number. Isolating cells at the threshold of irreversible death might allow molecular characterization of this minimal replication unit.

}, issn = {1367-2630}, doi = {10.1088/1367-2630/aab197}, author = {Chib, Savita and Das, Suman and Venkatesan, Soumya and Seshasayee, Aswin Sai Narain and Thattai, Mukund} } @article {36660, title = {ViXeN: An open-source package for managing multimedia data}, journal = {METHODS IN ECOLOGY AND EVOLUTION }, volume = {9}, year = {2018}, month = {03/2018}, pages = {785-792 }, doi = {10.1111/2041-210X.12892 }, author = {Ramachandran, P and Devarajan, K} } @article {29629, title = {Wnt and Hedgehog: Secretion of Lipid-Modified Morphogens.}, journal = {Trends Cell Biol}, volume = {28}, year = {2018}, month = {2018 Feb}, pages = {157-170}, abstract = {

Morphogens are signaling molecules produced by a localized source, specifying cell fate in a graded manner. The source secretes morphogens into the extracellular milieu to activate various target genes in an autocrine or paracrine manner. Here we describe various secreted forms of two canonical morphogens, the lipid-anchored Hedgehog (Hh) and Wnts, indicating the involvement of multiple carriers in the transport of these morphogens. These different extracellular secreted forms are likely to have distinct functions. Here we evaluate newly identified mechanisms that morphogens use to traverse the required distance to activate discrete paracrine signaling.

}, issn = {1879-3088}, doi = {10.1016/j.tcb.2017.10.003}, author = {Parchure, Anup and Vyas, Neha and Mayor, Satyajit} } @article {35144, title = {Wobbling forth and drifting back: The evolutionary history and impact of bacterial tRNA modifications.}, journal = {Mol Biol Evol}, year = {2018}, month = {2018 May 28}, abstract = {

Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific ("target") tRNAs to recognize multiple codons and cover for other ("non-target") tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in non-target tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.

}, issn = {1537-1719}, doi = {10.1093/molbev/msy110}, author = {Diwan, Gaurav D and Agashe, Deepa} } @article {26660, title = {On the absence of Ichthyophis sikkimensis Taylor, 1960 (Amphibia: Gymnophiona: Ichthyophiidae) in the Western Ghats of peninsular India}, journal = {Herpetological Journal}, volume = {27}, year = {2017}, month = {04/2017}, pages = {181-187}, abstract = {

We examined two specimens of short-tailed, unstriped Ichthyophis Fitzinger, 1843 collected in 1949 from the Anamalai Hills of the Western Ghats of peninsular India. One of these specimens was identified previously as the peninsular Indian I. subterrestris Taylor, 1960, the other as I. sikkimensis Taylor, 1960, a species known otherwise only from Nepal and the Indian states of Sikkim and West Bengal, approximately 2,200 km to the northeast. We find that the two specimens in question are conspecific, that both have been misidentified and that the pair together probably belong to an undescribed species. Our conclusion that I. sikkimensis does not occur in peninsular India removes a major biogeographic anomaly.

}, author = {Gower, DJ and Kamei, RG and Giri, Varad and Wilkinson, Mark} } @article {25251, title = {Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {2017 Oct 03}, pages = {10648-10653}, abstract = {

Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven "retrograde flow" of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.

}, issn = {1091-6490}, doi = {10.1073/pnas.1701136114}, author = {Swaminathan, Vinay and Kalappurakkal, Joseph Mathew and Mehta, Shalin B and Nordenfelt, Pontus and Moore, Travis I and Koga, Nobuyasu and Baker, David A and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Springer, Timothy A and Waterman, Clare M} } @article {18678, title = {Activation of the same mGluR5 receptors in the amygdala causes divergent effects on specific versus indiscriminate fear.}, journal = {Elife}, volume = {6}, year = {2017}, month = {2017 May 30}, abstract = {

Although mGluR5-antagonists prevent fear and anxiety, little is known about how the same receptor in the amygdala gives rise to both. Combining in vitro and in vivo activation of mGluR5 in rats, we identify specific changes in intrinsic excitability and synaptic plasticity in basolateral amygdala neurons that give rise to temporally distinct and mutually exclusive effects on fear-related behaviors. The immediate impact of mGluR5 activation is to produce anxiety manifested as indiscriminate fear of both tone and context. Surprisingly, this state does not interfere with the proper encoding of tone-shock associations that eventually lead to enhanced cue-specific fear. These results provide a new framework for dissecting the functional impact of amygdalar mGluR-plasticity on fear versus anxiety in health and disease.

}, issn = {2050-084X}, doi = {10.7554/eLife.25665}, author = {Rahman, Mohammed Mostafizur and Kedia, Sonal and Fernandes, Giselle and Chattarji, Sumantra} } @article {25253, title = {Actomyosin pulsation and flows in an active elastomer with turnover and network remodeling.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Oct 24}, pages = {1121}, abstract = {

Tissue remodeling requires cell shape changes associated with pulsation and flow of the actomyosin cytoskeleton. Here we describe the hydrodynamics of actomyosin as a confined active elastomer with turnover of its components. Our treatment is adapted to describe the diversity of contractile dynamical regimes observed in vivo. When myosin-induced contractile stresses are low, the deformations of the active elastomer are affine and exhibit spontaneous oscillations, propagating waves, contractile collapse and spatiotemporal chaos. We study the nucleation, growth and coalescence of actomyosin-dense regions that, beyond a threshold, spontaneously move as a spatially localized traveling front. Large myosin-induced contractile stresses lead to nonaffine deformations due to enhanced actin and crosslinker turnover. This results in a transient actin network that is constantly remodeling and naturally accommodates intranetwork flows of the actomyosin-dense regions. We verify many predictions of our study in Drosophila embryonic epithelial cells undergoing neighbor exchange during germband extension.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-01130-1}, author = {Banerjee, Deb Sankar and Munjal, Akankshi and Lecuit, Thomas and Rao, Madan} } @article {19528, title = {Adaptive Genetic Exchange: A Tangled History of Admixture and Evolutionary Innovation.}, journal = {Trends Ecol Evol}, year = {2017}, month = {2017 Jun 20}, abstract = {

Genetic exchange between divergent evolutionary lineages, from introgressive hybridization between locally adapted populations to insertion of retroviral sequences into eukaryotic genomes, has now been documented. The detection of frequent divergence-with-gene-flow contrasts the neo-Darwinian paradigm of largely allopatric diversification. Nevertheless, of even greater significance is the growing wealth of data suggesting that the recipients of the transferred genomic material gain adaptive phenotypes from the donor lineages. This adaptive enrichment is reflected by changes in pathogenicity in viruses and bacteria, the transformation of ecological amplitude in eukaryotes, and adaptive radiations in extremely diverse lineages. Although genetic exchange may produce maladaptive consequences, most of the recently reported examples suggest increases in fitness, and many such adaptive trait transfers have been identified in our own species.

}, issn = {1872-8383}, doi = {10.1016/j.tree.2017.05.007}, author = {Arnold, Michael L and Kunte, Krushnamegh} } @article {14059, title = {Alternative reproductive tactics and inverse size-assortment in a high-density fish spawning aggregation.}, journal = {BMC Ecol}, volume = {17}, year = {2017}, month = {2017 Feb 28}, pages = {10}, abstract = {

BACKGROUND: At high densities, terrestrial and marine species often employ alternate reproductive tactics (ARTs) to maximize reproductive benefits. We describe ARTs in a high-density and unfished spawning aggregation of the squaretail grouper (Plectropomus areolatus) in Lakshadweep, India.

RESULTS: As previously reported for this species, territorial males engage in pair-courtship, which is associated with a pair-spawning tactic. Here, we document a previously unreported school-courtship tactic; where territorial males court multiple females in mid-water schools, which appears to culminate in a unique {\textquoteright}school-spawning{\textquoteright} tactic. Courtship tactics were conditional on body size, local mate density and habitat, likely associated with changing trade-offs between potential mating opportunities and intra-sexual competition. Counter-intuitively, the aggregation showed a habitat-specific inverse size-assortment: large males courted small females on the reef slope while small males courted equal-sized or larger females on the shelf. These patterns remained stable across two years of observation at high, unfished densities.

CONCLUSIONS: These unique density-dependent behaviours may disappear from this aggregation as overall densities decline due to increasing commercial fishing pressure, with potentially large consequences for demographics and fitness.

}, issn = {1472-6785}, doi = {10.1186/s12898-017-0120-5}, author = {Karkarey, Rucha and Zambre, Amod and Isvaran, Kavita and Arthur, Rohan} } @article {20316, title = {Amino-acid composition after loop deletion drives domain swapping.}, journal = {Protein Sci}, volume = {26}, year = {2017}, month = {10/2017}, chapter = {1994}, abstract = {

Rational engineering of a protein to enable domain swapping requires an understanding of the sequence, structural and energetic factors that favor the domain-swapped oligomer over the monomer. While it is known that the deletion of loops between β-strands can promote domain swapping, the spliced sequence at the position of the loop deletion is thought to have a minimal role to play in such domain swapping. Here, two loop-deletion mutants of the non-domain-swapping protein monellin, frame-shifted by a single residue, were designed. Although the spliced sequence in the two mutants differed by only one residue at the site of the deletion, only one of them (YEIKG) promoted domain swapping. The mutant containing the spliced sequence YENKG was entirely monomeric. This new understanding that the domain swapping propensity after loop deletion may depend critically on the chemical composition of the shortened loop will facilitate the rational design of domain swapping. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.3237}, author = {Nandwani, Neha and Surana, Parag and Udgaonkar, Jayant B and Das, Ranabir and Gosavi, Shachi} } @article {7595, title = {Analysis of Residue Conformations in Peptides in CSD and Protein-peptide Structural Complexes.}, journal = {Chem Biol Drug Des}, year = {2017}, month = {03/2017}, abstract = {

A comprehensive statistical analysis of the geometric parameters of peptide chains in a reduced dataset of protein-peptide complexes in PDB is presented. The angular variables describing the backbone conformations of amino acid residues in peptide chains shed insights into the conformational preferences of peptide residues interacting with protein partners. Non-parametric statistical approaches are employed to evaluate the interrelationships and associations in structural variables. Grouping of residues based on their structure into chemical classes reveals characteristic trends in parameter relationships. A comparison of canonical amino acid residues in free peptide structures in Cambridge Structural Database (CSD) with identical residues in PDB complexes, suggests that the information can be integrated from both the structural repositories enabling efficient and accurate modelling of biologically active peptides. This article is protected by copyright. All rights reserved.

}, issn = {1747-0285}, doi = {10.1111/cbdd.12862}, author = {Raghavender, Upadhyayula Surya} } @inbook {16850, title = {Artificial Induction and Maintenance of Epigenetic Variations in Plants}, booktitle = {Plant Gene Silencing: Mechanisms and Applications}, year = {2017}, pages = {59-75}, publisher = {CAB International}, organization = {CAB International}, chapter = {3}, isbn = {9781780647678}, author = {Das, Soumita and Singh, Rahul Raj and Shivaprasad, P V} } @article {157120, title = {Artificial induction and maintenance of epigenetic variations in plants.}, year = {2017}, abstract = {

Some of the studies initiated a decade ago to understand the behaviour of transgenes have provided the first clear evidence for transgene-mediated induction and subsequent inheritance of epigenetic marks in plants. Now there is enough proof to show that it is possible to induce methylation of DNA and histones and also to maintain them during subsequent generations without the need for the inducer. This chapter brings together recent advances in such artificial induction and suggests ways forward to make this technology an equivalent, if not better, strategy than genetic modification, which is clouded with never-ending controversies.

}, isbn = {ISBN (ePDF): 978-1-78064-768-5 ISBN (ePub): 978-1-78064-769-2 ISBN (Hardback): 978-1-78064-767-8}, url = {https://www.cabidigitallibrary.org/doi/10.1079/9781780647678.0059}, author = {Soumita Das Soumita Das and R. R. Singh and P V Shivaprasad} } @article {12890, title = {Back from the dead! Resurrection and revalidation of the Indian endemic snake genus Wallophis Werner, 1929 (Squamata: Colubridae) insights from molecular data.}, journal = {Mitochondrial DNA A DNA Mapp Seq Anal}, year = {2017}, month = {2017 Jan 27}, pages = {1-7}, abstract = {

The monotypic colubrid snake genus Wallophis is revalidated and rediagnosed. Partial sequence for nuclear gene Oocyte maturation factor Mos (c-mos), mitochondrial Nicotinamide adenine dinucleotide dehydrogenase subunit 4 (ND4) and cytochrome b (cyt b) were used to assess phylogenetic relationship. Wallophis brachyura type species for the genus was found to be a member of the Western Palearctic clade of Colubrinae and is recovered as a sister taxa to Wallaceophis gujaratensis. Wallophis differs from Wallaceophis in an uncorrected pairwise p-distance of 17\% for mitochondrial ND4 gene. Wallaceophis gujaratensis was described in three different spellings in the literature hence we here propose Wallaceophis gujaratensis as the correct spelling for the species based on provisions in the article 24.2.3. of the International Code for Zoological Nomenclature.

}, issn = {2470-1408}, doi = {10.1080/24701394.2016.1278536}, author = {Mirza, Zeeshan A and Patel, Harshil} } @article {26583, title = {Bats in the Ghats: Agricultural intensification reduces functional diversity and increases trait filtering in a biodiversity hotspot in India}, journal = {Biological Conservation}, volume = {210}, year = {2017}, month = {06/2017}, pages = {48-55}, abstract = {

The responses of bats to land-use change have been extensively studied in temperate zones and the neotropics, but little is known from the palaeotropics. Effective conservation in heavily-populated palaeotropical hotspots requires a better understanding of which bats can and cannot survive in human-modified landscapes. We used catching and acoustic transects to examine bat assemblages in the Western Ghats of India, and identify the species most sensitive to agricultural change. We quantified functional diversity and trait filtering of assemblages in forest fragments, tea and coffee plantations, and along rivers in tea plantations with and without forested corridors, compared to protected forests.

}, doi = {10.1016/j.biocon.2017.03.026}, author = {Claire F.R. Wordley and Sankaran, Mahesh and Divya Mudappa and Altringham, John D.} } @article {26656, title = {Bayesian Methods for Estimating Animal Abundance at Large Spatial Scales Using Data from Multiple Sources}, journal = {Journal of Agricultural, Biological and Environmental Statistics}, volume = {22}, year = {2017}, month = {06/2017}, pages = {111{\textendash}139}, abstract = {

Estimating animal distributions and abundances over large regions is of primary interest in ecology and conservation. Specifically, integrating data from reliable but expensive surveys conducted at smaller scales with cost-effective but less reliable data generated from surveys at wider scales remains a central challenge in statistical ecology. In this study, we use a Bayesian smoothing technique based on a conditionally autoregressive (CAR) prior distribution and Bayesian regression to address this problem. We illustrate the utility of our proposed methodology by integrating (i) abundance estimates of tigers in wildlife reserves from intensive photographic capture{\textendash}recapture methods, and (ii) estimates of tiger habitat occupancy from indirect sign surveys, conducted over a wider region. We also investigate whether the random effects which represent the spatial association due to the CAR structure have any confounding effect on the fixed effects of the regression coefficients.

}, author = {Dey, S and Delampady, M and Parameshwaran, Ravishankar and Samba Kumar, N and Srivathsa, Arjun and Karanth, Ullas} } @article {12204, title = {Big concerns with small projects: Evaluating the socio-ecological impacts of small hydropower projects in India.}, journal = {Ambio}, year = {2017}, month = {2017 Jan 10}, abstract = {

Although Small Hydropower Projects (SHPs) are encouraged as sources of clean and green energy, there is a paucity of research examining their socio-ecological impacts. We assessed the perceived socio-ecological impacts of 4 SHPs within the Western Ghats in India by conducting semi-structured interviews with local respondents. Primary interview data were sequentially validated with secondary data, and respondent perceptions were subsequently compared against the expected baseline of assured impacts. We evaluated the level of awareness about SHPs, their perceived socio-economic impacts, influence on resource access and impacts on human-elephant interactions. The general level of awareness about SHPs was low, and assurances of local electricity and employment generation remained largely unfulfilled. Additionally most respondents faced numerous unanticipated adverse impacts. We found a strong relationship between SHP construction and increasing levels of human-elephant conflict. Based on the disparity between assured and actual social impacts, we suggest that policies regarding SHPs be suitably revised.

}, issn = {1654-7209}, doi = {10.1007/s13280-016-0855-9}, author = {Jumani, Suman and Rao, Shishir and Machado, Siddarth and Prakash, Anup} } @article {22812, title = {Bioinformatics comparisons of RNA-binding proteins of pathogenic and non-pathogenic Escherichia coli strains reveal novel virulence factors.}, journal = {BMC Genomics}, volume = {18}, year = {2017}, month = {2017 Aug 24}, pages = {658}, abstract = {

BACKGROUND: Pathogenic bacteria have evolved various strategies to counteract host defences. They are also exposed to environments that are undergoing constant changes. Hence, in order to survive, bacteria must adapt themselves to the changing environmental conditions by performing regulations at the transcriptional and/or post-transcriptional levels. Roles of RNA-binding proteins (RBPs) as virulence factors have been very well studied. Here, we have used a sequence search-based method to compare and contrast the proteomes of 16 pathogenic and three non-pathogenic E. coli strains as well as to obtain a global picture of the RBP landscape (RBPome) in E. coli.

RESULTS: Our results show that there are no significant differences in the percentage of RBPs encoded by the pathogenic and the non-pathogenic E. coli strains. The differences in the types of Pfam domains as well as Pfam RNA-binding domains, encoded by these two classes of E. coli strains, are also insignificant. The complete and distinct RBPome of E. coli has been established by studying all known E. coli strains till date. We have also identified RBPs that are exclusive to pathogenic strains, and most of them can be exploited as drug targets since they appear to be non-homologous to their human host proteins. Many of these pathogen-specific proteins were uncharacterised and their identities could be resolved on the basis of sequence homology searches with known proteins. Detailed structural modelling, molecular dynamics simulations and sequence comparisons have been pursued for selected examples to understand differences in stability and RNA-binding.

CONCLUSIONS: The approach used in this paper to cross-compare proteomes of pathogenic and non-pathogenic strains may also be extended to other bacterial or even eukaryotic proteomes to understand interesting differences in their RBPomes. The pathogen-specific RBPs reported in this study, may also be taken up further for clinical trials and/or experimental validations.

}, issn = {1471-2164}, doi = {10.1186/s12864-017-4045-3}, author = {Ghosh, Pritha and Sowdhamini, Ramanathan} } @article {28254, title = {Cauline domatia of the ant-plant Humboldtia brunonis (Fabaceae)}, journal = {FLORA}, volume = {236-237}, year = {2017}, month = {11/2017}, chapter = {58-66}, abstract = {

We examined the morphology of the cauline domatia of the semi-myrmecophyte Humboldtia brunonis at different stages of ontogeny. We observed that the hollow chamber in H. brunonis is spontaneously formed by the plant, and suggest this to be a collective effect of both schizogeny and lysogeny, following acropetal lignification of the pith cells as the domatium internode swells up. Unlike some other cauline domatia, there is a self-opening slit that provides access to the domatium chamber. We investigated the micro-structure of the inner wall of the domatia using scanning electron microscopy, and observed that cells that form the inner lining of the domatia cavity have canaliculated, lignified sclerenchyma with numerous plasmodesmata, as reported for the true myrmecophyte Leonardoxa africana, which could explain the observed nutrient flux from domatia-dwelling invertebrates into the host plant. We also observed fungal mycelia in ant-occupied domatia, though the role of fungi in this ant-plant system awaits further investigation.

}, doi = {10.1016/j.flora.2017.09.005}, author = {Chanam, Joyshree and Borges, Renee M} } @article {25262, title = {Changing shape and shaping change: Inducing the inner ear.}, journal = {Semin Cell Dev Biol}, volume = {65}, year = {2017}, month = {2017 May}, pages = {39-46}, abstract = {

The inner ear arises from non-neural ectoderm as a result of instructions sent by surrounding tissues. These interactions progressively restrict the potential of the ectoderm, resulting in the formation of the otic placode, a disk of thickened ectoderm that will give rise to all of the inner ear derivatives and its neurons. While otic placode is a surface structure, the inner ear is internalised, embedded within the cranial mesenchyme. Here, the cellular and molecular interactions that restrict the lineage of non-neural ectoderm in its transition to otic placode are reviewed, and how these interactions impinge on the coordination of otic placodal cell shape that drive the dramatic morphogenesis of the placode, as it becomes the otocyst.

}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2016.10.006}, author = {Ladher, Raj K} } @article {26283, title = {Characterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Nov 15}, pages = {15600}, abstract = {

The conformational landscapes of p53 peptide variants\ and phage derived peptide (12/1) variants, all known to bind to MDM2, are studied using hamiltonian replica exchange molecular dynamics simulations. Complementing earlier observations, the current study suggests that the p53 peptides largely follow the {\textquoteright}conformational selection{\textquoteright} paradigm in their recognition of and complexation by MDM2 while the 12/1 peptides likely undergo some element of conformational selection but are mostly driven by {\textquoteright}binding induced folding{\textquoteright}. This hypothesis is further supported by pulling simulations that pull the peptides away from their bound states with MDM2. This data extends the earlier mechanisms proposed to rationalize the entropically driven binding of the p53 set and the enthalpically driven binding of the 12/1 set. Using our hypothesis, we suggest mutations to the 12/1 peptide that increase its helicity in simulations and may, in turn, shift the binding towards conformational selection. In summary, understanding the conformational landscapes of the MDM2-binding peptides may suggest new peptide designs with bespoke binding mechanisms.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-15930-4}, author = {Yadahalli, Shilpa and Li, Jianguo and Lane, David P and Gosavi, Shachi and Verma, Chandra S} } @article {22020, title = {Chemical Denaturants Smoothen Ruggedness on the Free Energy Landscape of Protein Folding.}, journal = {Biochemistry}, volume = {56}, year = {2017}, month = {2017 Aug 08}, pages = {4053-4063}, abstract = {

To characterize experimentally the ruggedness of the free energy landscape of protein folding is challenging, because the distributed small free energy barriers are usually dominated by one, or a few, large activation free energy barriers. This study delineates changes in the roughness of the free energy landscape by making use of the observation that a decrease in ruggedness is accompanied invariably by an increase in folding cooperativity. Hydrogen exchange (HX) coupled to mass spectrometry was used to detect transient sampling of local energy minima and the global unfolded state on the free energy landscape of the small protein single-chain monellin. Under native conditions, local noncooperative openings result in interconversions between Boltzmann-distributed intermediate states, populated on an extremely rugged "uphill" energy landscape. The cooperativity of these interconversions was increased by selectively destabilizing the native state via mutations, and further by the addition of a chemical denaturant. The perturbation of stability alone resulted in seven backbone amide sites exchanging cooperatively. The size of the cooperatively exchanging and/or unfolding unit did not depend on the extent of protein destabilization. Only upon the addition of a denaturant to a destabilized mutant variant did seven additional backbone amide sites exchange cooperatively. Segmentwise analysis of the HX kinetics of the mutant variants further confirmed that the observed increase in cooperativity was due to the smoothing of the ruggedness of the free energy landscape of folding of the protein by the chemical denaturant.

}, keywords = {Amino Acid Substitution, Deuterium Exchange Measurement, Energy Transfer, Guanidine, Indicators and Reagents, Kinetics, Menispermaceae, Models, Molecular, Mutagenesis, Site-Directed, Mutation, Plant Proteins, Protein Conformation, Protein Denaturation, Protein Folding, Protein Stability, Thermodynamics}, issn = {1520-4995}, doi = {10.1021/acs.biochem.7b00367}, author = {Malhotra, Pooja and Jethva, Prashant N and Udgaonkar, Jayant B} } @article {26659, title = {Climatic and geographic barriers drive distributional patterns of bird phenotypes within peninsular India}, journal = {Journal of Avian Biology}, volume = {48}, year = {2017}, month = {05/2017}, pages = {620-630}, abstract = {

Modern phylogenetic data provide unparalleled ability to test biogeographic paradigms, often suggested by differences in species distribution patterns. However, such approaches have been applied less at regional scales, particularly in Asia. In the absence of such data, we examine if concordance of distributional patterns for phenotypes (subspecies) suggest potential biogeographic barriers for birds in peninsular India. Specifically, we examine climatic and physical factors that might limit phenotype distributions in this region.

Various physical, vegetation and climatic barriers were demarcated to identify potential biogeographic units within peninsular India. We then collated occurrence of endemic or disjunctly distributed species and subspecies within these units using published range maps. We also quantified turnover between potential units, allowing us to identify significant biogeographic barriers. Three time-step climate data (Last Glacial Maxima, mid-Holocene and present) enabled us to examine differences between these potential biogeographic regions through time.

The Palk Straits, followed by the Goa Gap (\~{} 16{\textdegree}N) and the Godavari River emerged as the major barriers in this region. The Palk Straits and Godavari are physical barriers while Goa Gap appears to be a climate-mediated ecological divide. Mountain barriers like the Palghat Gap are not the most significant barriers as previously thought. Climatically intermediate regions appeared unstable in the past and showed inconsistent affinities to different geographic units across families. We suggest that relative climatic stability of the wet regions of the southern western Ghats could be responsible for high subspecies endemism here. Our approach provides hypotheses that can be tested with comparative multi-species phylogeographic data in the future.

}, doi = {10.1111/jav.01278}, author = {Ramachandran, V and Robin, V V and Tamma, Krishnapriya and Ramakrishnan, Uma} } @article {25249, title = {Co-expression of Tbx6 and Sox2 identifies a novel transient neuromesoderm progenitor cell state.}, journal = {Development}, year = {2017}, month = {2017 Oct 30}, abstract = {

The elongation of body axis during development is a key aspect of body plan. Bi-potential neuromesoderm progenitors (NMPs) ensure the axial growth of embryos by contributing both to the spinal cord and mesoderm. The current model for the mechanism controlling NMP deployment invokes Tbx6, a T-box factor, to drive mesoderm differentiation of NMPs. Here, we identify a new population of Tbx6+ cells in a subdomain of NMP niche in mouse embryos. Based on co-expression of a progenitor marker Sox2, we identify this population to represent a transient cell state in the mesoderm-fated NMP lineage. Genetic lineage tracing confirms the presence of Tbx6+ NMP cell state. Furthermore, we report a novel aspect of documented Tbx6 mutant phenotype, i.e., an increase from two to four ectopic neural tubes, corresponding to the switch in NMP niche, highlighting the importance of Tbx6 function in NMP fate decision. This study emphasizes the function of Tbx6 as the bi-stable switch turning mesoderm fate "on" and progenitor state "off", and thus, has implications for the molecular mechanism driving NMP fate choice.

}, issn = {1477-9129}, doi = {10.1242/dev.153262}, author = {Javali, Alok and Misra, Aritra and Leonavicius, Karolis and Acharya, Debalina and Vyas, Bhakti and Sambasivan, Ramkumar} } @article {26268, title = {Comment on "The extent of forest in dryland biomes".}, journal = {Science}, volume = {358}, year = {2017}, month = {2017 11 17}, abstract = {

Bastin et al (Reports, 12 May 2017, p. 635) infer forest as more globally extensive than previously estimated using tree cover data. However, their forest definition does not reflect ecosystem function or biotic composition. These structural and climatic definitions inflate forest estimates across the tropics and undermine conservation goals, leading to inappropriate management policies and practices in tropical grassy ecosystems.

}, issn = {1095-9203}, doi = {10.1126/science.aao1309}, author = {Griffith, Daniel M and Lehmann, Caroline E R and Str{\"o}mberg, Caroline A E and Parr, Catherine L and Pennington, R Toby and Sankaran, Mahesh and Ratnam, Jayashree and Still, Christopher J and Powell, Rebecca L and Hanan, Niall P and Nippert, Jesse B and Osborne, Colin P and Good, Stephen P and Anderson, T Michael and Holdo, Ricardo M and Veldman, Joseph W and Durigan, Giselda and Tomlinson, Kyle W and Hoffmann, William A and Archibald, Sally and Bond, William J} } @article {23142, title = {Computational genome-wide survey of odorant receptors from two solitary bees Dufourea novaeangliae (Hymenoptera: Halictidae) and Habropoda laboriosa (Hymenoptera: Apidae).}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Sep 07}, pages = {10823}, abstract = {

Olfactory/odorant receptors (ORs) probably govern eusocial behaviour in honey bees through detection of cuticular hydrocarbons (CHCs) and queen mandibular gland pheromones (QMP). CHCs are involved in nest-mate recognition whereas QMP acts as sex pheromone for drones and as retinue pheromone for female workers. Further studies on the effect of eusociality on the evolution of ORs are hindered by the non-availability of comprehensive OR sets of solitary species. We report complete OR repertoires from two solitary bees Dufourea novaeangliae (112 ORs) and Habropoda laboriosa (151 ORs). We classify these ORs into 34 phylogenetic clades/subfamilies. Differences in the OR sets of solitary and eusocial bees are observed in individual subfamilies like subfamily 9-exon (putative CHC receptors) and L (contains putative QMP receptor group). A subfamily (H) including putative floral scent receptors is expanded in the generalist honey bees only, but not in the specialists. On the contrary, subfamily J is expanded in all bees irrespective of their degree of social complexity or food preferences. Finally, we show species-lineage specific and OR-subfamily specific differences in the putative cis-regulatory DNA motifs of the ORs from six hymenopteran species. Out of these, [A/G]CGCAAGCG[C/T] is a candidate master transcription factor binding site for multiple olfactory genes.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-11098-z}, author = {Karpe, Snehal D and Dhingra, Surbhi and Brockmann, Axel and Sowdhamini, R} } @article {16564, title = {Conformational Dynamics and Allostery in E2:E3 Interactions Drive Ubiquitination: gp78 and Ube2g2.}, journal = {Structure}, year = {2017}, month = {2017 Apr 13}, abstract = {

Conformational dynamics plays a fundamental role in molecular recognition and activity in enzymes. The ubiquitin-conjugating enzyme (E2) Ube2g2 functions with the ubiquitin ligase (E3) gp78 to assemble poly-ubiquitin chains on target substrates. Two domains in gp78, RING and G2BR, bind to two distant regions of Ube2g2, and activate it for ubiquitin (Ub) transfer. G2BR increases the affinity between the RING and Ube2g2 by 50-fold, while the RING catalyzes the transfer of Ub from the Ube2g2\~{}Ub conjugate. How G2BR and RING activate Ube2g2 is unclear. In this work, conformational dynamics in Ube2g2 revealed a clear correlation of binding G2BR and RING with the sequential progression toward Ub transfer. The interrelationship of the existence and exchange between ground and excited states leads to a dynamic energy landscape model, in which redistribution of populations\ contributes to allostery and activation. These findings provide insight into gp78{\textquoteright}s modulation of conformational exchange in Ube2g2 to stimulate ubiquitination.

}, issn = {1878-4186}, doi = {10.1016/j.str.2017.03.016}, author = {Chakrabarti, Kalyan S and Li, Jess and Das, Ranabir and Byrd, R Andrew} } @article {25708, title = {Conservation priorities for endangered Indian tigers through a genomic lens.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Aug 29}, pages = {9614}, abstract = {

Tigers have lost 93\% of their historical range worldwide. India plays a vital role in the conservation of tigers since nearly 60\% of all wild tigers are currently found here. However, as protected areas are small (\<300 km(2) on average), with only a few individuals in each, many of them may not be independently viable. It is thus important to identify and conserve genetically connected populations, as well as to maintain connectivity within them. We collected samples from wild tigers (Panthera tigris tigris) across India and used genome-wide SNPs to infer genetic connectivity. We genotyped 10,184 SNPs from 38 individuals across 17 protected areas and identified three genetically distinct clusters (corresponding to northwest, southern and central India). The northwest cluster was isolated with low variation and high relatedness. The geographically large central cluster included tigers from central, northeastern and northern India, and had the highest variation. Most genetic diversity (62\%) was shared among clusters, while unique variation was highest in the central cluster (8.5\%) and lowest in the northwestern one (2\%). We did not detect signatures of differential selection or local adaptation. We highlight that the northwest population requires conservation attention to ensure persistence of these tigers.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-09748-3}, author = {Natesh, Meghana and Atla, Goutham and Nigam, Parag and Jhala, Yadvendradev V and Zachariah, Arun and Borthakur, Udayan and Ramakrishnan, Uma} } @article {24297, title = {Control of protein translation by IP3R-mediated Ca(2+) release in Drosophila neuroendocrine cells.}, journal = {Fly (Austin)}, year = {2017}, month = {2017 Sep 26}, abstract = {

The inositol 1,4,5-trisphosphate receptor (IP3R) is one of two Ca(2+) channels that gates Ca(2+) release from ER-stores. The ligand IP3, generated upon specific G-protein coupled receptor activation, binds to IP3R to release Ca(2+) into the cytosol. IP3R also mediates ER-store Ca(2+) release into the mitochondria, under basal as well as stimulatory conditions; an activity that influences cellular bioenergetics and thus, cellular growth and proliferation. In Drosophila neuroendocrine cells expressing a hypomorphic mutant of IP3R, we observed reduced protein translation levels. Here, we discuss the possible molecular mechanism for this observation. We hypothesise that the cellular energy sensor, AMPK connects IP3R mediated Ca(2+) release into the mitochondria, to protein translation, via the TOR pathway.

}, issn = {1933-6942}, doi = {10.1080/19336934.2017.1384103}, author = {Hasan, Gaiti} } @article {17522, title = {CRISPR-Cas-Induced Mutants Identify a Requirement for dSTIM in Larval Dopaminergic Cells of Drosophila melanogaster.}, journal = {G3 (Bethesda)}, volume = {7}, year = {2017}, month = {2017 Mar 10}, pages = {923-933}, abstract = {

Molecular components of store-operated calcium entry have been identified in the recent past and consist of the endoplasmic reticulum (ER) membrane-resident calcium sensor STIM and the plasma membrane-localized calcium channel Orai. The physiological function of STIM and Orai is best defined in vertebrate immune cells. However, genetic studies with RNAi strains in Drosophila suggest a role in neuronal development and function. We generated a CRISPR-Cas-mediated deletion for the gene encoding STIM in Drosophila (dSTIM), which we demonstrate is larval lethal. To study STIM function in neurons, we merged the CRISPR-Cas9 method with the UAS-GAL4 system to generate either tissue- or cell type-specific inducible STIM knockouts (KOs). Our data identify an essential role for STIM in larval dopaminergic cells. The molecular basis for this cell-specific requirement needs further investigation.

}, issn = {2160-1836}, doi = {10.1534/g3.116.038539}, author = {Pathak, Trayambak and Trivedi, Deepti and Hasan, Gaiti} } @article {27275, title = {CRISPR-Cas-Mediated Gene Silencing Reveals RacR To Be a Negative Regulator of YdaS and YdaT Toxins in Escherichia coli K-12.}, journal = {mSphere}, volume = {2}, year = {2017}, month = {2017 Nov-Dec}, abstract = {

Bacterial genomes are rich in horizontally acquired prophages. racR is an essential gene located in the rac prophage that is resident in many Escherichia coli genomes. Employing a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-based gene silencing approach, we show that RacR is a negative regulator of the divergently transcribed and adjacent ydaS-ydaT operon in Escherichia coli K-12. Overexpression of YdaS and YdaT due to RacR depletion leads to cell division defects and decrease in survival. We further show that both YdaS and YdaT can act independently as toxins and that RacR serves to counteract the toxicity by tightly downregulating the expression of these toxins. IMPORTANCEracR is an essential gene and one of the many poorly studied genes found on the rac prophage element that is present in many Escherichia coli genomes. Employing a CRISPR-based approach, we have silenced racR expression to various levels and elucidated its physiological consequences. We show that the downregulation of racR leads to upregulation of the adjacent ydaS-ydaT operon. Both YdaS and YdaT act as toxins by perturbing the cell division resulting in enhanced cell killing. This work establishes a physiological role for RacR, which is to keep the toxic effects of YdaS and YdaT in check and promote cell survival. We, thus, provide a rationale for the essentiality of racR in Escherichia coli K-12 strains.

}, issn = {2379-5042}, doi = {10.1128/mSphere.00483-17}, author = {Bindal, Gargi and Krishnamurthi, Revathy and Seshasayee, Aswin Sai Narain and Rath, Devashish} } @article {22019, title = {Cytoplasmic poly (A) binding protein (PABPC2) critically regulates epidermal maintenance and turnover in planarian Schmidtea mediterranea.}, journal = {Development}, year = {2017}, month = {2017 Aug 14}, abstract = {

Identifying key cellular events that facilitate stem cell function and tissue organization is critical for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic Poly A binding protein, SMED-PABPC2. Knockdown (KD) of Smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggested epidermal lineage transcripts, including zfp-1, to be translationally regulated by SMED-PABPC2. Together, our results uncover a novel role of SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing, and subsequent processes for regeneration.

}, issn = {1477-9129}, doi = {10.1242/dev.152942}, author = {Bansal, Dhiru and Kulkarni, Jahnavi and Nadahalli, Kavana and Lakshmanan, Vairavan and Krishna, Srikar and Sasidharan, Vidyanand and Geo, Jini and Dilipkumar, Shilpa and Pasricha, Renu and Gulyani, Akash and Raghavan, Srikala and Palakodeti, Dasaradhi} } @article {22810, title = {Data-analysis strategies for image-based cell profiling.}, journal = {Nat Methods}, volume = {14}, year = {2017}, month = {2017 Aug 31}, pages = {849-863}, abstract = {

Image-based cell profiling is a high-throughput strategy for the quantification of phenotypic differences among a variety of cell populations. It paves the way to studying biological systems on a large scale by using chemical and genetic perturbations. The general workflow for this technology involves image acquisition with high-throughput microscopy systems and subsequent image processing and analysis. Here, we introduce the steps required to create high-quality image-based (i.e., morphological) profiles from a collection of microscopy images. We recommend techniques that have proven useful in each stage of the data analysis process, on the basis of the experience of 20 laboratories worldwide that are refining their image-based cell-profiling methodologies in pursuit of biological discovery. The recommended techniques cover alternatives that may suit various biological goals, experimental designs, and laboratories{\textquoteright} preferences.

}, issn = {1548-7105}, doi = {10.1038/nmeth.4397}, author = {Caicedo, Juan C and Cooper, Sam and Heigwer, Florian and Warchal, Scott and Qiu, Peng and Molnar, Csaba and Vasilevich, Aliaksei S and Barry, Joseph D and Bansal, Harmanjit Singh and Kraus, Oren and Wawer, Mathias and Paavolainen, Lassi and Herrmann, Markus D and Rohban, Mohammad and Hung, Jane and Hennig, Holger and Concannon, John and Smith, Ian and Clemons, Paul A and Singh, Shantanu and Rees, Paul and Horvath, Peter and Linington, Roger G and Carpenter, Anne E} } @article {26675, title = {The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project}, journal = {Ecology and Evolution}, volume = {7}, year = {2017}, month = {01/2017}, pages = {145-188}, abstract = {

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

}, doi = {10.1002/ece3.2579}, author = {Hudson, LN and Newbold, T and Contu, S and Hill, SLL and Kumar, Ajith} } @article {28244, title = { Description of a new species of Liocheles Sundevall, 1833 (Hormuridae) from India}, journal = {Zootaxa}, volume = {4365}, year = {2017}, month = {12/2017}, pages = {217-230}, abstract = {

Scorpions of the genus Liocheles Sundevall, 1833 are widespread in forests of the Indo-Pacific region; however, its species diversity is poorly resolved. A new species of the genus Liocheles is herein described from northeast India after examination of freshly collected specimens and available museum material. The new species, Liocheles schalleri sp. nov., occurs in the Indo-Burma biodiversity hotspot, a region that has been poorly explored for its arachnid diversity.

}, doi = {10.11646/zootaxa.4365.2.6}, author = {Mirza, Zeeshan A} } @article {33714, title = {Description of a new species of Liocheles Sundevall, 1833 (Hormuridae) from India.}, journal = {Zootaxa}, volume = {4365}, year = {2017}, month = {2017 Dec 17}, pages = {217-230}, abstract = {

Scorpions of the genus Liocheles Sundevall, 1833 are widespread in forests of the Indo-Pacific region; however, its species diversity is poorly resolved. A new species of the genus Liocheles is herein described from northeast India after examination of freshly collected specimens and available museum material. The new species, Liocheles schalleri sp. nov., occurs in the Indo-Burma biodiversity hotspot, a region that has been poorly explored for its arachnid diversity.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4365.2.6}, author = {Mirza, Zeeshan A} } @article {25257, title = {Design and Synthesis of Cyclic Mismatch-Binding Ligands (CMBLs) with Variable Linkers by Ring-Closing Metathesis and their Photophysical and DNA Repeat Binding Properties.}, journal = {Chemistry}, volume = {23}, year = {2017}, month = {2017 Aug 22}, pages = {11385-11396}, abstract = {

Cyclophane-containing bis(2-amino-1,8-naphthyridine) moieties attached to variable linkers at the C2-position (linker B) were synthesized as cyclic mismatch-binding ligands (CMBLs). Ring-closing metathesis (RCM) is used as a key step for the introduction of double bonds at the linker B. Decreasing the size of the linker of the substrate, formation of the RCM products with an increasing trans/cis (E/Z) ratio was observed with moderate to high overall yields. Concentration-dependent fluorescence spectra were observed for CMBLs with longer linkers (n=3), whereas concentration-independent spectra were observed for CMBLs with shorter linkers (n=2 and/or 1) with a marked exception of the E-alkene 6 a. Concomitant changes in the absorption as well as in the fluorescence spectra were also observed for the CMBLs with an increasing hydrophobicity of the solvent. Absorption and fluorescence spectra of the CMBLs in solutions containing 99-100 \% methanol resembled to that of the monomer. The binding behavior of these CMBLs with repeat DNA structures was investigated by using a surface plasmon resonance (SPR) assay and circular dichroism (CD) spectra. The cyclic E-alkenes 1 a (n=3) and 3 a (n=2) show an orthogonal binding relationship with d(CCTG)9 and d(CAG)9 . However, the selectivity for the cyclic Z-alkenes increased with decreasing the length of the linker from compound 2 b (n=3) to compound 7 b (n=1). These compounds display a large molecular diversity, which allowed the tuning of the binding affinity and selectivity of the CMBLs by varying the linkers towards various biologically significant repeat DNA structures.

}, issn = {1521-3765}, doi = {10.1002/chem.201702064}, author = {Mukherjee, Sanjukta and Dohno, Chikara and Nakatani, Kazuhiko} } @article {21469, title = {Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.}, journal = {J Physiol}, year = {2017}, month = {2017 Aug 07}, abstract = {

The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of dopamine effect on intracellular signalling remains poorly understood. We used genetically-encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation level, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate in a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of Protein Phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a "tone-sensing" mode, allowing them to detect transient dips in basal dopamine. Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought. This article is protected by copyright. All rights reserved.

}, issn = {1469-7793}, doi = {10.1113/JP274475}, author = {Yapo, Cedric and Nair, Anu G and Clement, Lorna and Castro, Liliana R and Hellgren Kotaleski, Jeanette and Vincent, Pierre} } @article {21472, title = {Direct transfer of classical non-separable states into hybrid entangled two photon states.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Aug 04}, pages = {7331}, abstract = {

Hybrid entangled states, having entanglement between different degrees-of-freedom (DoF) of a particle pair, are of great interest for quantum information science and communication protocols. Among different DoFs, the hybrid entangled states encoded with polarization and orbital angular momentum (OAM) allow the generation of qubit-qudit entangled states, macroscopic entanglement with very high quanta of OAM and improvement in angular resolution in remote sensing. Till date, such hybrid entangled states are generated by using a high-fidelity polarization entangled states and subsequent imprinting of chosen amount of OAM using suitable mode converters such as spatial light modulator in complicated experimental schemes. Given that the entangled sources have feeble number of photons, loss of photons during imprinting of OAM using diffractive optical elements limits the use of such hybrid states for practical applications. Here we report, on a simple generic experimental scheme to generate hybrid entangled states in polarization and OAM through direct transfer of classical non-separable states of the pump beam in parametric down conversion process. As a proof of principle, using local non-separable pump states of OAM mode l = 3, we have produced quantum hybrid entangled states with entanglement witness parameter of ~1.25 {\textpm} 0.03 violating by 8 standard deviation.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-07318-1}, author = {Jabir, M V and Apurv Chaitanya, N and Mathew, Manoj and Samanta, G K} } @article {28246, title = {Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Dec 11}, pages = {2047}, abstract = {

Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, {\r A}-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-01848-y}, author = {Nordenfelt, Pontus and Moore, Travis I and Mehta, Shalin B and Kalappurakkal, Joseph Mathew and Swaminathan, Vinay and Koga, Nobuyasu and Lambert, Talley J and Baker, David and Waters, Jennifer C and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Waterman, Clare M and Springer, Timothy A} } @article {20328, title = {Discovering vesicle traffic network constraints by model checking.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0180692}, abstract = {

A eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic. The whole structure can be represented as a transport graph: each organelle is a node, and each vesicle route is a directed edge. What constraints must such a graph satisfy, if it is to represent a biologically realizable vesicle traffic network? Graph connectedness is an informative feature: 2-connectedness is necessary and sufficient for mass balance, but stronger conditions are required to ensure correct molecular specificity. Here we use Boolean satisfiability (SAT) and model checking as a framework to discover and verify graph constraints. The poor scalability of SAT model checkers often prevents their broad application. By exploiting the special structure of the problem, we scale our model checker to vesicle traffic systems with reasonably large numbers of molecules and compartments. This allows us to test a range of hypotheses about graph connectivity, which can later be proved in full generality by other methods.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0180692}, author = {Shukla, Ankit and Bhattacharyya, Arnab and Kuppusamy, Lakshmanan and Srivas, Mandayam and Thattai, Mukund} } @article {14978, title = {A DNA-Based T Cell Receptor Reveals a Role for Receptor Clustering in Ligand Discrimination.}, journal = {Cell}, volume = {169}, year = {2017}, month = {2017 Mar 23}, pages = {108-119.e20}, abstract = {

A T\ cell mounts an immune response by measuring the binding strength of its T\ cell receptor (TCR) for peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T\ cells convert the lifetime of the extracellular TCR-pMHC interaction into an intracellular signal remains unknown. Here, we developed a synthetic signaling system in which the extracellular domains of the TCR and pMHC were replaced with short hybridizing strands of DNA. Remarkably, T\ cells can discriminate between DNA ligands differing by a single base pair. Single-molecule imaging reveals that signaling is initiated when single ligand-bound receptors are converted into clusters, a time-dependent process requiring ligands with longer bound times. A computation model reveals that receptor clustering serves a kinetic proofreading function, enabling ligands with longer bound times to have disproportionally greater signaling outputs. These results suggest that spatial reorganization of receptors plays an important role in ligand discrimination in T\ cell signaling.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2017.03.006}, author = {Taylor, Marcus J and Husain, Kabir and Gartner, Zev J and Mayor, Satyajit and Vale, Ronald D} } @article {26579, title = {A dominant dwarf shrub increases diversity of herbaceous plant communities in a Trans-Himalayan rangeland}, journal = {Plant Ecology}, volume = {218}, year = {2017}, month = {07/2017}, pages = {843{\textendash}854}, abstract = {

Plant communities are structured by both competition and facilitation. The interplay between the two interactions can vary depending on environmental factors, nature of stress, and plant traits. However, whether positive or negative interactions dominate in regions of high biotic and abiotic stress remains unclear. We studied herbaceous plant communities associated with a dwarf shrub Caragana versicolor in semi-arid, high altitude Trans-Himalayan rangelands of Spiti, India. We surveyed 120 pairs of plots (within and outside shrub canopies) across four watersheds differing in altitude, aspect, and dominant herbivores. Herbaceous communities within shrub canopies had 25\% higher species richness, but similar abundance when compared to communities outside the canopy, with the shrub edge having higher diversity than the centre of the canopy. Grasses and erect forbs showed positive associations with the shrub, while prostrate plants occurred at much lower abundance within the canopy. Rare species showed stronger positive associations with Caragana than abundant species. Experimental removal of herbaceous vegetation from within shrub canopies led to 42\% increase in flowering in Caragana, indicating a cost to the host shrubs. Our study indicates a robust pattern of a dwarf shrub facilitating local community diversity across this alpine landscape, increasing diversity at the plot level, facilitating rare species, and yet incurring a cost to hosts from the presence of herbaceous plants. Given these large influences of this shrub on the vegetation of these high altitude rangelands, we suggest that the shrub microhabitat be explicitly considered in any analyses of ecosystem health in such rangelands.

}, doi = {10.1007/s11258-017-0734-x}, author = {Iyengar, Siddharth B and Bagchi. Sumanta and Barua, Deepak and Mishra, Charudutt and Sankaran, Mahesh} } @article {26280, title = {Drosophila adult muscle development and regeneration.}, journal = {Semin Cell Dev Biol}, year = {2017}, month = {2017 Nov 16}, abstract = {

Myogenesis is a highly orchestrated, complex developmental process by which cell lineages that are mesodermal in origin generate differentiated multinucleate muscle cells as a final product. Considerable insight into the process of myogenesis has been obtained for the embryonic development of the larval muscles of Drosophila. More recently, the postembryonic development of the muscles of the adult fly has become a focus of experimental investigation of myogenesis since specific flight muscles of the fly manifest remarkable similarities to vertebrate muscles in their development and organization. In this review, we catalog some of the milestones in the study of myogenesis in the large adult-specific flight muscles of Drosophila. The identification of mesoderm-derived muscle stem cell lineages, the characterization of the symmetric and asymmetric divisions through which they produce adult-specific myoblasts, the multifaceted processes of myoblast fusion, and the unexpected discovery of quiescent satellite cells that can be activated by injury are discussed. Moreover, the finding that all of these processes incorporate a plethora of signaling interactions with other myogenic cells and with niche-like neighboring tissue is considered. Finally, we briefly point out possible future developments in the area of Drosophila myogenesis that may lead to of new avenues of genetic research into the roles of muscle stem cells in development, disease and aging.

}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2017.11.017}, author = {Gunage, Rajesh D and Dhanyasi, Nagaraju and Reichert, Heinrich and VijayRaghavan, K} } @article {20329, title = {A Dry Transition State More Compact Than the Native State Is Stabilized by Non-Native Interactions during the Unfolding of a Small Protein.}, journal = {Biochemistry}, year = {2017}, month = {2017 Jul 11}, abstract = {

Defining the role of non-native interactions in directing the course of protein folding or unfolding reactions has been a difficult challenge. In particular, the extent to which such interactions play a productive role by stabilizing the structures of transition states (TSs) found on the folding and unfolding pathways of proteins is not known. On the contrary, it is thought that the TSs are expanded forms of the N state stabilized by native interactions, and it is not known whether non-native interactions can modulate TS structure. In this study of the unfolding of the SH3 domain of PI3 kinase using a microsecond mixing methodology, partial non-native structure formation is shown to occur initially during unfolding. The TS of this partial "folding during unfolding" reaction is more compact than the N state: the apparent rate constant of Trp53 burial during this reaction decreases with an increase in denaturant concentration. Kinetic studies of the unfolding of mutant variants suggest that the unusually compact TS is stabilized by interactions not present in N and that these non-native interactions are hydrophobic in nature. It was determined that mutation could be used to tune the degree of compaction in the TS.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.7b00388}, author = {Sen, Sreemantee and Goluguri, Rama Reddy and Udgaonkar, Jayant B} } @article {14686, title = {Early-life inflammation, immune response and ageing.}, journal = {Proc Biol Sci}, volume = {284}, year = {2017}, month = {2017 Mar 15}, abstract = {

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response.

}, issn = {1471-2954}, doi = {10.1098/rspb.2017.0125}, author = {Khan, Imroze and Agashe, Deepa and Rolff, Jens} } @article {18676, title = {Editorial-Sequences and topology.}, journal = {Curr Opin Struct Biol}, year = {2017}, month = {2017 Jun 03}, issn = {1879-033X}, doi = {10.1016/j.sbi.2017.05.006}, author = {Sowdhamini, R and Mizuguchi, Kenji} } @article {14057, title = {Emergent Structures in an Active Polar Fluid: Dynamics of Shape, Scattering, and Merger.}, journal = {Phys Rev Lett}, volume = {118}, year = {2017}, month = {2017 Feb 17}, pages = {078104}, abstract = {

Spatially localized defect structures emerge spontaneously in a hydrodynamic description of an active polar fluid comprising polar "actin" filaments and "myosin" motor proteins that (un)bind to filaments and exert active contractile stresses. These emergent defect structures are characterized by distinct textures and can be either static or mobile-we derive effective equations of motion for these "extended particles" and analyze their shape, kinetics, interactions, and scattering. Depending on the impact parameter and propulsion speed, these active defects undergo elastic scattering or merger. Our results are relevant for the dynamics of actomyosin-dense structures at the cell cortex, reconstituted actomyosin complexes, and 2D active colloidal gels.

}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.118.078104}, author = {Husain, Kabir and Rao, Madan} } @article {13640, title = {Eppur si vola (and yet it flies).}, journal = {J Exp Biol}, volume = {220}, year = {2017}, month = {2017 Feb 15}, pages = {514-516}, issn = {1477-9145}, doi = {10.1242/jeb.151324}, author = {Sane, Sanjay P} } @article {16566, title = {Evolutionary Assembly of Communities in Butterfly Mimicry Rings.}, journal = {Am Nat}, volume = {189}, year = {2017}, month = {2017 Apr}, pages = {E58-E76}, abstract = {

Species co-occurrence in ecological communities is thought to be influenced by multiple ecological and evolutionary processes, especially colonization and competition. However, effects of other interspecific interactions and evolutionary relationships are less explored. We examined evolutionary histories of community members and roles of mutualistic and parasitic interactions (M{\"u}llerian and Batesian mimicry, respectively) in the assembly of mimetic butterfly communities called mimicry rings in tropical forests of the Western Ghats, India. We found that M{\"u}llerian mimics were phylogenetically clustered, sharing aposematic signals due to common ancestry. On the other hand, Batesian mimics joined mimicry rings through convergent evolution and random phylogenetic assembly. Since the Western Ghats are a habitat island, we compared species diversity and composition in its mimicry rings with those of habitat mainland to test effects of biogeographic connectivity. The Western Ghats consisted of fewer mimicry rings and an overall smaller number of aposematic species and mimics compared to habitat mainland. The depauperate mimicry rings in the Western Ghats could have resulted from stochastic processes, reflecting their long temporal and spatial isolation and trickling colonization by the mimetic butterfly communities. These results highlight how evolutionary history, biogeographic isolation, and stochastic colonization influence the evolutionary assembly and diversity of ecological communities.

}, issn = {1537-5323}, doi = {10.1086/690907}, author = {Joshi, Jahnavi and Prakash, Anupama and Kunte, Krushnamegh} } @article {27662, title = {Experimental evolution of insect immune memory versus pathogen resistance.}, journal = {Proc Biol Sci}, volume = {284}, year = {2017}, month = {2017 Dec 20}, abstract = {

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory (immune priming), whereby sublethal exposure to a pathogen enhances survival after secondary infection. Theory predicts that immune memory should evolve when the pathogen is highly virulent, or when pathogen exposure is relatively rare. However, there are no empirical tests of these hypotheses, and the adaptive benefits of immune memory relative to direct resistance against a pathogen are poorly understood. To determine the selective pressures and ecological conditions that shape immune evolution, we imposed strong pathogen selection on flour beetle (Tribolium castaneum) populations, infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt evolved high basal resistance against multiple Bt strains. By contrast, populations injected only with a high dose of live Bt evolved a less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Intriguingly, one replicate population first evolved priming and subsequently evolved basal resistance, suggesting the potential for dynamic evolution of different immune strategies. Our work is the first report showing that pathogens can select for rapid modulation of insect priming ability, allowing hosts to evolve divergent immune strategies (generalized resistance versus specific immune memory) with potentially distinct mechanisms.

}, issn = {1471-2954}, doi = {10.1098/rspb.2017.1583}, author = {Khan, Imroze and Prakash, Arun and Agashe, Deepa} } @article {20954, title = {Expression and purification of single cysteine-containing mutant variants of the mouse prion protein by oxidative refolding.}, journal = {Protein Expr Purif}, year = {2017}, month = {2017 Jul 20}, abstract = {

The folding and aggregation of proteins has been studied extensively, using multiple probes. To facilitate such experiments, introduction of spectroscopically-active moieties in to the protein of interest is often necessary. This is commonly achieved by specifically labelling cysteine residues in the protein, which are either present naturally or introduced artificially by site-directed mutagenesis. In the case of the recombinant prion protein, which is normally expressed in inclusion bodies, the presence of the native disulfide bond complicates the correct refolding of single cysteine-containing mutant variants of the protein. To overcome this major bottleneck, a simple purification strategy for single tryptophan, single cysteine-containing mutant variants of the mouse prion protein is presented, with yields comparable to that of the wild type protein. The protein(s) obtained by this method are correctly folded, with a single reduced cysteine, and the native disulfide bond between residues C178 and C213 intact. The β-sheet rich oligomers formed from these mutant variant protein(s) are identical to the wild type protein oligomer. The current strategy facilitates sample preparation for a number of high resolution spectroscopic measurements for the prion protein, which specifically require thiol labelling.

}, issn = {1096-0279}, doi = {10.1016/j.pep.2017.07.014}, author = {Sengupta, Ishita and Udgaonkar, Jayant B} } @article {17523, title = {Farming and public goods production in Caenorhabditis elegans populations.}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {2017 Feb 28}, pages = {2289-2294}, abstract = {

The ecological and evolutionary dynamics of populations are shaped by the strategies they use to produce and use resources. However, our understanding of the interplay between the genetic, behavioral, and environmental factors driving these strategies is limited. Here, we report on a Caenorhabditis elegans-Escherichia coli (worm-bacteria) experimental system in which the worm-foraging behavior leads to a redistribution of the bacterial food source, resulting in a growth advantage for both organisms, similar to that achieved via farming. We show experimentally and theoretically that the increased resource growth represents a public good that can benefit all other consumers, regardless of whether or not they are producers. Mutant worms that cannot farm bacteria benefit from farming by other worms in direct proportion to the fraction of farmers in the worm population. The farming behavior can therefore be exploited if it is associated with either energetic or survival costs. However, when the individuals compete for resources with their own type, these costs can result in an increased population density. Altogether, our findings reveal a previously unrecognized mechanism of public good production resulting from the foraging behavior of C. elegans, which has important population-level consequences. This powerful system may provide broad insight into exploration-exploitation tradeoffs, the resultant ecoevolutionary dynamics, and the underlying genetic and neurobehavioral driving forces of multispecies interactions.

}, issn = {1091-6490}, doi = {10.1073/pnas.1608961114}, author = {Thutupalli, Shashi and Uppaluri, Sravanti and Constable, George W A and Levin, Simon A and Stone, Howard A and Tarnita, Corina E and Brangwynne, Clifford P} } @article {28252, title = {The G126V Mutation in the Mouse Prion Protein Hinders Nucleation-Dependent Fibril Formation by Slowing Initial Fibril Growth and by Increasing the Critical Concentration.}, journal = {Biochemistry}, volume = {56}, year = {2017}, month = {2017 11 07}, pages = {5931-5942}, abstract = {

The middle disordered hydrophobic region of the prion protein plays a critical role in conformational conversion of the protein, with pathogenic as well as protective mutations being localized to this region. In particular, it has been shown that the G127V mutation in this region of the human prion protein (huPrP) is protective against the spread of prion disease, but the mechanism of protection remains unknown. In this study, quantitative analyses of the kinetics of fibril formation by wild-type mouse prion protein (moPrP) and G126V moPrP (equivalent to G127V huPrP) reveal important differences: the critical concentration is higher, the lag phase is longer, and the initial effective rate constant of fibril growth is slower for the mutant variant. The study offers a simple biophysical explanation for why the G127V mutation in huPrP would be protective in humans: the \~{}5-fold increase in critical concentration caused by the mutation likely results in the critical concentration (below which fibril formation cannot occur) being higher that the concentration of the protein present in and on cells in vivo.

}, keywords = {Animals, Humans, Hydrophobic and Hydrophilic Interactions, Kinetics, Mice, Models, Theoretical, Mutation, Missense, Polymerization, Prion Proteins, PrP 27-30 Protein}, issn = {1520-4995}, doi = {10.1021/acs.biochem.7b00894}, author = {Sabareesan, Ambadi Thody and Udgaonkar, Jayant B} } @article {16563, title = {Generation of an induced pluripotent stem cell line from chorionic villi of a Turner syndrome spontaneous abortion.}, journal = {Stem Cell Res}, volume = {19}, year = {2017}, month = {2017 Mar}, pages = {12-16}, abstract = {

A major cause of spontaneous abortions is chromosomal abnormality of foetal cells. We report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem cell line is transgene free, retains the original XO karyotype, expresses pluripotency markers and undergoes trilineage differentiation. This pluripotent stem cell model of Turner syndrome should serve as a tool to study the developmental abnormalities of foetus and placenta that lead to early embryo lethality and profound symptoms like infertility in 45 XO survivors.

}, issn = {1876-7753}, doi = {10.1016/j.scr.2016.12.016}, author = {Parveen, Shagufta and Panicker, M M and Gupta, Pawan Kumar} } @article {25260, title = {Genetic Structure and Phylogeography of the Leopard Cat (Prionailurus bengalensis) Inferred from Mitochondrial Genomes.}, journal = {J Hered}, volume = {108}, year = {2017}, month = {2017 06 01}, pages = {349-360}, abstract = {

The Leopard cat Prionailurus bengalensis is a habitat generalist that is widely distributed across Southeast Asia. Based on morphological traits, this species has been subdivided into 12 subspecies. Thus far, there have been few molecular studies investigating intraspecific variation, and those had been limited in geographic scope. For this reason, we aimed to study the genetic structure and evolutionary history of this species across its very large distribution range in Asia. We employed both PCR-based (short mtDNA fragments, 94 samples) and high throughput sequencing based methods (whole mitochondrial genomes, 52 samples) on archival, noninvasively collected and fresh samples to investigate the distribution of intraspecific genetic variation. Our comprehensive sampling coupled with the improved resolution of a mitochondrial genome analyses provided strong support for a deep split between Mainland and Sundaic Leopard cats. Although we identified multiple haplogroups within the species{\textquoteright} distribution, we found no matrilineal evidence for the distinction of 12 subspecies. In the context of Leopard cat biogeography, we cautiously recommend a revision of the Prionailurus bengalensis subspecific taxonomy: namely, a reduction to 4 subspecies (2 mainland and 2 Sundaic forms).

}, keywords = {Animals, Asia, Southeastern, Biological Evolution, Cytochromes b, DNA, Mitochondrial, Felidae, Genetic Variation, Genetics, Population, Genome, Mitochondrial, Haplotypes, Phylogeography, Sequence Analysis, DNA}, issn = {1465-7333}, doi = {10.1093/jhered/esx017}, author = {Patel, Riddhi P and Wutke, Saskia and Lenz, Dorina and Mukherjee, Shomita and Ramakrishnan, Uma and Veron, G{\'e}raldine and Fickel, J{\"o}rns and Wilting, Andreas and F{\"o}rster, Daniel W} } @article {8059, title = {Genetics, morphology and ecology reveal a cryptic pika lineage in the Sikkim Himalaya.}, journal = {Mol Phylogenet Evol}, volume = {106}, year = {2017}, month = {09/2016}, pages = {55-60}, abstract = {

Asian pika species are morphologically \~{}similar and have overlapping ranges. This leads to uncertainty and species misidentification in the field. Phylogenetic analyses of such misidentified samples leads to taxonomic ambiguity. The ecology of many pika species remains understudied, particularly in the Himalaya, where sympatric species could be separated by elevation and/or substrate. We sampled, measured, and acquired genetic data from pikas in the Sikkim Himalaya. Our analyses revealed a cryptic lineage, Ochotona sikimaria, previously reported as a subspecies of O. thibetana. The results support the elevation of this lineage to the species level, as it is genetically divergent from O. thibetana, as well as sister species, O. cansus (endemic to central China) and O. curzoniae (endemic to the Tibetan plateau). The Sikkim lineage diverged from its sister species{\textquoteright} about 1.7-0.8 myr ago, coincident with uplift events in the Himalaya. Our results add to the recent spate of cryptic diversity identified from the eastern Himalaya and highlight the need for further study within the Ochotonidae.

}, issn = {1095-9513}, doi = {10.1016/j.ympev.2016.09.015}, author = {Dahal, Nishma and Lissovsky, Andrey A and Lin, Zhenzhen and Solari, Katherine and Hadly, Elizabeth A and Zhan, Xiangjiang and Ramakrishnan, Uma} } @article {18677, title = {Genomewide Mutational Diversity in Escherichia coli Population Evolving in Prolonged Stationary Phase.}, journal = {mSphere}, volume = {2}, year = {2017}, month = {2017 May-Jun}, abstract = {

Prolonged stationary phase is an approximation of natural environments presenting a range of stresses. Survival in prolonged stationary phase requires alternative metabolic pathways for survival. This study describes the repertoire of mutations accumulating in starving Escherichia\ coli populations in lysogeny broth. A wide range of mutations accumulates over the course of 1\ month in stationary phase. Single nucleotide polymorphisms (SNPs) constitute 64\% of all mutations. A majority of these mutations are nonsynonymous and are located at conserved loci. There is an increase in genetic diversity in the evolving populations over time. Computer simulations of evolution in stationary phase suggest that the maximum frequency of mutations observed in our experimental populations cannot be explained by neutral drift. Moreover, there is frequent genetic parallelism across populations, suggesting that these mutations are under positive selection. Finally, functional analysis of mutations suggests that regulatory mutations are frequent targets of selection. IMPORTANCE Prolonged stationary phase in bacteria, contrary to its name, is highly dynamic, with extreme nutrient limitation as a predominant stress. Stationary-phase cultures adapt by rapidly selecting a mutation(s) that confers a growth advantage in stationary phase (GASP). The phenotypic diversity of starving E.\ coli populations has been studied in detail; however, only a few mutations that accumulate in prolonged stationary phase have been described. This study documented the spectrum of mutations appearing in Escherichia coli during 28\ days of prolonged starvation. The genetic diversity of the population increases over time in stationary phase to an extent that cannot be explained by random, neutral drift. This suggests that prolonged stationary phase offers a great model system to study adaptive evolution by natural selection.

}, doi = {10.1128/mSphere.00059-17}, author = {Chib, Savita and Ali, Farhan and Seshasayee, Aswin Sai Narain} } @article {26571, title = {Genomic data reveal a loss of diversity in two species of tuco-tucos (genus Ctenomys) following a volcanic eruption.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Nov 24}, pages = {16227}, abstract = {

Marked reductions in population size can trigger corresponding declines in genetic variation. Understanding the precise genetic consequences of such reductions, however, is often challenging due to the absence of robust pre- and post-reduction datasets. Here, we use heterochronous genomic data from samples obtained before and immediately after the 2011 eruption of the Puyehue-Cord{\'o}n Caulle volcanic complex in Patagonia to explore the genetic impacts of this event on two parapatric species of rodents, the colonial tuco-tuco (Ctenomys sociabilis) and the Patagonian tuco-tuco (C. haigi). Previous analyses using microsatellites revealed no post-eruption changes in genetic variation in C. haigi, but an unexpected increase in variation in C. sociabilis. To explore this outcome further, we used targeted gene capture to sequence over 2,000 putatively neutral regions for both species. Our data revealed that, contrary to the microsatellite analyses, the eruption was associated with a small but significant decrease in genetic variation in both species. We suggest that genome-level analyses provide greater power than traditional molecular markers to detect the genetic consequences of population size changes, particularly changes that are recent, short-term, or modest in size. Consequently, genomic analyses promise to generate important new insights into the effects of specific environmental events on demography and genetic variation.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-16430-1}, author = {Hsu, Jeremy L and Crawford, Jeremy Chase and Tammone, Mauro N and Ramakrishnan, Uma and Lacey, Eileen A and Hadly, Elizabeth A} } @article {13270, title = {Genotoxic Effects of Culture Media on Human Pluripotent Stem Cells.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Feb 08}, pages = {42222}, abstract = {

Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media. HPSCs in E8 and mTeSR had increased incidence of changes in their DNA sequence, indicating genotoxic stress, in addition to changes in nucleolar morphology and number. Addition of antioxidants to E8 and mTeSR provided only partial rescue. Our results suggest that it is essential to determine cellular ROS levels in addition to currently used criteria i.e. pluripotency markers, differentiation into all three germ layers and normal karyotype through multiple passages, in designing culture media.

}, issn = {2045-2322}, doi = {10.1038/srep42222}, author = {Prakash Bangalore, Megha and Adhikarla, Syama and Mukherjee, Odity and Panicker, Mitradas M} } @article {29622, title = {Glassy swirls of active dumbbells.}, journal = {Phys Rev E}, volume = {96}, year = {2017}, month = {2017 Oct}, pages = {042605}, abstract = {

Is an active glass different from a conventional passive glass? To address this, we study the dynamics of a dense binary mixture of soft dumbbells, each subject to an active propulsion force and thermal fluctuations. This dense assembly shows dynamical arrest, first to a translational and then to a rotational glass, as one reduces temperature T or the self-propulsion force f. We monitor the dynamics along an iso-relaxation-time contour in the (T-f) plane. We find dramatic differences both in the fragility and in the nature of dynamical heterogeneity, which characterize the onset of glass formation-the activity-induced glass exhibits large swirls or vortices, whose scale is set by activity, and it appears to diverge as one approaches the glass transition. This large collective swirling movement should have implications for collective cell migration in epithelial layers. We construct continuum hydrodynamic equations for the simulated system, and we show that the observed behavior of this growing dynamic length scale can be understood from these equations.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.96.042605}, author = {Mandal, Rituparno and Bhuyan, Pranab Jyoti and Chaudhuri, Pinaki and Rao, Madan and Dasgupta, Chandan} } @article {17320, title = {Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB.}, journal = {PLoS Genet}, volume = {13}, year = {2017}, month = {2017 May 10}, pages = {e1006783}, abstract = {

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400-2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair-the attenuation of DNA-end processing and the initiation of homology search by RecA-thereby helping to ensure that genomic integrity is maintained during DSB repair.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1006783}, author = {Badrinarayanan, Anjana and Le, Tung B K and Spille, Jan-Hendrik and Cisse, Ibrahim I and Laub, Michael T} } @article {12615, title = {Graded Structural Polymorphism in a Bacterial Thermosensor Protein.}, journal = {J Am Chem Soc}, volume = {139}, year = {2017}, month = {2017 Jan 18}, pages = {792-802}, abstract = {

Thermosensing is critical for the expression of virulence genes in pathogenic bacteria that infect warm-blooded hosts. Proteins of the Hha-family, conserved among enterobacteriaceae, have been implicated in dynamically regulating the expression of a large number of genes upon temperature shifts. However, there is little mechanistic evidence at the molecular level as to how changes in temperature are transduced into structural changes and hence the functional outcome. In this study, we delineate the conformational behavior of Cnu, a putative molecular thermosensor, employing diverse spectroscopic, calorimetric and hydrodynamic measurements. We find that Cnu displays probe-dependent unfolding in equilibrium, graded increase in structural fluctuations and temperature-dependent swelling of the dimensions of its native ensemble within the physiological range of temperatures, features that are indicative of a highly malleable native ensemble. Site-specific fluorescence and NMR experiments in combination with multiple computational approaches-statistical mechanical model, coarse-grained and all-atom MD simulations-reveal that the fourth helix of Cnu acts as a unique thermosensing module displaying varying degrees of order and orientation in response to temperature modulations while undergoing a continuous unfolding transition. Our combined experimental-computational study unravels the folding-functional landscape of a natural thermosensor protein, the molecular origins of its unfolding complexity, highlights the role of functional constraints in determining folding-mechanistic behaviors, and the design principles orchestrating the signal transduction roles of the Hha protein family.

}, issn = {1520-5126}, doi = {10.1021/jacs.6b10608}, author = {Narayan, Abhishek and Campos, Luis A and Bhatia, Sandhya and Fushman, David and Naganathan, Athi N} } @article {17946, title = {A hierarchical model for estimating the spatial distribution and abundance of animals detected by continuous-time recorders.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0176966}, abstract = {

MOTIVATION: Several spatial capture-recapture (SCR) models have been developed to estimate animal abundance by analyzing the detections of individuals in a spatial array of traps. Most of these models do not use the actual dates and times of detection, even though this information is readily available when using continuous-time recorders, such as microphones or motion-activated cameras. Instead most SCR models either partition the period of trap operation into a set of subjectively chosen discrete intervals and ignore multiple detections of the same individual within each interval, or they simply use the frequency of detections during the period of trap operation and ignore the observed times of detection. Both practices make inefficient use of potentially important information in the data.

MODEL AND DATA ANALYSIS: We developed a hierarchical SCR model to estimate the spatial distribution and abundance of animals detected with continuous-time recorders. Our model includes two kinds of point processes: a spatial process to specify the distribution of latent activity centers of individuals within the region of sampling and a temporal process to specify temporal patterns in the detections of individuals. We illustrated this SCR model by analyzing spatial and temporal patterns evident in the camera-trap detections of tigers living in and around the Nagarahole Tiger Reserve in India. We also conducted a simulation study to examine the performance of our model when analyzing data sets of greater complexity than the tiger data.

BENEFITS: Our approach provides three important benefits: First, it exploits all of the information in SCR data obtained using continuous-time recorders. Second, it is sufficiently versatile to allow the effects of both space use and behavior of animals to be specified as functions of covariates that vary over space and time. Third, it allows both the spatial distribution and abundance of individuals to be estimated, effectively providing a species distribution model, even in cases where spatial covariates of abundance are unknown or unavailable. We illustrated these benefits in the analysis of our data, which allowed us to quantify differences between nocturnal and diurnal activities of tigers and to estimate their spatial distribution and abundance across the study area. Our continuous-time SCR model allows an analyst to specify many of the ecological processes thought to be involved in the distribution, movement, and behavior of animals detected in a spatial trapping array of continuous-time recorders. We plan to extend this model to estimate the population dynamics of animals detected during multiple years of SCR surveys.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0176966}, author = {Dorazio, Robert M and Karanth, K Ullas} } @article {21471, title = {Hierarchies in light sensing and dynamic interactions between ocular and extraocular sensory networks in a flatworm.}, journal = {Sci Adv}, volume = {3}, year = {2017}, month = {2017 Jul}, pages = {e1603025}, abstract = {

Light sensing has independently evolved multiple times under diverse selective pressures but has been examined only in a handful among the millions of light-responsive organisms. Unsurprisingly, mechanistic insights into how differential light processing can cause distinct behavioral outputs are limited. We show how an organism can achieve complex light processing with a simple "eye" while also having independent but mutually interacting light sensing networks. Although planarian flatworms lack wavelength-specific eye photoreceptors, a 25 nm change in light wavelength is sufficient to completely switch their phototactic behavior. Quantitative photoassays, eye-brain confocal imaging, and RNA interference/knockdown studies reveal that flatworms are able to compare small differences in the amounts of light absorbed at the eyes through a single eye opsin and convert them into binary behavioral outputs. Because planarians can fully regenerate, eye-brain injury-regeneration studies showed that this acute light intensity sensing and processing are layered on simple light detection. Unlike intact worms, partially regenerated animals with eyes can sense light but cannot sense finer gradients. Planarians also show a "reflex-like," eye-independent (extraocular/whole-body) response to low ultraviolet A light, apart from the "processive" eye-brain-mediated (ocular) response. Competition experiments between ocular and extraocular sensory systems reveal dynamic interchanging hierarchies. In intact worms, cerebral ocular response can override the reflex-like extraocular response. However, injury-regeneration again offers a time window wherein both responses coexist, but the dominance of the ocular response is reversed. Overall, we demonstrate acute light intensity-based behavioral switching and two evolutionarily distinct but interacting light sensing networks in a regenerating organism.

}, issn = {2375-2548}, doi = {10.1126/sciadv.1603025}, author = {Shettigar, Nishan and Joshi, Asawari and Dalmeida, Rimple and Gopalkrishna, Rohini and Chakravarthy, Anirudh and Patnaik, Siddharth and Mathew, Manoj and Palakodeti, Dasaradhi and Gulyani, Akash} } @article {14058, title = {Hunting or habitat? Drivers of waterbird abundance and community structure in agricultural wetlands of southern India.}, journal = {Ambio}, year = {2017}, month = {2017 Feb 28}, abstract = {

The relative impacts of hunting and habitat on waterbird community were studied in agricultural wetlands of southern India. We surveyed wetlands to document waterbird community, and interviewed hunters to document hunting intensity, targeted species, and the motivations for hunting. Our results show that hunting leads to drastic declines in waterbird diversity and numbers, and skew the community towards smaller species. Hunting intensity, water spread, and vegetation cover were the three most important determinants of waterbird abundance and community structure. Species richness, density of piscivorous species, and medium-sized species (31-65\ cm) were most affected by hunting. Out of 53 species recorded, 47 were hunted, with a preference for larger birds. Although illegal, hunting has increased in recent years and is driven by market demand. This challenges the widely held belief that waterbird hunting in India is a low intensity, subsistence activity, and undermines the importance of agricultural wetlands in waterbird conservation.

}, issn = {1654-7209}, doi = {10.1007/s13280-017-0907-9}, author = {Ramachandran, Ramesh and Kumar, Ajith and Gopi Sundar, Kolla S and Bhalla, Ravinder Singh} } @article {25252, title = {Identification and functional characterization of muscle satellite cells in Drosophila.}, journal = {Elife}, volume = {6}, year = {2017}, month = {2017 Oct 26}, abstract = {

Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1 and engage in Notch-Delta dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells.

}, issn = {2050-084X}, doi = {10.7554/eLife.30107}, author = {Chaturvedi, Dhananjay and Reichert, Heinrich and Gunage, Rajesh D and VijayRaghavan, K} } @article {12889, title = {Identification and structural characterization of the precursor conformation of the prion protein which directly initiates misfolding and oligomerization.}, journal = {J Mol Biol}, year = {2017}, month = {2017 Jan 29}, abstract = {

To identify and structurally characterize the precursor conformation of the prion protein (PrP), from which misfolding and aggregation directly commence, has been a long-standing goal. Misfolding converts the α-helical, non-pathogenic functional form of PrP to pathogenic, β-structured oligomeric and amyloidogenic forms, which are the cause of prion diseases. Susceptibility to sporadic prion disease correlates well with the propensity of PrP to misfold to cytotoxic, proteinase-K resistant oligomeric conformations, at low pH. In this study, mutagenesis at the hydrophobic core of the mouse prion protein has been shown to stabilize a monomeric, unfolding intermediate (I), which is populated significantly at equilibrium at low pH. Importantly, the rate of formation of β-structured oligomers at low pH is found to correlate well with the extent to which this intermediate is populated. The misfolding process is limited by dimerization of I, indicating that I is the monomeric precursor conformation which directly initiates misfolding. Structural and thermodynamic characterization by native state hydrogen-deuterium exchange-mass spectrometry studies indicate that the precursor conformation is a partially unfolded form of PrP which forms under misfolding-prone solvent conditions.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2017.01.019}, author = {Moulick, Roumita and Udgaonkar, Jayant B} } @article {12202, title = {Identification of Host Fruit Volatiles from Snowberry (Symphoricarpos albus), Attractive to Rhagoletis zephyria Flies from the Western United States.}, journal = {J Chem Ecol}, year = {2017}, month = {2017 Jan 11}, abstract = {

A mixture of behaviorally active volatiles was identified from the fruit of snowberry, Symphoricarpos albus laevigatus, for Rhagoletis zephyria flies reared from snowberry fruit. A nine-component blend containing 3-methylbutan-1-ol (3\%), dimethyl trisulfide (1\%), 1-octen-3-ol (40\%), myrcene (8\%), nonanal (9\%), linalool (13\%), (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT, 6\%), decanal (15\%), and β-caryophyllene (5\%) was identified that gave consistent electroantennogram activity and was behaviorally active in flight tunnel tests. In other flight tunnel assays, snowberry flies from two sites in Washington state, USA, displayed significantly greater levels of upwind oriented flight to sources with the snowberry volatile blend compared with previously identified volatile blends from domestic apple (Malus domestica) and downy hawthorn (Crataegus mollis) fruit from the eastern USA, and domestic apple, black hawthorn (C. douglasii) and ornamental hawthorn (C. monogyna) from Washington state. Selected subtraction assays showed that whereas removal of DMNT or 1-octen-3-ol significantly reduced the level of upwind flight, removal of myrcene and β-caryophyllene, or dimethyl trisulfide alone did not significantly affect the proportion of upwind flights. Our findings add to previous studies showing that populations of Rhagoletis flies infesting different host fruit are attracted to unique mixtures of volatile compounds specific to their respective host plants. Taken together, the results support the hypothesis that differences among flies in their behavioral responses to host fruit odors represent key adaptations involved in sympatric host plant shifts, contributing to host specific mating and generating prezygotic reproductive isolation among members of the R. pomonella sibling species complex.

}, issn = {1573-1561}, doi = {10.1007/s10886-016-0814-8}, author = {Cha, Dong H and Olsson, Shannon B and Yee, Wee L and Goughnour, Robert B and Hood, Glen R and Mattsson, Monte and Schwarz, Dietmar and Feder, Jeffrey L and Linn, Charles E} } @article {20349, title = {Impact of wild prey availability on livestock predation by snow leopards.}, journal = {R Soc Open Sci}, volume = {4}, year = {2017}, month = {2017 Jun}, pages = {170026}, abstract = {

An increasing proportion of the world{\textquoteright}s poor is rearing livestock today, and the global livestock population is growing. Livestock predation by large carnivores and their retaliatory killing is becoming an economic and conservation concern. A common recommendation for carnivore conservation and for reducing predation on livestock is to increase wild prey populations based on the assumption that the carnivores will consume this alternative food. Livestock predation, however, could either reduce or intensify with increases in wild prey depending on prey choice and trends in carnivore abundance. We show that the extent of livestock predation by the endangered snow leopard Panthera uncia intensifies with increases in the density of wild ungulate prey, and subsequently stabilizes. We found that snow leopard density, estimated at seven sites, was a positive linear function of the density of wild ungulates-the preferred prey-and showed no discernible relationship with livestock density. We also found that modelled livestock predation increased with livestock density. Our results suggest that snow leopard conservation would benefit from an increase in wild ungulates, but that would intensify the problem of livestock predation for pastoralists. The potential benefits of increased wild prey abundance in reducing livestock predation can be overwhelmed by a resultant increase in snow leopard populations. Snow leopard conservation efforts aimed at facilitating increases in wild prey must be accompanied by greater assistance for better livestock protection and offsetting the economic damage caused by carnivores.

}, issn = {2054-5703}, doi = {10.1098/rsos.170026}, author = {Suryawanshi, Kulbhushansingh R and Redpath, Stephen M and Bhatnagar, Yash Veer and Ramakrishnan, Uma and Chaturvedi, Vaibhav and Smout, Sophie C and Mishra, Charudutt} } @article {22088, title = {In silico Evolution of Lysis-Lysogeny Strategies Reproduces Observed Lysogeny Propensities in Temperate Bacteriophages.}, journal = {Front Microbiol}, volume = {8}, year = {2017}, month = {2017}, pages = {1386}, abstract = {

Bacteriophages are the most abundant organisms on the planet and both lytic and temperate phages play key roles as shapers of ecosystems and drivers of bacterial evolution. Temperate phages can choose between (i) lysis: exploiting their bacterial hosts by producing multiple phage particles and releasing them by lysing the host cell, and (ii) lysogeny: establishing a potentially mutually beneficial relationship with the host by integrating their chromosome into the host cell{\textquoteright}s genome. Temperate phages exhibit lysogeny propensities in the curiously narrow range of 5-15\%. For some temperate phages, the propensity is further regulated by the multiplicity of infection, such that single infections go predominantly lytic while multiple infections go predominantly lysogenic. We ask whether these observations can be explained by selection pressures in environments where multiple phage variants compete for the same host. Our models of pairwise competition, between phage variants that differ only in their propensity to lysogenize, predict the optimal lysogeny propensity to fall within the experimentally observed range. This prediction is robust to large variation in parameters such as the phage infection rate, burst size, decision rate, as well as bacterial growth rate, and initial phage to bacteria ratio. When we compete phage variants whose lysogeny strategies are allowed to depend upon multiplicity of infection, we find that the optimal strategy is one which switches from full lysis for single infections to full lysogeny for multiple infections. Previous attempts to explain lysogeny propensity have argued for bet-hedging that optimizes the response to fluctuating environmental conditions. Our results suggest that there is an additional selection pressure for lysogeny propensity within phage populations infecting a bacterial host, independent of environmental conditions.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2017.01386}, author = {Sinha, Vaibhhav and Goyal, Akshit and Svenningsen, Sine L and Semsey, Szabolcs and Krishna, Sandeep} } @article {26570, title = {In situ modeling of multimodal floral cues attracting wild pollinators across environments.}, journal = {Proc Natl Acad Sci U S A}, year = {2017}, month = {2017 Nov 27}, abstract = {

With more than 80\% of flowering plant species specialized for animal pollination, understanding how wild pollinators utilize resources across environments can encourage efficient planting and maintenance strategies to maximize pollination and establish resilience in the face of environmental change. A fundamental question is how generalist pollinators recognize "flower objects" in vastly different ecologies and environments. On one hand, pollinators could employ a specific set of floral cues regardless of environment. Alternatively, wild pollinators could recognize an exclusive signature of cues unique to each environment or flower species. Hoverflies, which are found across the globe, are one of the most ecologically important alternative pollinators after bees and bumblebees. Here, we have exploited their cosmopolitan status to understand how wild pollinator preferences change across different continents. Without employing any a priori assumptions concerning the floral cues, we measured, predicted, and finally artificially recreated multimodal cues from individual flowers visited by hoverflies in three different environments (hemiboreal, alpine, and tropical) using a field-based methodology. We found that although "flower signatures" were unique for each environment, some multimodal lures were ubiquitously attractive, despite not carrying any reward, or resembling real flowers. While it was unexpected that cue combinations found in real flowers were not necessary, the robustness of our lures across insect species and ecologies could reflect a general strategy of resource identification for generalist pollinators. Our results provide insights into how cosmopolitan pollinators such as hoverflies identify flowers and offer specific ecologically based cues and strategies for attracting pollinators across diverse environments.

}, issn = {1091-6490}, doi = {10.1073/pnas.1714414114}, author = {Nordstr{\"o}m, Karin and Dahlbom, Josefin and Pragadheesh, V S and Ghosh, Suhrid and Olsson, Amadeus and Dyakova, Olga and Suresh, Shravanti Krishna and Olsson, Shannon B} } @article {19199, title = {Inhibitory engrams in perception and memory.}, journal = {Proc Natl Acad Sci U S A}, year = {2017}, month = {2017 Jun 13}, abstract = {

Nervous systems use excitatory cell assemblies to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or "engrams" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems create and use inhibitory replicas of excitatory representations for important cognitive functions. Such matched "inhibitory engrams" can form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli, thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for context-relevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focused disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia, and posttraumatic stress disorder.

}, issn = {1091-6490}, doi = {10.1073/pnas.1701812114}, author = {Barron, Helen C and Vogels, Tim P and Behrens, Timothy E and Ramaswami, Mani} } @article {16560, title = {Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state.}, journal = {Biol Direct}, volume = {12}, year = {2017}, month = {2017 Apr 20}, pages = {9}, abstract = {

BACKGROUND: TRIF is a key protein in antiviral innate immunity, operating downstream of TLRs. TRIF activation leads to the production of interferon-β and pro-inflammatory cytokines. There is evidence from experiments to suggest that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive activation. However, no structure of a complex between the N-terminal domain and the TIR domain exists till date. The disordered nature of the region connecting the N-terminal domain and the TIR domain compounds the issue of elucidating the mechanism of autoinhibition of TRIF. In this study, we have employed an integrative approach consisting of mutual information analysis, docking, molecular dynamics simulations and residue network analysis, in combination with existing experimental data to provide a glimpse of TRIF in its autoinhibited state.

RESULTS: Our extensive docking approach reveals that the N-terminal domain binds to the BB loop-B helix region of the TIR domain, consistent with experimental observations. Long length molecular dynamics simulations of 1 microsecond performed on the docked model highlights residues participating in hydrogen bonding and hydrophobic interactions at the interface. A pair of residues present in the vicinity of the interface is also predicted by mutual information analysis, to co-evolve. Residues mediating long-range interactions within the TIR domain of TRIF were identified using residue network analysis.

CONCLUSIONS: Based on the results of the modelling and residue network analysis, we propose that the N-terminal domain binds to the BB loop region of the TIR domain, thereby preventing its homodimersation. The binding of TRIF to TLR3 or TRAM could induce a slight conformational change, causing the interactions between the N-terminal domain and TIR domain to disrupt, thereby exposing the BB loop and rendering it amenable for higher-order oligomerisation.

REVIEWERS: This article was reviewed by Michael Gromiha, Srikrishna Subramaniam and Peter Bond (nominated by Chandra Verma).

}, issn = {1745-6150}, doi = {10.1186/s13062-017-0179-0}, author = {Mahita, Jarjapu and Sowdhamini, Ramanathan} } @article {6136, title = {Intramolecular Backbone{\textperiodcentered}{\textperiodcentered}{\textperiodcentered}Backbone Hydrogen Bonds in Polypeptide Conformations. The Other Way Around: ε-Turn.}, journal = {Biopolymers}, volume = {108}, year = {2017}, month = {01/2017}, abstract = {

In this study, we performed a detailed literature survey of the ε-turn in peptides and proteins. This 3D-structural feature is characterized by an eleven-membered pseudo-cycle closed by an intramolecular backbone{\textellipsis}backbone H-bond. Interestingly, in this motif the direction of the N-H{\textellipsis}O=C H-bond runs opposite to that of the much more popular and extensively investigated α-, β-, and γ-turns. We did not authenticate unequivocally the ε-turn main-chain reversal topology in any linear short peptide. However, it is frequently observed in small cyclic peptides formed by four, five, and six amino acid residues with stringent geometric requirements. Rather surprisingly, ε-turns do occur in proteins, although to a relatively moderate extent, as an isolated feature or in the turn segment of hairpin motifs based on two antiparallel, pleated β-strands. Moreover, the ε-turn may also host not only the seven-membered, intramolecularly H-bonded, pseudo-cycle termed γ-turn, either of the classic or inverse type, but also one (or even two) cis peptide bond(s) or a β-bulge conformation. Based on their ϕ,ψ backbone torsion angles, we were able to classify the protein ε-turns in six different families. Conformational energy computations using the DFT methodology were also performed on the ε-turns adopted by the amino acid triplet -Gly-Gly-Gly- (Gly is the most commonly found residue at each of the three positions in our analysis of proteins). Again, in this computational study, six families of turns were identified, but only some of them resemble rather closely those extracted from our investigation on proteins. This article is protected by copyright. All rights reserved.

}, issn = {1097-0282}, doi = {10.1002/bip.22911}, author = {Toniolo, Claudio and Crisma, Marco and Formaggio, Fernando and Alem{\'a}n, Carlos and Ramakrishnan, Chandrasekharan and Kalmankar, Neha and Balaram, Padmanabhan} } @article {14685, title = {IP3R mediated Ca(2+) release regulates protein metabolism in Drosophila neuroendocrine cells: implications for development under nutrient stress.}, journal = {Development}, year = {2017}, month = {2017 Mar 13}, abstract = {

Successful completion of animal development is fundamentally reliant on nutritional cues. Adaptations for surviving nutritional loss are coordinated in part by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells critically modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation, if either insulin signaling or IP3/Ca(2+) signaling, were down-regulated in NE cells. Moreover, an IP3R (Inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by over-expression of either InR (insulin receptor) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways may be functionally compensatory. Furthermore, cultured IP3R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP3R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive poor nutritional conditions.

}, issn = {1477-9129}, doi = {10.1242/dev.145235}, author = {Megha, Megha and Hasan, Gaiti} } @article {20321, title = {Large anthropogenic impacts on a charismatic small carnivore: Insights from distribution surveys of red panda Ailurus fulgens in Nepal.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0180978}, abstract = {

Protected areas are key to preserving biodiversity and maintaining ecosystem services. However, their ability to ensure long-term survival of threatened andendangered species varies across countries, regions and landscapes. Distribution surveys can beparticularly important for assessing the value of protected areas, and gauging their efficacy incatering to species-specific requirements. We assessed the conservation value of one such reserve for a charismatic yet globally endangered species, the red panda Ailurus fulgens,in the light of on-going land-use transformation in Nepal. We conducted field surveys forindirect signs of red pandas along forest trails in 25-km2 sampling grid cells (n = 54) of Dhorpatan Hunting Reserve, and confronted a set of ecological hypotheses to the data using hierarchical occupancy models. We estimated overall occupancy at Ψ(SE) = 0.41 (0.007), with relatively high site-level detectability [p = 0.93 (SE = 0.001)]. Our results show that despitebeing a subsistence form of small-scale resource use, extraction of bamboo and livestock grazing negatively affected panda occurrence, albeit at different intensities. The amount of bamboo cover,rather than the overall proportion of forest cover, had greater influence on the panda occurrence. Despite availability of bamboo cover, areas with bamboo extraction and anthropogenic disturbances were less likely to be occupied by pandas. Together, these results suggest that long-term persistence of red pandas in this reserve and elsewhere across the species{\textquoteright} range will require preventing commercial extractionof bamboo, coupled with case-specific regulation of anthropogenic exploitation of red panda habitats.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0180978}, author = {Panthi, Saroj and Khanal, Gopal and Acharya, Krishna Prasad and Aryal, Achyut and Srivathsa, Arjun} } @article {17319, title = {Leopard in a tea-cup: A study of leopard habitat-use and human-leopard interactions in north-eastern India.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0177013}, abstract = {

There is increasing evidence of the importance of multi-use landscapes for the conservation of large carnivores. However, when carnivore ranges overlap with high density of humans, there are often serious conservation challenges. This is especially true in countries like India where loss of peoples{\textquoteright} lives and property to large wildlife are not uncommon. The leopard (Panthera pardus) is a large felid that is widespread in India, often sharing landscapes with high human densities. In order to understand the ecology of leopards in a human use landscape and the nature of human-leopard interactions, we studied (i) the spatial and temporal distribution and the characteristics of leopard attacks on people, (ii) the spatial variability in the pattern of habitat use by the leopard, and (iii) the spatial relationship between attack locations and habitat use by leopards. The study site, located in northern West Bengal, India, is a densely populated mixed-use landscape of 630 km2, comprising of forests, tea plantations, agriculture fields, and human settlements. A total of 171 leopard attacks on humans were reported between January 2009 and March 2016, most of which occurred within the tea-gardens. None of the attacks was fatal. We found significant spatial clustering of locations of leopard attacks on humans. However, most of the attacks were restricted to certain tea estates and occurred mostly between January and May. Analysis of habitat use by leopards showed that the probability of use of areas with more ground vegetation cover was high while that of areas with high density of buildings was low. However, locations of leopard attacks on people did not coincide with areas that showed a higher probability of use by leopards. This indicates that an increased use of an area by leopards, by itself, does not necessarily imply an increase in attacks on people. The spatial and temporal clustering of attack locations allowed us to use this information to prioritize areas to focus mitigation activities in order reduce negative encounters between people and leopards in this landscape which has had a long history of conflict.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0177013}, author = {Kshettry, Aritra and Vaidyanathan, Srinivas and Athreya, Vidya} } @article {13639, title = {L{\'e}vy flights in the presence of a point sink of finite strength.}, journal = {Phys Rev E}, volume = {95}, year = {2017}, month = {2017 Jan}, pages = {012154}, abstract = {

In this paper, the absorption of a particle undergoing L{\'e}vy flight in the presence of a point sink of arbitrary strength and position is studied. The motion of such a particle is given by a modified Fokker-Planck equation whose exact solution in the Laplace domain can be described in terms of the Laplace transform of the unperturbed (absence of the sink) Green{\textquoteright}s function. This solution for the Green{\textquoteright}s function is a well-studied, generic result which applies to both fractional and usual Fokker-Planck equations alike. Using this result, the propagator and the absorption-time distribution are obtained for free L{\'e}vy flight and L{\'e}vy flight in linear and harmonic potentials in the presence of a delta function sink, and their dependence on the sink strength is analyzed. Analytical results are presented for the long-time behavior of the absorption-time distribution in all three above-mentioned potentials. Simulation results are found to corroborate closely with analytical results.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.95.012154}, author = {Janakiraman, Deepika} } @article {28245, title = {Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.}, journal = {Mol Biol Cell}, volume = {28}, year = {2017}, month = {2017 Dec 15}, pages = {3728-3740}, abstract = {

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD.

}, issn = {1939-4586}, doi = {10.1091/mbc.E16-09-0674}, author = {Hebbar, Sarita and Khandelwal, Avinash and Jayashree, R and Hindle, Samantha J and Chiang, Yin Ning and Yew, Joanne Y and Sweeney, Sean T and Schwudke, Dominik} } @article {24296, title = {The long 3{\textquoteright}UTR mRNA of CaMKII is essential for translation-dependent plasticity of spontaneous release in Drosophila melanogaster.}, journal = {J Neurosci}, year = {2017}, month = {2017 Sep 27}, abstract = {

A null mutation of the Drosophila calcium/calmodulin-dependent protein kinase II gene (CaMKII) was generated using homologous recombination. Null animals survive to larval and pupal stages due to a large maternal contribution of CaMKII mRNA, which consists of a short 3{\textquoteright}- u n t ranslated r egion (UTR) form lacking regulatory elements that guide local translation. The selective loss of the long 3{\textquoteright}UTR mRNA in CaMKII null larvae allows us to test its role in plasticity. Development and evoked function of the larval neuromuscular junction are surprisingly normal, but the resting rate of miniature excitatory junctional potentials (mEJPs) is significantly lower in CaMKII mutants. Mutants also lack the ability to increase mEJP rate in response to spaced depolarization, a type of activity-dependent plasticity shown to require both transcription and translation. Consistent with this, overexpression of miR-289 in wild-type animals blocks plasticity of spontaneous release. In addition to the defects in regulation of mEJP rate, CaMKII protein is largely lost from synapses in the mutant. All phenotypes are non-sex-specific and rescued by a fosmid containing the entire wild-type CaMKII locus, but only viability and CaMKII localization are rescued by genomic fosmids lacking the long 3{\textquoteright}UTR. This suggests that synaptic CaMKII accumulates by two distinct mechanisms: local synthesis requiring the long 3{\textquoteright}UTR form of CaMKII mRNA and a process which requires zygotic transcription of CaMKII mRNA. The origin of synaptic CaMKII also dictates its functionality. Locally translated CaMKII has a privileged role in regulation of spontaneous release which cannot be fulfilled by synaptic CaMKII from the other pool.SIGNIFICANCE STATEMENTAs a regulator of synaptic development and plasticity, CaMKII has important roles in both normal and pathological function of the nervous system. CaMKII shows high conservation between Drosophila and humans, underscoring the usefulness of Drosophila in modeling its function. Drosophila CaMKII null mutants remain viable throughout development, enabling morphological and electrophysiological characterization. While the structure of the synapse is normal, maternally contributed CaMKII does not localize to synapses. Zygotic production of CaMKII mRNA with a long 3{\textquoteright}UTR is necessary for modulating spontaneous neurotransmission in an activity-dependent manner, but not for viability. These data argue that regulation of CaMKII localization and levels by local transcriptional processes is conserved. This is the first demonstration of distinct functions for DrosophilaCaMKII mRNA variants.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.1313-17.2017}, author = {Kuklin, Elena A and Alkins, Stephen and Bakthavachalu, Baskar and Genco, Maria C and Sudhakaran, Indulekha and Raghavan, K Vijay and Ramaswami, Mani and Griffith, Leslie C} } @article {26664, title = {Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.}, journal = {RNA Biol}, volume = {14}, year = {2017}, month = {2017 May 04}, pages = {568-586}, abstract = {

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

}, issn = {1555-8584}, doi = {10.1080/15476286.2016.1244588}, author = {Sudhakaran, Indulekha P and Ramaswami, Mani} } @article {17945, title = {Loss of the Habenula Intrinsic Neuromodulator Kisspeptin1 Affects Learning in Larval Zebrafish.}, journal = {eNeuro}, volume = {4}, year = {2017}, month = {2017 May-Jun}, abstract = {

Learning how to actively avoid a predictable threat involves two steps: recognizing the cue that predicts upcoming punishment and learning a behavioral response that will lead to avoidance. In zebrafish, ventral habenula (vHb) neurons have been proposed to participate in both steps by encoding the expected aversiveness of a stimulus. vHb neurons increase their firing rate as expectation of punishment grows but reduce their activity as avoidance learning occurs. This leads to changes in the activity of raphe neurons, which are downstream of the vHb, during learning. How vHb activity is regulated is not known. Here, we ask whether the neuromodulator Kisspeptin1, which is expressed in the ventral habenula together with its receptor, could be involved. Kiss1 mutants were generated with CRISPR/Cas9 using guide RNAs targeted to the signal sequence. Mutants, which have a stop codon upstream of the active Kisspeptin1 peptide, have a deficiency in learning to avoid a shock that is predicted by light. Electrophysiology indicates that Kisspeptin1 has a concentration-dependent effect on vHb neurons: depolarizing at low concentrations and hyperpolarizing at high concentrations. Two-photon calcium imaging shows that mutants have reduced raphe response to shock. These data are consistent with the hypothesis that Kisspeptin1 modulates habenula neurons as the fish learns to cope with a threat. Learning a behavioral strategy to overcome a stressor may thus be accompanied by physiological change in the habenula, mediated by intrinsic neuromodulation.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0326-16.2017}, author = {Lupton, Charlotte and Sengupta, Mohini and Cheng, Ruey-Kuang and Chia, Joanne and Thirumalai, Vatsala and Jesuthasan, Suresh} } @article {15556, title = {The lysine deacetylase Sirtuin 1 modulates the localization and function of the Notch1 receptor in regulatory T cells.}, journal = {Sci Signal}, volume = {10}, year = {2017}, month = {2017 Apr 04}, abstract = {

The ability to tune cellular functions in response to nutrient availability has important consequences for immune homeostasis. The activity of the receptor Notch in regulatory T (Treg) cells, which suppress the functions of effector T cells, is indispensable for Treg cell survival under conditions of diminished nutrient supply. Anti-apoptotic signaling induced by the Notch1 intracellular domain (NIC) originates from the cytoplasm and is spatially decoupled from the nuclear, largely transcriptional functions of NIC. We showed that Sirtuin 1 (Sirt1), which is an NAD(+) (nicotinamide adenine dinucleotide)-dependent lysine deacetylase that inhibits NIC-dependent gene transcription, stabilized NIC proximal to the plasma membrane to promote the survival and function of activated Treg cells. Sirt1 was required for NIC-dependent protection from apoptosis in cell lines but not for the activity of the anti-apoptotic protein Bcl-xL. In addition, a variant NIC protein in which four lysines were mutated to arginines (NIC4KR) retained anti-apoptotic activity, but was not regulated by Sirt1, and reconstituted the functions of nonnuclear NIC in Notch1-deficient Treg cells. Loss of Sirt1 compromised Treg cell survival, resulting in antigen-induced T cell proliferation and inflammation in two mouse models. Thus, the Sirt1-Notch interaction may constitute an important checkpoint that tunes noncanonical Notch1 signaling.

}, issn = {1937-9145}, doi = {10.1126/scisignal.aah4679}, author = {Marcel, Nimi and Perumalsamy, Lakshmi R and Shukla, Sanjay K and Sarin, Apurva} } @article {16561, title = {Mechanics of the thorax in flies.}, journal = {J Exp Biol}, volume = {220}, year = {2017}, month = {2017 Apr 15}, pages = {1382-1395}, abstract = {

Insects represent more than 60\% of all multicellular life forms, and are easily among the most diverse and abundant organisms on earth. They evolved functional wings and the ability to fly, which enabled them to occupy diverse niches. Insects of the hyper-diverse orders show extreme miniaturization of their body size. The reduced body size, however, imposes steep constraints on flight ability, as their wings must flap faster to generate sufficient forces to stay aloft. Here, we discuss the various physiological and biomechanical adaptations of the thorax in flies which enabled them to overcome the myriad constraints of small body size, while ensuring very precise control of their wing motion. One such adaptation is the evolution of specialized myogenic or asynchronous muscles that power the high-frequency wing motion, in combination with neurogenic or synchronous steering muscles that control higher-order wing kinematic patterns. Additionally, passive cuticular linkages within the thorax coordinate fast and yet precise bilateral wing movement, in combination with an actively controlled clutch and gear system that enables flexible flight patterns. Thus, the study of thoracic biomechanics, along with the underlying sensory-motor processing, is central in understanding how the insect body form is adapted for flight.

}, issn = {1477-9145}, doi = {10.1242/jeb.128363}, author = {Deora, Tanvi and Gundiah, Namrata and Sane, Sanjay P} } @article {18680, title = {Mechanism of Discrimination of 8-Oxoguanosine versus Guanosine by Escherichia coli Fpg.}, journal = {J Phys Chem B}, year = {2017}, month = {2017 Jun 07}, abstract = {

The mutagenic 8-oxoguanosine monophosphate, the predominant product of DNA oxidation, is excised by formamidopyrimidine glycosylase (Fpg) in bacteria. The mechanism of recognition of 8-oxodG, which differs subtly from its normal counterpart, guanosine monophosphate (dG), by Escherichia coli Fpg remains elusive due to the lack of structural data of E. coli Fpg bound to 8-oxodG. Here, we present solution-state structure of 8-oxodG oligomer bound to E. coli E3Q Fpg using UV resonance Raman (UVRR) spectroscopy. The vibrational spectra report on the π-stacking and hydrogen bonding interactions established by 8-oxodG with E. coli E3Q Fpg. Furthermore, we report on the interactions of E. coli E3Q Fpg with the normal, undamaged nucleotide, dG. We show that E. coli Fpg recognizes 8-oxodG and dG through their C2-amino group but only 8-oxodG forms extensive contacts with E. coli Fpg. Our findings provide a basis for mechanism of lesion recognition by E. coli Fpg.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b00205}, author = {Jayanth, Namrata and Puranik, Mrinalini} } @article {13267, title = {Merging paleobiology with conservation biology to guide the future of terrestrial ecosystems.}, journal = {Science}, volume = {355}, year = {2017}, month = {2017 Feb 10}, abstract = {

Conservation of species and ecosystems is increasingly difficult because anthropogenic impacts are pervasive and accelerating. Under this rapid global change, maximizing conservation success requires a paradigm shift from maintaining ecosystems in idealized past states toward facilitating their adaptive and functional capacities, even as species ebb and flow individually. Developing effective strategies under this new paradigm will require deeper understanding of the long-term dynamics that govern ecosystem persistence and reconciliation of conflicts among approaches to conserving historical versus novel ecosystems. Integrating emerging information from conservation biology, paleobiology, and the Earth sciences is an important step forward on the path to success. Maintaining nature in all its aspects will also entail immediately addressing the overarching threats of growing human population, overconsumption, pollution, and climate change.

}, issn = {1095-9203}, doi = {10.1126/science.aah4787}, author = {Barnosky, Anthony D and Hadly, Elizabeth A and Gonzalez, Patrick and Head, Jason and Polly, P David and Lawing, A Michelle and Eronen, Jussi T and Ackerly, David D and Alex, Ken and Biber, Eric and Blois, Jessica and Brashares, Justin and Ceballos, Gerardo and Davis, Edward and Dietl, Gregory P and Dirzo, Rodolfo and Doremus, Holly and Fortelius, Mikael and Greene, Harry W and Hellmann, Jessica and Hickler, Thomas and Jackson, Stephen T and Kemp, Melissa and Koch, Paul L and Kremen, Claire and Lindsey, Emily L and Looy, Cindy and Marshall, Charles R and Mendenhall, Chase and Mulch, Andreas and Mychajliw, Alexis M and Nowak, Carsten and Ramakrishnan, Uma and Schnitzler, Jan and Das Shrestha, Kashish and Solari, Katherine and Stegner, Lynn and Stegner, M Allison and Stenseth, Nils Chr and Wake, Marvalee H and Zhang, Zhibin} } @article {16579, title = {Methylglyoxal detoxification by a DJ-1 family protein provides dual abiotic and biotic stress tolerance in transgenic plants.}, journal = {Plant Mol Biol}, year = {2017}, month = {2017 Apr 25}, abstract = {

Methylglyoxal (MG) is a key signaling molecule resulting from glycolysis and other metabolic pathways. During abiotic stress, MG levels accumulate to toxic levels in affected cells. However, MG is routinely detoxified through the action of DJ1/PARK7/Hsp31 proteins that are highly conserved across kingdoms and mutations in such genes are associated with neurodegenerative diseases. Here, we report for the first time that, similar to abiotic stresses, MG levels increase during biotic stresses in plants, likely contributing to enhanced susceptibility to a wide range of stresses. We show that overexpression of yeast Heat shock protein 31 (Hsp31), a DJ-1 homolog with robust MG detoxifying capabilities, confers dual biotic and abiotic stress tolerance in model plant Nicotiana tabacum. Strikingly, overexpression of Hsp31 in tobacco imparts robust stress tolerance against diverse biotic stress inducers such as viruses, bacteria and fungi, in addition to tolerance against a range of abiotic stress inducers. During stress, Hsp31 was targeted to mitochondria and induced expression of key stress-related genes. These results indicate that Hsp31 is a novel attractive tool to engineer plants against both biotic and abiotic stresses.

}, issn = {1573-5028}, doi = {10.1007/s11103-017-0613-9}, author = {Melvin, Prasad and Bankapalli, Kondalarao and D{\textquoteright}Silva, Patrick and Shivaprasad, P V} } @article {12201, title = {MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia.}, journal = {Cell Death Dis}, volume = {8}, year = {2017}, month = {2017 Jan 12}, pages = {e2547}, abstract = {

The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients. Earlier, miRNA182-5p upregulation was reported in several solid tumours and haematological malignancies. We undertook a strategy involving transient modulation and CRISPR/Cas9 (clustered regularly interspersed short palindromic repeats)-mediated knockout of the MIR182 locus in CML cells. The lineage contribution was assessed by methylcellulose colony formation assay. The transient modulation of miRNA182-5p revealed a biased phenotype. Strikingly, Δ182 cells (homozygous deletion of MIR182 locus) produced a marked shift in lineage distribution. The phenotype was rescued by ectopic expression of miRNA182-5p in Δ182 cells. A bioinformatic analysis and Hes1 modulation data suggested that Hes1 could be a putative target of miRNA182-5p. A reciprocal relationship between miRNA182-5p and Hes1 was seen in the context of TK inhibition. In conclusion, we reveal a key role for miRNA182-5p in restricting the myeloid development of leukemic cells. We propose that the Δ182 cell line will be valuable in designing experiments for next-generation pharmacological interventions.

}, issn = {2041-4889}, doi = {10.1038/cddis.2016.471}, author = {Arya, Deepak and Sachithanandan, Sasikala P and Ross, Cecil and Palakodeti, Dasaradhi and Li, Shang and Krishna, Sudhir} } @article {28248, title = {Modulation of Global Transcriptional Regulatory Networks as a Strategy for Increasing Kanamycin Resistance of the Translational Elongation Factor-G Mutants in Escherichia coli.}, journal = {G3 (Bethesda)}, volume = {7}, year = {2017}, month = {2017 Dec 04}, pages = {3955-3966}, abstract = {

Evolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics. In our previous work, we used short-term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin, and reported that Escherichia coli develops low cost resistance to kanamycin via different point mutations in the translation Elongation Factor-G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genes rpoD/cpxA/topA/cyaA Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance. In this work, we expand our understanding of these second site mutations, the goal being to understand how these mutations affect the activities of the mutated gene products to confer resistance. We show that the mutation in cpxA most likely results in an active Cpx stress response. Further evolution of an EF-G mutant in a higher concentration of kanamycin than what was used in our previous experiments identified the cpxA locus as a primary target for a significant increase in resistance. The mutation in cyaA results in a loss of catalytic activity and probably results in resistance via altered CRP function. Despite a reduction in cAMP levels, the CyaAN600Y mutant has a transcriptome indicative of increased CRP activity, pointing to an unknown role for CyaA and / or cAMP in gene expression. From the transcriptomes of double and single mutants, we describe the epistasis between the mutation in EF-G and these second site mutations. We show that the large scale transcriptomic changes in the topoisomerase I (FusAA608E-TopAS180L) mutant likely result from increased negative supercoiling in the cell. Finally, genes with known roles in aminoglycoside resistance were present among the misregulated genes in the mutants.

}, issn = {2160-1836}, doi = {10.1534/g3.117.300284}, author = {Mogre, Aalap and Veetil, Reshma T and Seshasayee, Aswin Sai Narain} } @article {25254, title = {Modulation of the Extent of Cooperative Structural Change During Protein Folding by Chemical Denaturant.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Sep 07}, pages = {8263-8275}, abstract = {

Protein folding and unfolding reactions invariably appear to be highly cooperative reactions, but the structural and sequence determinants of cooperativity are poorly understood. Importantly, it is not known whether cooperative structural change occurs throughout the protein, or whether some parts change cooperatively and other parts change noncooperatively. In the current study, hydrogen exchange mass spectrometry has been used to show that the mechanism of unfolding of the PI3K SH3 domain is similar in the absence and presence of 5 M urea. The data are well described by a four state N <-> IN <-> I2 <-> U model, in which structural changes occur noncooperatively during the N <-> IN and IN <-> I2 transitions, and occur cooperatively during the I2 <-> U transition. The nSrc-loop and RT-loop, as well as β strands 4 and 5 undergo noncooperative unfolding, while β strands 1, 2, and 3 unfold cooperatively in the absence of urea. However, in the presence of 5 M urea, the unfolding of β strand 4 switches to become cooperative, leading to an increase in the extent of cooperative structural change. The current study highlights the relationship between protein stability and cooperativity, by showing how the extent of cooperativity can be varied, using chemical denaturant to alter protein stability.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b04473}, author = {Jethva, Prashant N and Udgaonkar, Jayant B} } @article {21473, title = {Modulation of the extent of structural heterogeneity in α-synuclein fibrils by the small molecule thioflavin T.}, journal = {J Biol Chem}, year = {2017}, month = {2017 Jul 31}, abstract = {

The transition of intrinsically disordered, monomeric α-synuclein into β-sheet-rich oligomers and fibrils is associated with multiple neurodegenerative diseases. Fibrillar aggregates possessing distinct structures that differ in their toxicity, have been observed in different pathological phenotypes. Understanding the mechanism of formation of various fibril polymorphs with differing cytotoxic effects, is essential for determining how the aggregation reaction could be modulated to favor non-toxic fibrils over toxic fibrils. In this study, two morphologically different α-synuclein fibrils, one helical and the other ribbon-like, are shown to form together. Surprisingly, a widely-used small molecule for probing aggregation reactions, thioflavin T (ThT), is found to tune the structural heterogeneity found in the fibrils. The ribbon-like fibrils formed in the presence of ThT are found to have a longer structural core than do the helical fibrils formed in the absence of ThT. The ribbon-like fibrils are also more toxic to cells. By facilitating the formation of ribbon-like fibrils over helical fibrils, ThT reduces the extent of fibril polymorphism. This study highlights the role of a small molecule such as ThT in selectively favoring the formation of a specific type of fibril, by binding to aggregates formed early on one of multiple pathways, thereby altering the structural core and external morphology of the fibrils formed.

}, issn = {1083-351X}, doi = {10.1074/jbc.M117.795617}, author = {Kumar, Harish and Singh, Jogender and Kumari, Pratibha and Udgaonkar, Jayant B} } @article {24294, title = {Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region.}, journal = {Proc Natl Acad Sci U S A}, year = {2017}, month = {2017 Oct 02}, abstract = {

Point mutations in genes encoding sarcomeric proteins are the leading cause of inherited primary cardiomyopathies. Among them are mutations in the TNNT2 gene that encodes cardiac troponin T (TnT). These mutations are clustered in the tropomyosin (Tm) binding region of TnT, TNT1 (residues 80-180). To understand the mechanistic changes caused by pathogenic mutations in the TNT1 region, six hypertrophic cardiomyopathy (HCM) and two dilated cardiomyopathy (DCM) mutants were studied by biochemical approaches. Binding assays in the absence and presence of actin revealed changes in the affinity of some, but not all, TnT mutants for Tm relative to WT TnT. HCM mutants were hypersensitive and DCM mutants were hyposensitive to Ca(2+) in regulated actomyosin ATPase activities. To gain better insight into the disease mechanism, we modeled the structure of TNT1 and its interactions with Tm. The stability predictions made by the model correlated well with the affinity changes observed in vitro of TnT mutants for Tm. The changes in Ca(2+) sensitivity showed a strong correlation with the changes in binding affinity. We suggest the primary reason by which these TNNT2 mutations between residues 92 and 144 cause cardiomyopathy is by changing the affinity of TnT for Tm within the TNT1 region.

}, issn = {1091-6490}, doi = {10.1073/pnas.1710354114}, author = {Gangadharan, Binnu and Sunitha, Margaret S and Mukherjee, Souhrid and Chowdhury, Ritu Roy and Haque, Farah and Sekar, Narendrakumar and Sowdhamini, Ramanathan and Spudich, James A and Mercer, John A} } @article {13638, title = {Motor control of Drosophila feeding behavior.}, journal = {Elife}, volume = {6}, year = {2017}, month = {2017 Feb 17}, abstract = {

The precise coordination of body parts is essential for survival and behavior of higher organisms. While progress has been made towards the identification of central mechanisms coordinating limb movement, only limited knowledge exists regarding the generation and execution of sequential motor action patterns at the level of individual motoneurons. Here we use Drosophila proboscis extension as a model system for a reaching-like behavior. We first provide a neuroanatomical description of the motoneurons and muscles contributing to proboscis motion. Using genetic targeting in combination with artificial activation and silencing assays we identify the individual motoneurons controlling the five major sequential steps of proboscis extension and retraction. Activity-manipulations during naturally evoked proboscis extension show that orchestration of serial motoneuron activation does not rely on feed-forward mechanisms. Our data support a model in which central command circuits recruit individual motoneurons to generate task-specific proboscis extension sequences.

}, issn = {2050-084X}, doi = {10.7554/eLife.19892}, author = {Schwarz, Olivia and Bohra, Ali Asgar and Liu, Xinyu and Reichert, Heinrich and VijayRaghavan, Krishnaswamy and Pielage, Jan} } @article {15639, title = {Multirate method for co-simulation of electrical-chemical systems in multiscale modeling.}, journal = {J Comput Neurosci}, year = {2017}, month = {2017 Apr 07}, abstract = {

Multiscale modeling by means of co-simulation is a powerful tool to address many vital questions in neuroscience. It can for example be applied in the study of the process of learning and memory formation in the brain. At the same time the co-simulation technique makes it possible to take advantage of interoperability between existing tools and multi-physics models as well as distributed computing. However, the theoretical basis for multiscale modeling is not sufficiently understood. There is, for example, a need of efficient and accurate numerical methods for time integration. When time constants of model components are different by several orders of magnitude, individual dynamics and mathematical definitions of each component all together impose stability, accuracy and efficiency challenges for the time integrator. Following our numerical investigations in Brocke et al. (Frontiers in Computational Neuroscience, 10, 97, 2016), we present a new multirate algorithm that allows us to handle each component of a large system with a step size appropriate to its time scale. We take care of error estimates in a recursive manner allowing individual components to follow their discretization time course while keeping numerical error within acceptable bounds. The method is developed with an ultimate goal of minimizing the communication between the components. Thus it is especially suitable for co-simulations. Our preliminary results support our confidence that the multirate approach can be used in the class of problems we are interested in. We show that the dynamics ofa communication signal as well as an appropriate choice of the discretization order between system components may have a significant impact on the accuracy of the coupled simulation. Although, the ideas presented in the paper have only been tested on a single model, it is likely that they can be applied to other problems without loss of generality. We believe that this work may significantly contribute to the establishment of a firm theoretical basis and to the development of an efficient computational framework for multiscale modeling and simulations.

}, issn = {1573-6873}, doi = {10.1007/s10827-017-0639-7}, author = {Brocke, Ekaterina and Djurfeldt, Mikael and Bhalla, Upinder S and Kotaleski, Jeanette Hellgren and Hanke, Michael} } @article {15479, title = {The mystery of membrane organization: composition, regulation and roles of lipid rafts.}, journal = {Nat Rev Mol Cell Biol}, year = {2017}, month = {2017 Mar 30}, abstract = {

Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A large number of studies have focused on understanding the basis for this heterogeneity and its physiological relevance. The membrane raft hypothesis formalized a physicochemical principle for a subtype of such lateral membrane heterogeneity, in which the preferential associations between cholesterol and saturated lipids drive the formation of relatively packed (or ordered) membrane domains that selectively recruit certain lipids and proteins. Recent studies have yielded new insights into this mechanism and its relevance in vivo, owing primarily to the development of improved biochemical and biophysical technologies.

}, issn = {1471-0080}, doi = {10.1038/nrm.2017.16}, author = {Sezgin, Erdinc and Levental, Ilya and Mayor, Satyajit and Eggeling, Christian} } @article {17526, title = {New Frontiers for Chemical Ecology: Reaffirming a Commitment to the G{\"o}teborg Resolution : Guest Editorial: *The Bengaluru Consortium.}, journal = {J Chem Ecol}, volume = {43}, year = {2017}, month = {2017 Jan}, pages = {2-3}, issn = {1573-1561}, doi = {10.1007/s10886-016-0813-9}, author = {Olsson, Shannon B} } @article {24896, title = {A new large species of gecko of the genus Hemidactylus Oken, 1817 (Reptilia: Sauria: Gekkonidae) from the Eastern Ghats, India.}, journal = {C R Biol}, year = {2017}, month = {2017 Oct 13}, abstract = {

A new large species of gecko superficially resembling Hemidactylus maculatus Dum{\'e}ril \& Bibron and its allied large Hemidactylus is described from Eastern Ghats. The new species, Hemidactylus kangerensis sp. nov. can be easily distinguished from members of the H.\ maculatus complex based on the number of femoral pores, i.e. 18-21 on each side, separated medially by 4\ non-pored scales. A phylogenetic analysis based on partial sequence of mitochondrial gene cytochrome b shows that the gecko is a member of the "H.\ prashadi" clade and is sister to H.\ maculatus, from which it differs in an uncorrected pairwise sequence divergence of 10\%. The discovery of a new large gecko from Eastern Ghats advocates the need for biodiversity assessment across the neglected Eastern Ghats.

}, issn = {1768-3238}, doi = {10.1016/j.crvi.2017.09.003}, author = {Mirza, Zeeshan A and Bhosale, Harshal and Patil, Rishikesh} } @article {27667, title = {A new species of large-bodied, tuberculate Hemidactylus Oken~(Squamata: Gekkonidae) from the Eastern Ghats, India.}, journal = {Zootaxa}, volume = {4347}, year = {2017}, month = {2017 Nov 13}, pages = {331-345}, abstract = {

A distinct new gecko of the genus Hemidactylus is described from Andhra Pradesh, India. This large-sized (snout to vent length up to at least 105 mm), scansorial Hemidactylus is characterized by dorsal scalation of small granules intermixed with large, pointed, trihedral tubercles that form 16-17 fairly regularly arranged longitudinal rows at midbody; 9-11 subdigital lamellae below the first and 11-13 below the fourth digit; 6-8 strongly pointed and keeled enlarged tubercles on the original tail; 20-23 femoral pores separated by 4 poreless scales in males; 11-13 supralabials and 9-11 infralabials. This is the third vertebrate endemic to the Mahendragiri Range, highlighting the significance of this topographically complex region.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4347.2.8}, author = {Giri, Varad B and Bauer, Aaron M and Mohapatra, Pratyush P and Srinivasulu, Chelmala and Agarwal, Ishan} } @article {25709, title = {A new species of Platypleura Amyot \& Audinet-Serville, 1843 (Hemiptera: Cicadidae: Cicadinae) from the Eastern Ghats of Andhra Pradesh, India}, journal = {Zootaxa}, volume = {4311}, year = {2017}, month = {08/2017}, pages = {523-536}, abstract = {

We here describe a new cicada species, Platypleura poorvachala sp. nov., (Hemiptera: Cicadidae: Cicadinae) from the Eastern Ghats of India. The combination of following characters distinguishes this species from its platypleurine relatives: (a) transverse continuous infuscation along the nodal line and in the central area of the forewings, and (b) opaque hindwings, which are indochine-coloured with two prominent sub-distal black bands. We illustrate the male and female types and the male genitalia, and present a photographic plate for comparison of this species with other Indian and Southeast Asian Platypleura species with respect to its morphology and distribution.

}, doi = {10.11646/zootaxa.4311.4.5}, author = {Marathe, Kiran and Yeshwanth, HM and Basu, DN and Kunte, Krushnamegh} } @article {25693, title = {A new species of Rhabdops Boulenger, 1893 (Serpentes: Natricinae) from the northern Western Ghats region of India}, journal = {Zootaxa}, volume = {4319}, year = {2017}, month = {09/2017}, pages = {27-52}, abstract = {

Based on analyses of new DNA sequence data for two nuclear (rag1, cmos) and three mitochondrial (16s, cytb, nd4) genes, the Indian snake genus Rhabdops is a natricine. Variation in geography, DNA sequences, the number of ventral scales, pattern and colour for samples of Rhabdops from along the Western Ghats region of peninsular India is concordant, discontinuous and bimodal. We recognise populations from the northern Western Ghats as distinct specifically from the more southerly R. olivaceus and describe Rhabdops aquaticus sp. nov. based on a series of eight specimens from two localities in the Northern Western Ghats. Rhabdops aquaticus sp. nov. is associated particularly with upland laterite plateaus and their associated streams, a threatened habitat within its known distribution.

}, doi = {10.11646/zootaxa.4319.1.2}, author = {Giri, Varad B and Deepak, V. and Captain, Ashok and Das, Abhijit and Das, Sandeep and Rajkumar, KP and Rathish, RL and Gower, David J.} } @article {28260, title = {A new species of Theretra Hubner (Lepidoptera: Sphingidae) from the southern Western Ghats, India}, journal = {ZOOTAXA}, volume = {4323}, year = {2017}, month = {09/2017}, pages = {185-196}, abstract = {

A new species of the genus Theretra Hubner [1819], Theretra shendurneensis sp. nov., is described from Shendurney Wildlife Sanctuary, southern Western Ghats, India, based on external and internal morphology, and genetic markers. The new species is compared in external and male genital morphology, genetic divergence and geographic range with three similar and closely related species: T. boisduvalii (Bugnion, 1839), T. sumatrensis (Joicey and Kaye, 1917) and T. rhesus (Boisduval, [1875]). Recent changes to the classification of Theretra are discussed and rejected.

}, doi = {10.11646/zootaxa.4323.2.2}, author = {Sondhi, Yash and Kitching, Ian J. and Basu, Dipendra Nath and Kunte, Krushnamegh} } @article {26654, title = {A new subspecies of large-eared pika, Ochotona macrotis (Lagomorpha: Ochotonidae), from the Eastern Himalaya}, journal = {Russian J. Theriol}, volume = {16}, year = {2017}, month = {2017}, pages = {30{\textendash}42}, abstract = {

We examined 212 complete sequences of the cytochrome b gene for all pika species
(Lagomorpha: Ochotona) as well as 250 skulls of pikas from the eastern Himalayan region. The results of
our analyses suggest that a new and distinct subspecies of large-eared pika {\textemdash} Ochotona macrotis gomchee
ssp.n. occurs in Bhutan. Our phylogenetic analyses indicate that this subspecies holds a sister-taxon
relationship to other O. macrotis. The cranial shape of O. m. gomchee ssp.n. is similar to that of remaining
O. macrotis; pelage colouration and ear length differentiate O. m. gomchee ssp.n. from all other representatives
of O. macrotis. We hypothesize that pikas from the Great Bend of the Tsangpo River, which were
previously assigned to O. forresti, in fact belong to O. macrotis; the correct name for that particular
subspecies is therefore amended to O. m. duoxionglaensis. The distributional ranges of O. m. gomchee
ssp.n. and O. m. duoxionglaensis are hypothesized to be separated by a broad matrix of unsuitable habitats.
How to cite this article: Lissovsky A.A., McDonough M., Dahal N., Jin Wei, Liu Shaoying, Ruedas L.A.
2017. A new subspecies of large-eared pika, Ochotona macrotis (Lagomorpha: Ochotonidae), from the
Eastern Himalaya // Russian J. Theriol. Vol.16. No.1. P.30{\textendash}42. doi: 10.15298/rusjtheriol.16.1.03

}, doi = {10.15298/rusjtheriol.16.1.03}, author = {Lissovsky, Andrey A and McDonough, M and Dahal, Nishma and Jin, W and Liu, S and Ruedas, LA} } @article {26575, title = {Non-sister Sri Lankan white-eyes (genus Zosterops) are a result of independent colonizations.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0181441}, abstract = {

Co-occurrence of closely related taxa on islands could be attributed to sympatric speciation or multiple colonization. Sympatric speciation is considered to be rare in small islands, however multiple colonizations are known to be common in both oceanic and continental islands. In this study we investigated the phylogenetic relatedness and means of origin of the two sympatrically co-occurring Zosterops white-eyes, the endemic Zosterops ceylonensis and its widespread regional congener Z. palpebrosus, in the island of Sri Lanka. Sri Lanka is a continental island in the Indian continental shelf of the Northern Indian Ocean. Our multivariate morphometric analyses confirmed the phenotypic distinctness of the two species. Maximum Likelihood and Bayesian phylogenetic analyses with ~2000bp from two mitochondrial (ND2 and ND3) and one nuclear (TGF) gene indicated that they are phylogenetically distinct, and not sister to each other. The two subspecies of the peninsula India; Z. p. egregius of Sri Lanka and India and Z. p. nilgiriensis of Western Ghats (India) clustered within the Z. palpebrosus clade having a common ancestor. In contrast, the divergence of the endemic Z. ceylonensis appears to be much deeper and is basal to the other Zosterops white-eyes. Therefore we conclude that the two Zosterops species originated in the island through independent colonizations from different ancestral lineages, and not through island speciation or multiple colonization from the same continental ancestral population. Despite high endemism, Sri Lankan biodiversity is long considered to be a subset of southern India. This study on a speciose group with high dispersal ability and rapid diversification rate provide evidence for the contribution of multiple colonizations in shaping Sri Lanka{\textquoteright}s biodiversity. It also highlights the complex biogeographic patterns of the South Asian region, reflected even in highly vagile groups such as birds.

}, keywords = {Animals, Bayes Theorem, Biodiversity, DNA, Mitochondrial, Evolution, Molecular, Genetic Speciation, Geography, Passeriformes, Phylogeny, Sri Lanka, Sympatry}, issn = {1932-6203}, doi = {10.1371/journal.pone.0181441}, author = {Wickramasinghe, Nelum and Robin, V V and Ramakrishnan, Uma and Reddy, Sushma and Seneviratne, Sampath S} } @article {22811, title = {Nucleoid-Associated Proteins: Genome Level Occupancy and Expression Analysis.}, journal = {Methods Mol Biol}, volume = {1624}, year = {2017}, month = {2017}, pages = {85-97}, abstract = {

The advent of Chromatin Immunoprecipitation sequencing (ChIP-Seq) has allowed the identification of genomic regions bound by a DNA binding protein in-vivo on a genome-wide scale. The impact of the DNA binding protein on gene expression can be addressed using transcriptome experiments in appropriate genetic settings. Overlaying the above two sources of data enables us to dissect the direct and indirect effects of a DNA binding protein on gene expression. Application of these techniques to Nucleoid Associated Proteins (NAPs) and Global Transcription Factors (GTFs) has underscored the complex relationship between DNA-protein interactions and gene expression change, highlighting the role of combinatorial control. Here, we demonstrate the usage of ChIP-Seq to infer binding properties and transcriptional effects of NAPs such as Fis and HNS, and the GTF CRP in the model organism Escherichia coli K12 MG1655 (E. coli).

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-7098-8_8}, author = {Singh, Parul and Seshasayee, Aswin Sai Narain} } @article {26284, title = {Octopamine Drives Endurance Exercise Adaptations in Drosophila.}, journal = {Cell Rep}, volume = {21}, year = {2017}, month = {2017 Nov 14}, pages = {1809-1823}, abstract = {

Endurance exercise is an effective therapeutic intervention with substantial pro-healthspan effects. Male Drosophila respond to a ramped daily program of exercise by inducing conserved physiological responses similar to those seen in mice and humans. Female flies respond to an exercise stimulus but do\ not experience the adaptive training response seen in males. Here, we use female flies as a model\ to demonstrate that differences in exercise response are mediated by differences in neuronal activity. The activity of octopaminergic neurons is specifically required to induce the conserved cellular and physiological changes seen following endurance training. Furthermore, either intermittent, scheduled activation of octopaminergic neurons or octopamine feeding is able to fully substitute for exercise, conferring a suite of pro-healthspan benefits to sedentary Drosophila. These experiments indicate that octopamine is a critical mediator of adaptation to endurance exercise in Drosophila.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2017.10.065}, author = {Sujkowski, Alyson and Ramesh, Divya and Brockmann, Axel and Wessells, Robert} } @article {28247, title = {Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Dec 11}, pages = {17289}, abstract = {

Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increased in human cervical cancer (CxCa) tissues and tumour-infiltrating Treg cells (CD4+CD25hiCD127low), whereas blocking ERα with the antagonist ICI 182,780 abolishes FOXP3 expression and impairs the function of CxCa infiltrating Treg cells. Using a novel approach of co-immunoprecipitation with antibodies to E2 for capture, we identified binding of E2:ERα complexes to FOXP3 protein in CxCa-derived Treg cells. Chromatin immunoprecipitation analyses of male blood Treg cells revealed ERα occupancy at the FOXP3 promoter and conserved non-coding DNA elements 2 and 3. Accordingly, computational analyses of the enriched regions uncovered eight putative oestrogen response elements predicted to form a loop that can activate the FOXP3 promoter. Together, these data suggest that E2-mediated ERα signalling is critical for the sustenance of FOXP3 expression and Treg cell function in human CxCa via direct interaction of ERα with FOXP3 promoter. Overall, our work gives a molecular insight into ERα signalling and highlights a fundamental role of E2 in controlling human Treg cell physiology.

}, issn = {2045-2322}, doi = {10.1038/s41598-017-17102-w}, author = {Adurthi, Sreenivas and Kumar, Mahesh M and Vinodkumar, H S and Mukherjee, Geetashree and Krishnamurthy, H and Acharya, K Kshitish and Bafna, U D and Uma, Devi K and Abhishekh, B and Krishna, Sudhir and Parchure, A and Alka, Murali and Jayshree, R S} } @article {25258, title = {Organelle acidification: an ancient cellular leak detector.}, journal = {BMC Biol}, volume = {15}, year = {2017}, month = {2017 Jun 26}, pages = {51}, abstract = {

Intracellular membrane-bounded organelles of eukaryotic cells transiently contact the extracellular environment during endocytosis and secretion. Such contacts must be precisely timed to prevent leakage of cargo. I argue that early eukaryotes evolved organelle acidification as a way to detect and prevent leakage.

}, issn = {1741-7007}, doi = {10.1186/s12915-017-0395-1}, author = {Thattai, Mukund} } @article {14979, title = {Packing energetics determine the folding routes of the RNase-H proteins.}, journal = {Phys Chem Chem Phys}, year = {2017}, month = {2017 Mar 20}, abstract = {

Comparative studies of proteins from a family have been used to understand the factors that determine the folding routes of proteins. It has been conjectured that the folding mechanism of ribonuclease-H (RNase-H) proteins is determined by the topology of their fold. To test this hypothesis, we computationally studied the folding of four proteins from the RNase-H family, which have the overall RNase-H fold, but whose topologies differ in the region termed CORE in E. coli RNase-H. We simulated the folding of these proteins using molecular dynamics (MD) simulations of a coarse-grained structure-based model (SBM) which captures the effects of topology and found that the four proteins had similar folding routes. However, these simulated folding routes do not agree with the folding routes of those RNase-H proteins that have been experimentally characterized. We next simulated the proteins using an SBM which specifically accounts for packing energetics and found that these routes not only vary substantially across the simulated RNase-H proteins but also agree with experiments. Thus, the packing energetics determine the folding mechanism of the RNase-H proteins. By comparing the differing folding routes calculated from the two models, we isolated packing interactions that promote these differences. We find that the balance of packing energetics between CORE and the rest of the protein is different across the different RNase-Hs. This balance determines the folding route. Our studies suggest that proteins from the RNase-H family should be used for experimentally detecting structurally distinct folding routes.

}, issn = {1463-9084}, doi = {10.1039/c6cp08940b}, author = {Yadahalli, Shilpa and Gosavi, Shachi} } @article {20327, title = {Pharyngeal stimulation with sugar triggers local searching behavior in Drosophila.}, journal = {J Exp Biol}, year = {2017}, month = {2017 Jul 06}, abstract = {

Foraging behavior is essential for all organisms to find food containing nutritional chemicals. A hungry fly of Drosophila melanogaster performs local searching behavior after drinking a small amount of sugar solution. Using video tracking we examined how the searching behavior is regulated in D. melanogaster We found that a small amount of highly concentrated sugar solution induced a long-lasting searching behavior. After the intake of sugar solution, a fly moved around in circles and repeatedly returned to the position where the sugar droplet had been placed. The non-nutritious sugar, D-arabinose, but not the non-sweet nutritious sugar, D-sorbitol, was effective in inducing the behavior, indicating that sweet sensation is essential. Furthermore, pox-neuro mutant flies with no external taste bristles showed local searching behavior, suggesting the involvement of the pharyngeal taste organ. Experimental activation of pharyngeal sugar-sensitive gustatory receptor neurons by capsaicin using the Gal4/UAS system induced local searching behavior. In contrast, inhibition of pharyngeal sugar-responsive gustatory receptor neurons abolished the searching behavior. Together our results indicate that in Drosophila the pharyngeal taste-receptor neurons trigger searching behavior immediately after ingestion.

}, issn = {1477-9145}, doi = {10.1242/jeb.161646}, author = {Murata, Satoshi and Brockmann, Axel and Tanimura, Teiichi} } @article {17518, title = {Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics during clathrin-mediated endocytosis.}, journal = {J Cell Sci}, year = {2017}, month = {2017 May 15}, abstract = {

Endocytic turnover is essential to regulate the protein composition and function of the plasma membrane thus regulating the plasma membrane levels of many receptors. In Drosophila photoreceptors, photon absorption by the GPCR rhodopsin 1 (Rh1) triggers its endocytosis by clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5 compartment. The Rh1 trafficking defect in dPIP4K-depleted cells could be suppressed by downregulating Rab5 function or by selectively reconstituting dPIP4K in the PI3P enriched early endosomal (EE) compartment of photoreceptors. We also found that loss of PIP4K was associated with increased CME and an enlarged Rab5 compartment in cultured Drosophila cells. Collectively our findings define PIP4K as a novel regulator of early endosomal homeostasis during CME.

}, issn = {1477-9137}, doi = {10.1242/jcs.202259}, author = {Kamalesh, Kumari and Trivedi, Deepti and Toscano, Sarah and Sharma, Sanjeev and Kolay, Sourav and Raghu, Padinjat} } @article {25698, title = {A phylogeny of open-habitat lizards (Squamata: Lacertidae: Ophisops) supports the antiquity of Indian grassy biomes}, journal = {JOURNAL OF BIOGEOGRAPHY }, volume = {44}, year = {2017}, month = {09/2017}, pages = {2021-2032}, abstract = {

India is dominated by tropical grassy biomes (TGBs), traditionally considered seres or degraded forest, with low diversity relative to the restricted, ancestral wet zone. It is unclear if Indian grasslands and other open habitats are anthropogenically derived or native, old-growth habitats; without a clear timescale of grassland evolution. One way to understand grassland evolution is to study the diversification in taxa restricted to open habitats. We use a dated phylogeny of Ophisops to address questions related to the origin, diversification and inter-relationships of Indian and Saharo-Arabian Ophisops, and ultimately the origin of Indian grasslands and open habitats.

}, doi = {10.1111/jbi.12999}, author = {Agarwal, Ishan and Ramakrishnan, Uma} } @article {28258, title = {Populations and activity patterns of clouded leopards and marbled cats in Dampa Tiger Reserve, India}, journal = {JOURNAL OF MAMMALOGY}, volume = {98}, year = {2017}, month = {10/2017}, pages = {1453-1462}, abstract = {

The rapidly declining tropical forests of Asia support a diversity of felid species, many of which are rare and little known. We used camera traps in Dampa Tiger Reserve (TR), Mizoram, northeastern India, to estimate population density and describe activity patterns of 2 rare felids, the clouded leopard (Neofelis nebulosa) and marbled cat (Pardofelis marmorata). With a survey effort of 4,962 trap nights, we obtained 84 photo-captures of clouded leopards and 36 of marbled cats. We used spatially explicit capture-recapture methods to estimate population densities of both species. Using the Bayesian approach implemented in SPACECAP, we derived estimates of 5.14 (+/- 1.80 SD)/100 km(2) for clouded leopards and 5.03 (+/- 2.07 SD)/100 km(2) for marbled cats. Using camera-trap images, we compared diel activity patterns and activity overlaps for these 2 rare felids, together with 3 other sympatric carnivores, by estimating a coefficient of overlap between species. Among felids, clouded leopards and golden cats (Catopuma temminckii) displayed the highest overlap in activity, whereas marbled cats and leopard cats (Prionailurus bengalensis) showed the lowest, with marbled cats being primarily diurnal and leopard cats nocturnal. Our study provides the first density estimates from continental Southeast Asia for marbled cats and one of the highest recorded densities for clouded leopards. These results are of special significance since Dampa sustains an ecosystem that has in recent times undergone near extirpation of large predators.

}, doi = {10.1093/jmammal/gyx104}, author = {Singh, Priya and Macdonald, David W.} } @article {20956, title = {Protein-protein interfaces are vdW dominant with selective H-bonds and (or) electrostatics towards broad functional specificity.}, journal = {Bioinformation}, volume = {13}, year = {2017}, month = {2017}, pages = {164-173}, abstract = {

Several catalysis, cellular regulation, immune function, cell wall assembly, transport, signaling and inhibition occur through Protein- Protein Interactions (PPI). This is possible with the formation of specific yet stable protein-protein interfaces. Therefore, it is of interest to understand its molecular principles using structural data in relation to known function. Several interface features have been documented using known X-ray structures of protein complexes since 1975. This has improved our understanding of the interface using structural features such as interface area, binding energy, hydrophobicity, relative hydrophobicity, salt bridges and hydrogen bonds. The strength of binding between two proteins is dependent on interface size (number of residues at the interface) and thus its corresponding interface area. It is known that large interfaces have high binding energy (sum of (van der Waals) vdW, H-bonds, electrostatics). However, the selective role played by each of these energy components and more especially that of vdW is not explicitly known. Therefore, it is important to document their individual role in known protein-protein structural complexes. It is of interest to relate interface size with vdW, H-bonds and electrostatic interactions at the interfaces of protein structural complexes with known function using statistical and multiple linear regression analysis methods to identify the prominent force. We used the manually curated non-redundant dataset of 278 hetero-dimeric protein structural complexes grouped using known functions by Sowmya et al. (2015) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (Anshul and Sowdhamini, 2015). This dataset consists of obligatory (enzymes, regulator, biological assembly), immune and nonobligatory (enzyme and regulator inhibitors) complexes. Results show that the total binding energy is more for large interfaces. However, this is not true for its individual energy factors. Analysis shows that vdW energies contribute to about 75\% {\textpm} 11\% on average among all complexes and it also increases with interface size (r2 ranging from 0.67 to 0.89 with p\<0.01) at 95\% confidence limit irrespective of molecular function. Thus, vdW is both dominant and proportional at the interface independent of molecular function. Nevertheless, H bond energy contributes to 15\% {\textpm} 6.5\% on average in these complexes. It also moderately increases with interface size (r2 ranging from 0.43 to 0.61 with p\<0.01) only among obligatory and immune complexes. Moreover, there is about 11.3\% {\textpm} 8.7\% contribution by electrostatic energy. It increases with interface size specifically among non-obligatory regulator-inhibitors (r2 = 0.44). It is implied that both H-bonds and electrostatics are neither dominant nor proportional at the interface. Nonetheless, their presence cannot be ignored in binding. Therefore, H-bonds and (or) electrostatic energy having specific role for improved stability in complexes is implied. Thus, vdW is common at the interface stabilized further with selective H-bonds and (or) electrostatic interactions at an atomic level in almost all complexes. Comparison of this observation with residue level analysis of the interface is compelling. The role by H-bonds (14.83\% {\textpm} 6.5\% and r2 = 0.61 with p\<0.01) among obligatory and electrostatic energy (8.8\% {\textpm} 4.77\% and r2 = 0.63 with p \<0.01) among non-obligatory complexes within interfaces (class A) having more non-polar residues than surface is influencing our inference. However, interfaces (class B) having less non-polar residues than surface show 1.5 fold more electrostatic energy on average. The interpretation of the interface using inter-atomic (vdW, H-bonds, electrostatic) interactions combined with inter-residue predominance (class A and class B) in relation to known function is the key to reveal its molecular principles with new challenges.

}, issn = {0973-2063}, doi = {10.6026/97320630013164}, author = {Nilofer, Christina and Sukhwal, Anshul and Mohanapriya, Arumugam and Kangueane, Pandjassarame} } @article {13641, title = {A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 Feb 14}, pages = {42586}, abstract = {

Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation.

}, issn = {2045-2322}, doi = {10.1038/srep42586}, author = {Richhariya, Shlesha and Jayakumar, Siddharth and Abruzzi, Katharine and Rosbash, Michael and Hasan, Gaiti} } @article {28067, title = {Ral function in muscle is required for flight maintenance in Drosophila.}, journal = {Small GTPases}, year = {2017}, month = {2017 Dec 28}, pages = {1-6}, abstract = {

Ral is a small GTPase of the Ras superfamily that is important for a number of cellular functions. Recently, we found that expression of Ral is regulated by store-operated calcium entry (SOCE) in Drosophila neurons. In this study, through genetic and behavioural experiments, we show that Ral function is required in differentiated muscles for flight. Reducing Ral function in muscles, specifically reduced duration of flight bouts but not other motor functions, like climbing. Interestingly, unlike in the nervous system, Ral expression in the muscle is not regulated by SOCE. Moreover, either knockdown or genetic inhibition of SOCE in muscles does not affect flight. These findings demonstrate that a multiplicity of signalling mechanisms very likely regulate Ral expression in different tissues.

}, issn = {2154-1256}, doi = {10.1080/21541248.2017.1367456}, author = {Richhariya, Shlesha and Hasan, Gaiti} } @article {25696, title = {On the recent designation of a neotype for the taxon Calotes versicolor (Daudin, 1802) (Reptilia: Agamidae)}, journal = {Zootaxa}, volume = {4317}, year = {2017}, month = {09/2017}, pages = {585-587}, abstract = {

Calotes versicolor (Daudin, 1802) is a widespread species of agamid lizard found commonly in the Indian subcontinent and the Indo-Chinese region with a complicated taxonomic history (Uetz \& Hosek, 2016). The type locality of this species has been debatable (Smith, 1935, Amarasinghe et al. 2009) and the recent designation of a neotype from Pondicherry by Gowande et al. (2016) though much warranted, introduces additional complications that impede a thorough taxonomic resolution of this species complex.

}, doi = {10.11646/zootaxa.4317.3.10}, author = {Chaitanya, R and Giri, Varad B and Deepak, V.} } @article {157124, title = {Regulation of Plant microRNA Biogenesis}, year = {2017}, abstract = {

Micro (mi)RNAs are small regulatory RNA molecules involved in post-transcriptional silencing of their target mRNAs. In plants, these miRNAs target mRNAs coding for transcription factors and key regulators, thus modulating plant development, defence, and metabolic processes. miRNAs mostly originate from MIR genes that are transcribed to long primary (pri)miRNA transcripts by Pol II. These pri-miRNA transcripts fold-back to give rise to specific stem-loop structures that are cleaved by Dicer-like (DCL) proteins to Pre-miRNA intermediates. Pre-miRNAs are precisely processed into mature miRNA/miRNA* duplex of 20-22-nt length by DCL1 with the help of few accessory proteins. It is not known why only one or rarely more than one miRNA results from these long dsRNA precursors. In this review, we discuss recent studies including our unpublished work on structural and sequence determinants of plant miRNAs that distinguish them from their precursor regions. These determinants play a major role in accurate and precise dicing of miRNAs from their precursors, thus contributing to abundance and stability of mature miRNAs.

}, doi = {10.16943/ptinsa/2017/49237}, url = {https://www.researchgate.net/publication/321099725_Regulation_of_Plant_miRNA_Biogenesis}, author = {Anushree Narjala and PV Shivaprasad} } @article {157119, title = {Regulation of Plant miRNA Biogenesis}, year = {2017}, abstract = {

Micro (mi)RNAs are small regulatory RNA molecules involved in post-transcriptional silencing of their target mRNAs. In plants, these miRNAs target mRNAs coding for transcription factors and key regulators, thus modulating plant development, defence, and metabolic processes. miRNAs mostly originate from MIR genes that are transcribed to long primary (pri)miRNA transcripts by Pol II. These pri-miRNA transcripts fold-back to give rise to specific stem-loop structures that are cleaved by Dicer-like (DCL) proteins to Pre-miRNA intermediates. Pre-miRNAs are precisely processed into mature miRNA/miRNA* duplex of 20-22-nt length by DCL1 with the help of few accessory proteins. It is not known why only one or rarely more than one miRNA results from these long dsRNA precursors. In this review, we discuss recent studies including our unpublished work on structural and sequence determinants of plant miRNAs that distinguish them from their precursor regions. These determinants play a major role in accurate and precise dicing of miRNAs from their precursors, thus contributing to abundance and stability of mature miRNAs.

}, doi = {10.16943/ptinsa/2017/49237}, url = {https://www.researchgate.net/publication/321099725_Regulation_of_Plant_miRNA_Biogenesis}, author = {Anushree Narjala and PV Shivaprasad} } @article {27276, title = {Repression of YdaS Toxin Is Mediated by Transcriptional Repressor RacR in the Cryptic rac Prophage of Escherichia coli K-12.}, journal = {mSphere}, volume = {2}, year = {2017}, month = {2017 Nov-Dec}, abstract = {

Horizontal gene transfer is a major driving force behind the genomic diversity seen in prokaryotes. The cryptic rac prophage in Escherichia\ coli K-12 carries the gene for a putative transcription factor RacR, whose deletion is lethal. We have shown that the essentiality of racR in E.\ coli K-12 is attributed to its role in transcriptionally repressing toxin gene(s) called ydaS and ydaT, which are adjacent to and coded divergently to racR. IMPORTANCE Transcription factors in the bacterium E.\ coli are rarely essential, and when they are essential, they are largely toxin-antitoxin systems. While studying transcription factors encoded in horizontally acquired regions in E.\ coli, we realized that the protein RacR, a putative transcription factor encoded by a gene on the rac prophage, is an essential protein. Here, using genetics, biochemistry, and bioinformatics, we show that its essentiality derives from its role as a transcriptional repressor of the ydaS and ydaT genes, whose products are toxic to the cell. Unlike type II toxin-antitoxin systems in which transcriptional regulation involves complexes of the toxin and antitoxin, repression by RacR is sufficient to keep ydaS transcriptionally silent.

}, issn = {2379-5042}, doi = {10.1128/mSphere.00392-17}, author = {Krishnamurthi, Revathy and Ghosh, Swagatha and Khedkar, Supriya and Seshasayee, Aswin Sai Narain} } @article {19200, title = {The road not taken: Could stress-specific mutations lead to different evolutionary paths?}, journal = {PLoS Biol}, volume = {15}, year = {2017}, month = {2017 Jun}, pages = {e2002862}, abstract = {

Organisms often encounter stressful conditions, some of which damage their DNA. In response, some organisms show a high expression of error-prone DNA repair machinery, causing a temporary increase in the genome-wide mutation rate. Although we now have a detailed map of the molecular mechanisms underlying such stress-induced mutagenesis (SIM), it has been hotly debated whether SIM alters evolutionary dynamics. Key to this controversy is our poor understanding about which stresses increase mutagenesis and their long-term consequences for adaptation. In a new study with Escherichia coli, Maharjan and Ferenci show that while only some nutritional stresses (phosphorous and carbon limitation) increase total mutation rates, each stress generates a unique spectrum of mutations. Their results suggest the potential for specific stresses to shape evolutionary dynamics and highlight the necessity for explicit tests of the long-term evolutionary impacts of SIM.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.2002862}, author = {Agashe, Deepa} } @article {17517, title = {Salt-mediated oligomerization of the mouse prion protein monitored by real time NMR.}, journal = {J Mol Biol}, year = {2017}, month = {2017 May 11}, abstract = {

The prion protein forms {\ss}-rich soluble oligomers in vitro at pH4 in the presence of physiological concentrations of salt. In the absence of salt, oligomerization and misfolding does not take place in an experimentally tractable timescale. While it is well established that a lowering of pH facilitates misfolding and oligomerization of this protein, the role of salt remains poorly understood. Here, solution-state NMR was used to probe perturbations in the monomeric mouse prion protein moPrP) structure immediately upon salt-addition, prior to the commencement of the oligomerization reaction. The weak binding of salt at multiple sites dispersed all over the monomeric protein causes a weak non-specific perturbation of structure throughout the protein. The only significant perturbation occurs in the loop between helix 2 and 3 in and around the partially buried K193-E195 salt bridge. The disruption of this key electrostatic interaction is the earliest detectable change in the monomer before any major conformational change occurs and appears to constitute the trigger for the commencement of misfolding and oligomerization. Subsequently, the kinetics of monomer loss, due to oligomerization, was monitored at the individual residue level. The oligomerization reaction was found to be rate-limited by association and not conformational change, with an average reaction order of 2.6, across residues. Not surprisingly, salt accelerated the oligomerization kinetics, in a non-specific manner, by electrostatic screening of the highly charged monomers at acidic pH. Together, these results allowed a demarcation of the specific and non-specific effects of salt on prion protein misfolding and oligomerization.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2017.05.006}, author = {Sengupta, Ishita and Bhate, Suhas H and Das, Ranabir and Udgaonkar, Jayant B} } @article {11591, title = {A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.}, journal = {Neurobiol Dis}, volume = {98}, year = {2017}, month = {11/2016}, pages = {77-87}, abstract = {

Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs.

}, issn = {1095-953X}, doi = {10.1016/j.nbd.2016.11.012}, author = {Hindle, Samantha J and Hebbar, Sarita and Schwudke, Dominik and Elliott, Christopher J H and Sweeney, Sean T} } @article {11589, title = {Sedative effect of Clozapine is a function of 5-HT2A and environmental novelty.}, journal = {Eur Neuropsychopharmacol}, volume = {27}, year = {2017}, month = {12/2016}, pages = {70-81}, abstract = {

Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT2A knockout (Htr2a(-/-)) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic- Clozapine. We observed that Htr2a(-/-) mice were more resistant to Clozapine-induced suppression of activity (CISA) and this behaviour was dependent on the environment being {\textquoteright}novel{\textquoteright}. In their {\textquoteright}home{\textquoteright} environment, at identical doses the mice exhibited CISA. Interestingly, the effect of genotype and environmental novelty on CISA could not be extended to the other antipsychotics that were tested, i.e. Haloperidol and Risperidone. Haloperidol-induced activity suppression was independent of context and genotype. Whereas context affected Risperidone-induced activity suppression only in the Htr2a(+/+) mice. Furthermore, we observed that caffeine, a stimulant, elicited resistance to CISA similar to that seen in the {\textquoteright}novel{\textquoteright} context. Our study establishes a previously unknown interaction between the environmental context, 5-HT2A and CISA and emphasises the role of non-pharmacological factors such as environment on the effects of the drug, which seem antipsychotic-specific. Our findings should advance the understanding of the side effects of individual antipsychotics and the role of environment to overcome side effects such as sedation.

}, issn = {1873-7862}, doi = {10.1016/j.euroneuro.2016.10.007}, author = {Joshi, Radhika S and Quadros, Rolen and Drumm, Michael and Ain, Rupasri and Panicker, Mitradas M} } @article {14060, title = {Serological Evidence of Lyssavirus Infection among Bats in Nagaland, a North-Eastern State in India.}, journal = {Epidemiol Infect}, year = {2017}, month = {2017 Feb 23}, pages = {1-7}, abstract = {

Bats are known to be reservoirs of several medically important viruses including lyssaviruses. However, no systematic surveillance for bat rabies has been carried out in India, a canine rabies endemic country with a high burden of human rabies. Surveillance for rabies virus (RABV) infection in bats was therefore carried out in Nagaland, a north-eastern state in India at sites with intense human-bat interfaces during traditional bat harvests. Brain tissues and sera from bats were tested for evidence of infection due to RABV. Brain tissues were subjected to the fluorescent antibody test for detection of viral antigen and real-time reverse transcriptase PCR for presence of viral RNA. Bat sera were tested for the presence of rabies neutralizing antibodies by the rapid fluorescent focus inhibition test. None of the bat brains tested (n = 164) were positive for viral antigen or viral RNA. However, rabies neutralizing antibodies were detected in 4/78 (5{\textperiodcentered}1\%) bat sera tested, suggesting prior exposure to RABV or related lyssaviruses. The serological evidence of lyssaviral infection in Indian bats may have important implications in disease transmission and rabies control measures, and warrant extensive bat surveillance to better define the prevalence of lyssaviral infection in bats.

}, issn = {1469-4409}, doi = {10.1017/S0950268817000310}, author = {Mani, R S and Dovih, D P and Ashwini, M A and Chattopadhyay, B and Harsha, P K and Garg, K M and Sudarshan, S and Puttaswamaiah, R and Ramakrishnan, U and Madhusudana, S N} } @article {12203, title = {Signatures of Mechanosensitive Gating.}, journal = {Biophys J}, volume = {112}, year = {2017}, month = {2017 Jan 10}, pages = {3-9}, abstract = {

The question of how mechanically gated membrane channels open and close is notoriously difficult to address, especially if the protein structure is not available. This perspective highlights the relevance of micropipette-aspirated single-particle tracking-used to obtain a channel{\textquoteright}s diffusion coefficient, D, as a function of applied membrane tension, σ-as an indirect assay for determining functional behavior in mechanosensitive channels. While ensuring that the protein remains integral to the membrane, such methods can be used to identify not only the gating mechanism of a protein, but also associated physical moduli, such as torsional and dilational rigidity, which correspond to the protein{\textquoteright}s effective shape change. As an example, three distinct D-versus-σ "signatures" are calculated, corresponding to gating by dilation, gating by tilt, and gating by a combination of both dilation and tilt. Both advantages and disadvantages of the approach are discussed.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2016.12.009}, author = {Morris, Richard G} } @article {11595, title = {Spatial vegetation patterns and neighborhood competition among woody plants in an East African savanna.}, journal = {Ecology}, year = {2017}, month = {02/2017}, abstract = {

The majority of research on savanna vegetation dynamics has focused on the coexistence of woody and herbaceous vegetation. Interactions among woody plants in savannas are relatively poorly understood. We present data from a 10-year longitudinal study of spatially explicit growth patterns of woody vegetation in an East African savanna following exclusion of large herbivores and in the absence of fire. We examined plant spatial patterns and quantified the degree of competition among woody individuals. Woody plants in this semi-arid savanna exhibit strongly clumped spatial distributions at scales of 1 - 5 m. However, analysis of woody plant growth rates relative to their conspecific and heterospecific neighbors revealed evidence for strong competitive interactions at neighborhood scales of up to 5 m for most woody plant species. Thus, woody plants were aggregated in clumps despite significantly decreased growth rates in close proximity to neighbors, indicating that the spatial distribution of woody plants in this region depends on dispersal and establishment processes rather than on competitive, density-dependent mortality. However, our documentation of suppressive effects of woody plants on neighbors also suggests a potentially important role for tree-tree competition in controlling vegetation structure and indicates that the balanced-competition hypothesis may contribute to well-known patterns in maximum tree cover across rainfall gradients in Africa. This article is protected by copyright. All rights reserved.

}, issn = {0012-9658}, doi = {10.1002/ecy.1659}, author = {Dohn, Justin and Augustine, David J and Hanan, Niall P and Ratnam, Jayashree and Sankaran, Mahesh} } @article {13269, title = {Spatio-temporal interactions facilitate large carnivore sympatry across a resource gradient.}, journal = {Proc Biol Sci}, volume = {284}, year = {2017}, month = {2017 Feb 08}, abstract = {

Species within a guild vary their use of time, space and resources, thereby enabling sympatry. As intra-guild competition intensifies, such behavioural adaptations may become prominent. We assessed mechanisms of facilitating sympatry among dhole (Cuon alpinus), leopard (Panthera pardus) and tiger (Panthera tigris) in tropical forests of India using camera-trap surveys. We examined population-level temporal, spatial and spatio-temporal segregation among them across four reserves representing a gradient of carnivore and prey densities. Temporal and spatial overlaps were higher at lower prey densities. Combined spatio-temporal overlap was minimal, possibly due to chance. We found fine-scale avoidance behaviours at one high-density reserve. Our results suggest that: (i) patterns of spatial, temporal and spatio-temporal segregation in sympatric carnivores do not necessarily mirror each other; (ii) carnivores are likely to adopt temporal, spatial, and spatio-temporal segregation as alternative mechanisms to facilitate sympatry; and (iii) carnivores show adaptability across a gradient of resource availability, a driver of inter-species competition. We discuss behavioural mechanisms that permit carnivores to co-occupy rather than dominate functional niches, and adaptations to varying intensities of competition that are likely to shape structure and dynamics of carnivore guilds.

}, issn = {1471-2954}, doi = {10.1098/rspb.2016.1860}, author = {Karanth, K Ullas and Srivathsa, Arjun and Vasudev, Divya and Puri, Mahi and Parameshwaran, Ravishankar and Kumar, N Samba} } @article {12269, title = {Specificity and stability of transient protein-protein interactions.}, journal = {Curr Opin Struct Biol}, volume = {44}, year = {2017}, month = {2017 Jan 11}, pages = {77-86}, abstract = {

Remarkable features that are achieved in a protein-protein complex to precise levels are stability and specificity. Deviation from the normal levels of specificity and stability, which is often caused by mutations, could result in disease conditions. Chemical nature, 3-D arrangement and dynamics of interface residues code for both specificity and stability. This article reviews roles of interfacial residues in transient protein-protein complexes. It is proposed that aside from hotspot residues conferring stability to the complex, a small set of {\textquoteright}rigid{\textquoteright} residues at the interface that maintain conformation between complexed and uncomplexed forms, play a major role in conferring specificity. Exceptionally, {\textquoteright}super hotspot{\textquoteright} residues, which confer both stability and specificity, are attractive sites for interaction with small molecule inhibitors.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2016.12.010}, author = {Vishwanath, Sneha and Sukhwal, Anshul and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {17148, title = {Spontaneous Ca(2+) Influx in Drosophila Pupal Neurons Is Modulated by IP3-Receptor Function and Influences Maturation of the Flight Circuit.}, journal = {Front Mol Neurosci}, volume = {10}, year = {2017}, month = {2017}, pages = {111}, abstract = {

Inositol 1,4,5-trisphosphate receptors (IP3R) are Ca(2+) channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP3, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP3-mediated Ca(2+) release, and the resulting depletion of the ER store, triggers entry of extracellular Ca(2+) by store-operated Ca(2+) entry (SOCE). Mutations in IP3R attenuate SOCE. Compromised IP3R function and SOCE during pupal development of Drosophila leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development. To understand the effect of compromised IP3R function on pupal neuronal calcium signaling, we examined the effects of mutations in the IP3R gene (itpr) on Ca(2+) signals in cultured neurons derived from Drosophila pupae. We observed increased spontaneous Ca(2+) influx across the PM of isolated pupal neurons with mutant IP3R and also a loss of SOCE. Both spontaneous Ca(2+) influx and reduced SOCE were reversed by over-expression of dOrai and dSTIM, which encode the SOCE Ca(2+) channel and the ER Ca(2+)-sensor that regulates it, respectively. Expression of voltage-gated Ca(2+) channels (cac, Ca-α1D and Ca-αT) was significantly reduced in itpr mutant neurons. However, expression of trp mRNAs and transient receptor potential (TRP) protein were increased, suggesting that TRP channels might contribute to the increased spontaneous Ca(2+) influx in neurons with mutant IP3R. Thus, IP3R/SOCE modulates spontaneous Ca(2+) influx and expression of PM Ca(2+) channels in Drosophila pupal neurons. Spontaneous Ca(2+) influx compensates for the loss of SOCE in Drosophilaitpr mutant neurons.

}, doi = {10.3389/fnmol.2017.00111}, author = {Chakraborty, Sumita and Hasan, Gaiti} } @article {17516, title = {A statistical approach to understanding reproductive isolation in two sympatric species of tree crickets.}, journal = {J Exp Biol}, volume = {220}, year = {2017}, month = {2017 Apr 01}, pages = {1222-1232}, abstract = {

In acoustically communicating animals, reproductive isolation between sympatric species is usually maintained through species-specific calls. This requires that the receiver be tuned to the conspecific signal. Mapping the response space of the receiver onto the signal space of the conspecific investigates this tuning. A combinatorial approach to investigating the response space is more informative as the influence on the receiver of the interactions between the features is also elucidated. However, most studies have examined individual preference functions rather than the multivariate response space. We studied the maintenance of reproductive isolation between two sympatric tree cricket species (Oecanthus henryi and Oecanthus indicus) through the temporal features of the calls. Individual response functions were determined experimentally for O. henryi, the results from which were combined in a statistical framework to generate a multivariate quantitative receiver response space. The predicted response was higher for the signals of the conspecific than for signals of the sympatric heterospecific, indicating maintenance of reproductive isolation through songs. The model allows prediction of response to untested combinations of temporal features as well as delineation of the evolutionary constraints on the signal space. The model can also be used to predict the response of O. henryi to other heterospecific signals, making it a useful tool for the study of the evolution and maintenance of reproductive isolation via long-range acoustic signals.

}, issn = {1477-9145}, doi = {10.1242/jeb.146852}, author = {Bhattacharya, Monisha and Isvaran, Kavita and Balakrishnan, Rohini} } @article {20350, title = {Stepwise Assembly of β-Sheet Structure during the Folding of an SH3 Domain Revealed by a Pulsed Hydrogen Exchange Mass Spectrometry Study.}, journal = {Biochemistry}, year = {2017}, month = {2017 Jul 14}, abstract = {

Dissecting temporally the sequence of secondary structural changes, and determining how these specific changes modulate conformational heterogeneity, remain major goals of protein folding studies. In this study, the folding of the SH3 domain of PI3 kinase has been characterized using pulsed hydrogen exchange mass spectrometry (HX-MS). The folding could be described as a four-state process, U <-> IVE <-> IE <-> N, where IVE and IE are structurally heterogeneous intermediate ensembles. Compared to U, early intermediate IVE has a marginally increased level of protection against HX of amides along the entire length of the polypeptide. Sequential assembly into β-sheet structure has been resolved temporally. Three of the five β-strands acquire nativelike structure before the rate-limiting step. β-Strands 2 and 5 acquire nativelike structure in IVE, while β-strand 4 does so in IE. β-Strand 1 acquires nativelike structure only during the last step of the folding process. Hence, the HX-MS study has resolved the order of assembly of the β-strands for the formation of the two β-sheets, which previous studies utilizing Φ-value analysis of several different SH3 domains had been unable to accomplish. Moreover, it is shown that structural heterogeneity decreases in a stepwise manner during the three stages of folding.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.7b00374}, author = {Aghera, Nilesh and Udgaonkar, Jayant B} } @article {24895, title = {Structural and functional analysis of SMO-1, the SUMO homolog in Caenorhabditis elegans.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0186622}, abstract = {

SUMO proteins are important post-translational modifiers involved in multiple cellular pathways in eukaryotes, especially during the different developmental stages in multicellular organisms. The nematode C. elegans is a well known model system for studying metazoan development and has a single SUMO homolog, SMO-1. Interestingly, SMO-1 modification is linked to embryogenesis and development in the nematode. However, high-resolution information about SMO-1 and the mechanism of its conjugation is lacking. In this work, we report the high-resolution three dimensional structure of SMO-1 solved by NMR spectroscopy. SMO-1 has flexible N-terminal and C-terminal tails on either side of a rigid beta-grasp folded core. While the sequence of SMO-1 is more similar to SUMO1, the electrostatic surface features of SMO-1 resemble more with SUMO2/3. SMO-1 can bind to typical SUMO Interacting Motifs (SIMs). SMO-1 can also conjugate to a typical SUMOylation consensus site as well as to its natural substrate HMR-1. Poly-SMO-1 chains were observed in-vitro even though SMO-1 lacks any consensus SUMOylation site. Typical deSUMOylation enzymes like Senp2 can cleave the poly-SMO-1 chains. Despite being a single gene, the SMO-1 structure allows it to function in a large repertoire of signaling pathways involving SUMO in C. elegans. Structural and functional features of SMO-1 studies described here will be useful to understand its role in development.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0186622}, author = {Surana, Parag and Gowda, Chandrakala M and Tripathi, Vasvi and Broday, Limor and Das, Ranabir} } @article {24299, title = {A structural map of oncomiR-1 at single-nucleotide resolution.}, journal = {Nucleic Acids Res}, volume = {45}, year = {2017}, month = {2017 Sep 19}, pages = {9694-9705}, abstract = {

The miR-17-92a cluster, also known as {\textquoteright}oncomiR-1{\textquoteright}, is an RNA transcript that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. Its dysregulation underlies the development of several cancers. Oncomir-1 comprises six constituent miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. The structural mechanisms that regulate such differential processing are unknown, and this has impeded our understanding of the dysregulation of oncomiR-1 in pathophysiology. By probing the sensitivity of each nucleotide in oncomiR-1 to reactive small molecules, we present a secondary structural map of this RNA at single-nucleotide resolution. The secondary structure and solvent accessible regions of oncomiR-1 reveal that most of its primary microRNA domains are suboptimal substrates for Drosha-DGCR8, and therefore resistant to microprocessing. The structure indicates that the binding of trans-acting factors is required to remodel the tertiary organization and unmask cryptic primary microRNA domains to facilitate their processing into pre-microRNAs.

}, issn = {1362-4962}, doi = {10.1093/nar/gkx613}, author = {Chakraborty, Saikat and Krishnan, Yamuna} } @article {26578, title = {Successional status, seed dispersal mode and overstorey species influence tree regeneration in tropical rain-forest fragments in Western Ghats, India}, journal = {Journal of Tropical Ecology}, volume = {33}, year = {2017}, month = {07/2017}, pages = {270-284}, abstract = {

The effects of fragmentation and overstorey tree diversity on tree regeneration were assessed in tropical rain forests of the Western Ghats, India. Ninety plots were sampled for saplings (1{\textendash}5 cm diameter at breast height (dbh); 5{\texttimes}5-m plots) and overstorey trees (\>9.55 cm dbh; 20{\texttimes}20-m plots) within two fragments (32 ha and 18 ha) and two continuous forests. We tested the hypotheses that fragmentation and expected seed-dispersal declines (1) reduce sapling densities and species richness of all species and old-growth species, and increase recruitment of early-successional species, (2) reduce the prevalence of dispersed recruits and (3) increase influence of local overstorey on sapling densities and richness. Continuous forests and fragments had similar sapling densities and species richness overall, but density and richness of old-growth species declined by 62\% and 48\%, respectively, in fragments. Fragments had 39\% lower densities and 24\% lower richness of immigrant saplings (presumed dispersed into sites as conspecific adults were absent nearby), and immigrant densities of old-growth bird-dispersed species declined by 79\%. Sapling species richness (overall and old-growth) increased with overstorey species richness in fragments, but was unrelated to overstorey richness in continuous forests. Our results show that while forest fragments retain significant sapling diversity, losses of immigrant recruits and increased overstorey influence strengthen barriers to natural regeneration of old-growth tropical rain forests.

}, doi = {10.1017/S0266467417000219}, author = {Osuri, Anand M and chakravarthy, Dayani and Divya Mudappa and Raman, Shankar TR and Ayyappan, N and Muthuramkumar, S and Parthasarathy, N} } @article {28253, title = {Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes in~vivo.}, journal = {Microbes Infect}, volume = {19}, year = {2017}, month = {2017 Nov}, pages = {515-526}, abstract = {

Mycobacterium tuberculosis is one of the most successful pathogens known, having infected more than a third of the global population. An important strategy for intracellular survival of pathogenic mycobacteria relies on their capacity to resist delivery to lysosomes, instead surviving within macrophage phagosomes. Several factors of both mycobacterial and host origin have been implicated in this process. However, whether or not this strategy is employed in\ vivo is not clear. Here we show that in\ vivo, following intravenous infection, M. tuberculosis and Mycobacterium bovis BCG initially survived by resisting lysosomal transfer. However, after prolonged infection the bacteria were transferred to lysosomes yet continued to proliferate. A M. bovis BCG mutant lacking protein kinase G (PknG), that cannot avoid lysosomal transfer and is readily cleared in\ vitro, was found to survive and proliferate in\ vivo. The ability to survive and proliferate in lysosomal organelles in\ vivo was found to be due to an altered host environment rather than changes in the inherent ability of the bacteria to arrest phagosome maturation. Thus, within an infected host, both M. tuberculosis and M. bovis BCG adapts to infection-specific host responses. These results are important to understand the pathology of tuberculosis and may have implications for the development of effective strategies to combat tuberculosis.

}, issn = {1769-714X}, doi = {10.1016/j.micinf.2017.06.008}, author = {Sundaramurthy, Varadharajan and Korf, Hannelie and Singla, Ashima and Scherr, Nicole and Nguyen, Liem and Ferrari, Giorgio and Landmann, Regine and Huygen, Kris and Pieters, Jean} } @article {16562, title = {Synaptic input sequence discrimination on behavioral time-scales mediated by reaction-diffusion chemistry in dendrites.}, journal = {Elife}, volume = {6}, year = {2017}, month = {2017 Apr 19}, abstract = {

Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here we show that synaptically-driven reaction-diffusion pathways on dendrites can perform sequence discrimination on behaviorally relevant time-scales. We used abstract signaling models to show that selectivity arises when inputs at successive locations are aligned with, and amplified by, propagating chemical waves triggered by previous inputs. We incorporated biological detail using sequential synaptic input onto spines in morphologically, electrically, and chemically detailed pyramidal neuronal models based on rat data. Again, sequences were recognized, and local channel modulation downstream of putative sequence-triggered signaling could elicit changes in neuronal firing. We predict that dendritic sequence-recognition zones occupy 5 to 30 microns and recognize time-intervals of 0.2 to 5s. We suggest that this mechanism provides highly parallel and selective neural computation in a functionally important time range.

}, issn = {2050-084X}, doi = {10.7554/eLife.25827}, author = {Bhalla, Upinder Singh} } @article {24298, title = {Taxonomic overview of the hyperdiverse ant genus Tetramorium Mayr (Hymenoptera, Formicidae) in India with descriptions and X-ray microtomography of two new species from the Andaman Islands.}, journal = {PeerJ}, volume = {5}, year = {2017}, month = {2017}, pages = {e3800}, abstract = {

With 600 described species, the ant genus Tetramorium represents one of the most species-rich ant radiations. However, much work remains to fully document the hyperdiversity of this remarkable group. Tetramorium, while globally distributed, is thought to have originated in the Afrotropics and is particularly diverse in the Old World. Here, we focus attention on the Tetramorium fauna of India, a region of high biodiversity value and interest for conservation. We overview Tetramorium diversity in India by providing a species list, accounts of all species groups present, an illustrated identification key to Indian Tetramorium species groups and notes on the Indian Tetramorium fauna. Further, we describe two new species, Tetramorium krishnani sp. n. and Tetramorium jarawa sp. n. from the Andaman Islands archipelago and embed them into currently recognized Tetramorium tonganum and Tetramorium inglebyi species groups. We also provide illustrated species level keys for these groups. Along with detailed species descriptions and high-resolution montage images of types, we provide 3D cybertypes of the new species derived from X-ray micro-computed tomography.

}, issn = {2167-8359}, doi = {10.7717/peerj.3800}, author = {Agavekar, Gaurav and Hita Garcia, Francisco and Economo, Evan P} } @article {26574, title = {On the taxonomic status of Eurylepis poonaensis (Squamata: Scincidae): resolving a long-standing conundrum}, journal = {SALAMANDRA}, volume = {53}, year = {2017}, month = {08/2017}, pages = {389-397}, abstract = {

The scincid genus Eurylepis was split off from the cosmopolitan genus Eumeces sensu lato, with Eurylepis taeniolatus
being the type species, which is taxonomically poorly understood. The other nominate species in this genus is
Eurylepis poonaensis, which was known only from its type locality and original description, and is the only known member
of the subfamily Scincinae from near the Western Ghats. However, earlier studies raised doubts about its specific validity,
often without examining type or other specimens. We collected fresh samples of this species from the type locality
and nearby areas. Based on the examination of the holotype and the new material, we provide a detailed redescription of
E. poonaensis, additional data on its skeletal structure, habitat, and natural history. We also provide a detailed redescription
of E. taeniolatus based on the holotype to avoid further taxonomic ambiguity.

}, author = {Datta-Roy, Aniruddha and Deepak, V. and Chaitanya, R and Murthy, Channakeshva and Harshal Bhosale and Lajmi, Aparna and Karanth, K. Praveen and Kunte, Krushnamegh and Giri, Varad} } @article {24894, title = {The threshold algorithm: Description of the methodology and new developments.}, journal = {J Chem Phys}, volume = {147}, year = {2017}, month = {2017 Oct 21}, pages = {152713}, abstract = {

Understanding the dynamics of complex systems requires the investigation of their energy landscape. In particular, the flow of probability on such landscapes is a central feature in visualizing the time evolution of complex systems. To obtain such flows, and the concomitant stable states of the systems and the generalized barriers among them, the threshold algorithm has been developed. Here, we describe the methodology of this approach starting from the fundamental concepts in complex energy landscapes and present recent new developments, the threshold-minimization algorithm and the molecular dynamics threshold algorithm. For applications of these new algorithms, we draw on landscape studies of three disaccharide molecules: lactose, maltose, and sucrose.

}, issn = {1089-7690}, doi = {10.1063/1.4985912}, author = {Neelamraju, Sridhar and Oligschleger, Christina and Sch{\"o}n, J Christian} } @article {26658, title = {Time Correlations in Mode Hopping of Coupled Oscillators}, journal = {Journal of Statistical Physics}, volume = {167}, year = {2017}, month = {05/2017}, pages = {792{\textendash}805}, abstract = {

We study the dynamics in a system of coupled oscillators when Arnold Tongues overlap. By varying the initial conditions, the deterministic system can be attracted to different limit cycles. Adding noise, the mode hopping between different states become a dominating part of the dynamics. We simplify the system through a Poincare section, and derive a 1D model to describe the dynamics. We explain that for some parameter values of the external oscillator, the time distribution of occupancy in a state is exponential and thus memoryless. In the general case, on the other hand, it is a sum of exponential distributions characteristic of a system with time correlations.

}, author = {Heltberg, ML and Krishna, Sandeep and Jensen, Mogens H} } @article {26655, title = {Tracking the variability of phenotypic traits on a molecular phylogeny: an example from scolopendrid centipedes in peninsular India}, journal = {Organisms Diversity \& Evolution}, volume = {17}, year = {2017}, month = {07/2017}, pages = {393{\textendash}408}, abstract = {

Taxonomic studies on scolopendrid centipedes have often documented variability at the individual and population levels and applied those data to questions of species delimitation, but these investigations have mostly lacked an explicit phylogenetic framework. A molecular phylogeny and recent taxonomic revision for Indian species of the scolopendrid Digitipes Attems, 1930, permit variability of traditional taxonomic characters for Scolopendridae to be mapped onto a phylogeny. Based on their fit to the tree using maximum likelihood, reliable species-level characters include the number of glabrous antennal articles, presence of a median ridge on the tergites, and presence or absence of a tarsal spur on leg 20. Characters that are conserved within and diagnostic for particular species but labile within others (typically with geographic structure) include the first tergite with paramedian sutures, presence or absence of a lateral spine on the coxopleuron, and the number of spines in a ventromedial row on the ultimate leg prefemur. Comparisons with published accounts of variability in species of other scolopendrid genera, particularly Scolopendra and Otostigmus, show that Indian Digitipes has conserved morphology in some characters that are taxonomically useful elsewhere in the family, and most of its taxonomically informative characters have analogous patterns of variability in other genera. The approach used in this study to evaluate morphological variation in a phylogenetic framework can be applied to other taxa in which morphologically cryptic species have been reported and where species diagnosis requires a combination of characters.

}, author = {Joshi, Jahnavi and Edgecombe, GD} } @article {19198, title = {Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio.}, journal = {G3 (Bethesda)}, year = {2017}, month = {2017 Jun 16}, abstract = {

Several genes that have been implicated in autism spectrum disorders are large and have multiple transcripts. Neurons are especially enriched with longer transcripts compared to non-neural cell types. The human autism susceptibility candidate 2 (AUTS2) gene is ~1.2 Mb long and is implicated in a number of neurological disorders including autism, intellectual disability, addiction and developmental delay. Recent studies show AUTS2 to be important for activation of transcription of neural specific genes, neuronal migration and neurite outgrowth. However, much remains to be understood regarding the transcriptional complexity and the functional roles of AUTS2 in neurodevelopment. Zebrafish provide an excellent model system for studying both these questions. We undertook genomic identification and characterization of auts2 and its paralogous genes in zebrafish. There are four auts2 family genes in zebrafish: auts2a, auts2b, fbrsl1 and fbrs The absence of complete annotation of their structures hampers functional studies. We present evidence for transcriptional complexity of these four genes mediated by alternative splicing and alternative promoter usage. Furthermore, the expression of the various paralogs is tightly regulated both spatially and developmentally. Our findings suggest that auts2 paralogs serve distinct functions in the development and functioning of target tissues.

}, issn = {2160-1836}, doi = {10.1534/g3.117.042622}, author = {Kondrychyn, Igor and Robra, Lena and Thirumalai, Vatsala} } @article {12891, title = {Two new genera of songbirds represent endemic radiations from the Shola Sky Islands of the Western Ghats, India.}, journal = {BMC Evol Biol}, volume = {17}, year = {2017}, month = {2017 Jan 23}, pages = {31}, abstract = {

BACKGROUND: A long-standing view of Indian biodiversity is that while rich in species, there are few endemics or in-situ radiations within the subcontinent. One exception is the Western Ghats biodiversity hotspot, an isolated mountain range with many endemic species. Understanding the origins of the montane-restricted species is crucial to illuminate both taxonomic and environmental history.

RESULTS: With evidence from genetic, morphometric, song, and plumage data, we show that two songbird lineages endemic to the Western Ghats montane forest each have diversified into multiple distinct species. Historically labeled as single species of widespread Asian genera, these two lineages are highly divergent and do not group with the taxa in which they were previously classified but rather are distinct early divergences in larger Asian clades of flycatchers and babblers. Here we designated two new genera, the Western Ghats shortwings as Sholicola and the laughingthrushes as Montecincla, and evaluated species-limits to reflect distinct units by revising six previously named taxa and describing one novel species. Divergence dating showed that both these montane groups split from their Himalayan relatives during the Miocene, which is coincident with a shift towards arid conditions that fragmented the previously contiguous humid forest across peninsular India and isolated these lineages in the Western Ghats. Furthermore, these two genera showed congruent patterns of diversification across the Western Ghats Sky Islands, coincident with other climatic changes.

CONCLUSION: Our study reveals the existence of two independent endemic radiations in the high montane Western Ghats or Shola Sky Islands with coincident divergence times, highlighting the role of climate in the diversification of these ancient lineages. The endemic and highly divergent nature of these previously unrecognized species underscores the dearth of knowledge about the biogeography of the Asian tropics, even for comparatively well-known groups such as birds. The substantial increase in the diversity of this region underscores the need for more rigorous systematic analysis to inform biodiversity studies and conservation efforts.

}, issn = {1471-2148}, doi = {10.1186/s12862-017-0882-6}, author = {Robin, V V and Vishnudas, C K and Gupta, Pooja and Rheindt, Frank E and Hooper, Daniel M and Ramakrishnan, Uma and Reddy, Sushma} } @article {25695, title = {Two new species of Langelurillus Pr{\'o}chniewicz, 1994 from India (Araneae: Salticidae: Aelurillina)}, journal = {Zootaxa}, volume = {4318}, year = {2017}, month = {09/2017}, pages = {135-146}, abstract = {

Two new species, Langelurillus lacteus sp. nov. and L. onyx sp. nov., are described from India. Detailed illustrations and record map are given.

}, doi = {10.11646/zootaxa.4318.1.6}, author = {Sanap, Rajesh V and Joglekar, A and Prajapati, D and Caleb, JTD} } @article {28250, title = {Two new substituted polychiral 5, 6-dihydro-alpha-pyrones from Orthosiphon diffusus and molecular docking studies}, journal = {PHYTOCHEMISTRY LETTERS}, volume = {22}, year = {2017}, month = {12/2017}, pages = { 21-26}, abstract = {

Chemical investigation on Orthosiphon diffusus lead to isolation of two new substituted polychiral 5, 6-dihydro-alpha-pyrones, orthodiffenes E-F (5-6) which were characterized from the detailed studies of their 1D and 2D NMR spectra. Isolated molecules orthodiffenes E-F (5-6) along with previously isolated, reported orthodiffene A-D (14) molecules were subjected to in silico studies and analysed for anticancer target Topoisomerse I-B - DNA complex. Orthodiffene D and E are giving noteworthy observations while all isolated molecules are showing a pattern of binding in active pocket similar to each other however, different from Camptothecin, an anticancer agent. Orthodiffene A-C have comparable cytotoxicity to Camptothecin, which we have earlier reported.

}, doi = {10.1016/j.phytol.2017.08.006}, author = {Holla, Harish and Sharma, Akanksha and Bhat, Pritesh and Shinde, Dhananjay and Das, Biswanath} } @article {26282, title = {UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes.}, journal = {PLoS Genet}, volume = {13}, year = {2017}, month = {2017 Nov 16}, pages = {e1007100}, abstract = {

JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex. AP1 regulates the size but not the composition of SVP transport carriers. Additionally, UNC-16 and LRK-1 through the AP-3 complex regulates the composition but not the size of the SVP transport carrier. These early biogenesis steps are essential for dependence on the synaptic vesicle motor, UNC-104 for axonal transport. Our results show that UNC-16 and its downstream effectors, LRK-1 and the AP complexes function at the Golgi and/or post-Golgi compartments to control early steps of SV biogenesis. The UNC-16 dependent steps of exclusion, inclusion and motor recruitment are critical for polarized distribution of neuronal cargo.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1007100}, author = {Choudhary, Bikash and Kamak, Madhushree and Ratnakaran, Neena and Kumar, Jitendra and Awasthi, Anjali and Li, Chun and Nguyen, Ken and Matsumoto, Kunihiro and Hisamoto, Naoki and Koushika, Sandhya P} } @article {25264, title = {Understanding protein domain-swapping using structure-based models of protein folding.}, journal = {Prog Biophys Mol Biol}, volume = {128}, year = {2017}, month = {2017 Sep}, pages = {113-120}, abstract = {

In domain-swapping, two or more identical protein monomers exchange structural elements and fold into dimers or multimers whose units are structurally similar to the original monomer. Domain-swapping is of biotechnological interest because inhibiting domain-swapping can reduce disease-causing fibrillar protein aggregation. To achieve such inhibition, it is important to understand both the energetics that stabilize the domain-swapped structure and the protein dynamics that enable the swapping. Structure-based models (SBMs) encode the folded structure of the protein in their potential energy functions. SBMs have been successfully used to understand diverse aspects of monomer folding. Symmetrized SBMs model interactions between two identical protein chains using only intra-monomer interactions. Molecular dynamics simulations of such symmetrized SBMs have been used to correctly predict the domain-swapped structure and to understand the mechanism of domain-swapping. Here, we review such models and illustrate that monomer topology determines key aspects of domain-swapping. However, in some proteins, specifics of local energetic interactions modulate domain-swapping and these need to be added to the symmetrized SBMs. We then summarize some general principles of the mechanism of domain-swapping that emerge from the symmetrized SBM simulations. Finally, using our own results, we explore how symmetrized SBMs could be used to design domain-swapping in proteins.

}, keywords = {Models, Molecular, Protein Domains, Protein Folding, Proteins}, issn = {1873-1732}, doi = {10.1016/j.pbiomolbio.2016.09.013}, author = {Mascarenhas, Nahren Manuel and Gosavi, Shachi} } @article {20317, title = {Universal lower bound on the free-energy cost of molecular measurements.}, journal = {Phys Rev E}, volume = {95}, year = {2017}, month = {2017 Jun}, pages = {062410}, abstract = {

The living cell uses a variety of molecular receptors to read and process chemical signals that vary in space and time. We model the dynamics of such molecular level measurements as Markov processes in steady state, with a coupling between the receptor and the signal. We prove exactly that, when the signal dynamics is not perturbed by the receptors, the free energy consumed by the measurement process is lower bounded by a quantity proportional to the mutual information. Our result is completely independent of the receptor architecture and dependent on signal properties alone, and therefore holds as a general principle for molecular information processing.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.95.062410}, author = {Das, Suman G and Rao, Madan and Iyengar, Garud} } @article {17521, title = {Unsupervised Spike Sorting for Large-Scale, High-Density Multielectrode Arrays.}, journal = {Cell Rep}, volume = {18}, year = {2017}, month = {2017 Mar 07}, pages = {2521-2532}, abstract = {

We present a method for automated spike sorting for recordings with high-density, large-scale multielectrode arrays. Exploiting the dense sampling of single neurons by multiple electrodes, an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features is exploited for fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. Performance is demonstrated using recordings with a 4,096-channel array and validated using anatomical imaging, optogenetic\ stimulation, and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our approach demonstrates that it is feasible to reliably isolate the activity of up to thousands of neurons and that dense, multi-channel probes substantially aid reliable spike sorting.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2017.02.038}, author = {Hilgen, Gerrit and Sorbaro, Martino and Pirmoradian, Sahar and Muthmann, Jens-Oliver and Kepiro, Ibolya Edit and Ullo, Simona and Ramirez, Cesar Juarez and Puente Encinas, Albert and Maccione, Alessandro and Berdondini, Luca and Murino, Vittorio and Sona, Diego and Cella Zanacchi, Francesca and Sernagor, Evelyne and Hennig, Matthias Helge} } @article {25699, title = {Variance in Female Reproductive Success Differentially Impacts Effective Population Size in the Short-Nosed Fruit Bat, Cynopterus sphinx}, journal = {Evolutionary Biology}, volume = {44}, year = {2017}, month = {09/2017}, pages = {3066-373}, abstract = {

Effective population size (Ne) quantifies the effects of micro-evolutionary processes and the rate of loss of genetic diversity in a population. Several demographic and mating parameters reduce Ne. Theoretical studies elucidate the impacts of various demographic and mating system parameters on Ne, while empirical studies illustrate realized Ne for species with differing life histories and mating systems. However, effect of intra-specific variation in mating system on effective size remains largely unexplored. In this paper we investigated the effect of promiscuous and polygynous mating on Ne in two wild populations of the short-nosed fruit bat, Cynopterus sphinx. Ne/N (ratio of effective population size to census size) was lower than unity in both populations, and much lower for the polygynous population compared to promiscuous population. Elasticity analyses reveal that Ne/N was sensitive to deviations in the sex ratio. Variance in female reproductive success had a higher impact on Ne compared to variance in male reproductive success in the promiscuous population. However, for the polygynous population, impact of variance in male reproductive success on Ne was higher than that of variance in female reproductive success. Our results suggest that depending on mating system, different populations of the same species could have alternate evolutionary trajectories. The rate of loss of genetic diversity would be lower for the promiscuous population compared to the polygynous population. Our study is the first to highlight which parameters would most significantly impact population specific Ne under different mating systems.

}, doi = {10.1007/s11692-017-9414-y}, author = {Garg, Kritika M and Ramakrishnan, Uma} } @article {8348, title = {Active fluidization in dense glassy systems.}, journal = {Soft Matter}, volume = {12}, year = {2016}, month = {2016 Jul 20}, pages = {6268-76}, abstract = {

Dense soft glasses show strong collective caging behavior at sufficiently low temperatures. Using molecular dynamics simulations of a model glass former, we show that the incorporation of activity or self-propulsion, f0, can induce cage breaking and fluidization, resulting in the disappearance of the glassy phase beyond a critical f0. The diffusion coefficient crosses over from being strongly to weakly temperature dependent as f0 is increased. In addition, we demonstrate that activity induces a crossover from a fragile to a strong glass and a tendency of active particles to cluster. Our results are of direct relevance to the collective dynamics of dense active colloidal glasses and to recent experiments on tagged particle diffusion in living cells.

}, issn = {1744-6848}, doi = {10.1039/c5sm02950c}, author = {Mandal, Rituparno and Bhuyan, Pranab Jyoti and Rao, Madan and Dasgupta, Chandan} } @article {3546, title = {Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 Mar 22}, pages = {E1645-54}, abstract = {

The surface of a living cell provides a platform for receptor signaling, protein sorting, transport, and endocytosis, whose regulation requires the local control of membrane organization. Previous work has revealed a role for dynamic actomyosin in membrane protein and lipid organization, suggesting that the cell surface behaves as an active composite composed of a fluid bilayer and a thin film of active actomyosin. We reconstitute an analogous system in vitro that consists of a fluid lipid bilayer coupled via membrane-associated actin-binding proteins to dynamic actin filaments and myosin motors. Upon complete consumption of ATP, this system settles into distinct phases of actin organization, namely bundled filaments, linked apolar asters, and a lattice of polar asters. These depend on actin concentration, filament length, and actin/myosin ratio. During formation of the polar aster phase, advection of the self-organizing actomyosin network drives transient clustering of actin-associated membrane components. Regeneration of ATP supports a constitutively remodeling actomyosin state, which in turn drives active fluctuations of coupled membrane components, resembling those observed at the cell surface. In a multicomponent membrane bilayer, this remodeling actomyosin layer contributes to changes in the extent and dynamics of phase-segregating domains. These results show how local membrane composition can be driven by active processes arising from actomyosin, highlighting the fundamental basis of the active composite model of the cell surface, and indicate its relevance to the study of membrane organization.

}, issn = {1091-6490}, doi = {10.1073/pnas.1514030113}, author = {K{\"o}ster, Darius Vasco and Husain, Kabir and Iljazi, Elda and Bhat, Abrar and Bieling, Peter and Mullins, R Dyche and Rao, Madan and Mayor, Satyajit} } @article {1619, title = {Agatoxin-like peptides in the neuroendocrine system of the honey bee and other insects.}, journal = {J Proteomics}, volume = {132}, year = {2016}, month = {2016 Jan 30}, pages = {77-84}, abstract = {

UNLABELLED: We investigated the peptide inventory of the corpora cardiaca (CC) of the honey bee, Apis mellifera, by direct tissue profiling using MALDI-TOF MS combined with proteomic approaches focusing on cysteine-containing peptides. An agatoxin-like peptide (ALP) was identified as a component of the glandular part of the CC and was associated with the presence of the adipokinetic hormone in mass spectra. Although abundant in the CC, ALP does not belong to the toxins observed in the venom gland of A. mellifera. Homologs of ALP are highly conserved in major groups of arthropods and in line with this we detected ALP in the CC of non-venomous insects such as cockroaches and silverfish. In the American cockroach, Periplaneta americana, ALP was also identified in the CNS and stomatogastric nervous system. This is the first report that establishes the presence of ALPs in the neuroendocrine tissues of insects and further studies are necessary to reveal common functions of these peptides, e.g. as antimicrobial agents, ion channel modulators or classical neuropeptides.

BIOLOGICAL SIGNIFICANCE: Among the messenger molecules of the nervous system, neuropeptides represent the structurally most diverse class and basically participate in the regulation of all physiological processes. The set of neuropeptides, their functions and spatial distribution are particularly well-studied in insects. Until now, however, several potential neuropeptide receptors remained orphan, which indicates the existence of so far unknown ligands. In our study, we used proteomic methods such as cysteine modification, enzymatic digestion and peptide derivatization, combined with direct tissue profiling by MALDI-TOF mass spectrometry, for the discovery of novel putative messenger molecules in the neuroendocrine system. The described presence of agatoxin-like peptides in the nervous system of the honey bee and other insects was overseen so far and is thus a remarkable addition to the very well studied neuropeptidome of insects. It is not yet clear, if these toxin-like peptides act as antimicrobial agents, ion channel modulators or classical neuropeptides.

}, issn = {1876-7737}, doi = {10.1016/j.jprot.2015.11.021}, author = {Sturm, Sebastian and Ramesh, Divya and Brockmann, Axel and Neupert, Susanne and Predel, Reinhard} } @article {5307, title = {Airflow and optic flow mediate antennal positioning in flying honeybees.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016}, abstract = {

To maintain their speeds during navigation, insects rely on feedback from their visual and mechanosensory modalities. Although optic flow plays an essential role in speed determination, it is less reliable under conditions of low light or sparse landmarks. Under such conditions, insects rely on feedback from antennal mechanosensors but it is not clear how these inputs combine to elicit flight-related antennal behaviours. We here show that antennal movements of the honeybee, Apis mellifera, are governed by combined visual and antennal mechanosensory inputs. Frontal airflow, as experienced during forward flight, causes antennae to actively move forward as a sigmoidal function of absolute airspeed values. However, corresponding front-to-back optic flow causes antennae to move backward, as a linear function of relative optic flow, opposite the airspeed response. When combined, these inputs maintain antennal position in a state of dynamic equilibrium.

}, issn = {2050-084X}, doi = {10.7554/eLife.14449}, author = {Roy Khurana, Taruni and Sane, Sanjay P} } @article {5301, title = {The Antsy Social Network: Determinants of Nest Structure and Arrangement in Asian Weaver Ants.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0156681}, abstract = {

Asian weaver ants (Oecophylla smaragdina) are arboreal ants that are known to form mutualistic complexes with their host trees. They are eusocial ants that build elaborate nests in the canopy in tropical areas. A colony comprises of multiple nests, usually on multiple trees, and the boundaries of the colony may be difficult to identify. However, they provide the ideal model for studying group living in invertebrates since there are a definite number of nests for a given substrate, the tree. Here, we briefly examine the structure of the nests and the processes involved in the construction and maintenance of these nests. We have described the spatial arrangement of weaver ant nests on trees in two distinct tropical clusters, a few hundred kilometres apart in India. Measurements were made for 13 trees with a total of 71 nests in the two field sites. We have considered a host of biotic and abiotic factors that may be crucial in determining the location of the nesting site by Asian weaver ants. Our results indicate that tree characteristics and architecture followed by leaf features help determine nest location in Asian weaver ants. While environmental factors may not be as influential to nest arrangement, they seem to be important determinants of nest structure. The parameters that may be considered in establishing the nests could be crucial in picking the evolutionary drivers for colonial living in social organisms.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0156681}, author = {Devarajan, Kadambari} } @article {3545, title = {An Approach to Function Annotation for Proteins of Unknown Function (PUFs) in the Transcriptome of Indian Mulberry.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0151323}, abstract = {

The modern sequencing technologies are generating large volumes of information at the transcriptome and genome level. Translation of this information into a biological meaning is far behind the race due to which a significant portion of proteins discovered remain as proteins of unknown function (PUFs). Attempts to uncover the functional significance of PUFs are limited due to lack of easy and high throughput functional annotation tools. Here, we report an approach to assign putative functions to PUFs, identified in the transcriptome of mulberry, a perennial tree commonly cultivated as host of silkworm. We utilized the mulberry PUFs generated from leaf tissues exposed to drought stress at whole plant level. A sequence and structure based computational analysis predicted the probable function of the PUFs. For rapid and easy annotation of PUFs, we developed an automated pipeline by integrating diverse bioinformatics tools, designated as PUFs Annotation Server (PUFAS), which also provides a web service API (Application Programming Interface) for a large-scale analysis up to a genome. The expression analysis of three selected PUFs annotated by the pipeline revealed abiotic stress responsiveness of the genes, and hence their potential role in stress acclimation pathways. The automated pipeline developed here could be extended to assign functions to PUFs from any organism in general. PUFAS web server is available at http://caps.ncbs.res.in/pufas/ and the web service is accessible at http://capservices.ncbs.res.in/help/pufas.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0151323}, author = {Dhanyalakshmi, K H and Naika, Mahantesha B N and Sajeevan, R S and Mathew, Oommen K and Shafi, K Mohamed and Sowdhamini, Ramanathan and N Nataraja, Karaba} } @article {4552, title = {On the Archaeal Origins of Eukaryotes and the Challenges of Inferring Phenotype from Genotype}, journal = {Trends in Cell Biology}, volume = {26, }, year = {2016}, month = {July 2016}, pages = {476{\textendash}485}, abstract = {

If eukaryotes arose through a merger between archaea and bacteria, what did the first true eukaryotic cell look like? A major step toward an answer came with the discovery of Lokiarchaeum, an archaeon whose genome encodes small GTPases related to those used by eukaryotes to regulate membrane traffic. Although {\textquoteleft}Loki{\textquoteright} cells have yet to be seen, their existence has prompted the suggestion that the archaeal ancestor of eukaryotes engulfed the future mitochondrion by phagocytosis. We propose instead that the archaeal ancestor was a relatively simple cell, and that eukaryotic cellular organization arose as the result of a gradual transfer of bacterial genes and membranes driven by an ever-closer symbiotic partnership between a bacterium and an archaeon

}, doi = { http://dx.doi.org/10.1016/j.tcb.2016.03.009}, author = {Gautam Dey and Mukund Thattai and Buzz Baum} } @article {9604, title = {Blue protein with red fluorescence.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 Oct 11}, pages = {11513-11518}, abstract = {

The walleye (Sander vitreus) is a golden yellow fish that inhabits the Northern American lakes. The recent sightings of the blue walleye and the correlation of its sighting to possible increased UV radiation have been proposed earlier. The underlying molecular basis of its adaptation to increased UV radiation is the presence of a protein (Sandercyanin)-ligand complex in the mucus of walleyes. Degradation of heme by UV radiation results in the formation of Biliverdin IXα (BLA), the chromophore bound to Sandercyanin. We show that Sandercyanin is a monomeric protein that forms stable homotetramers on addition of BLA to the protein. A structure of the Sandercyanin-BLA complex, purified from the fish mucus, reveals a glycosylated protein with a lipocalin fold. This protein-ligand complex absorbs light in the UV region (λmax of 375 nm) and upon excitation at this wavelength emits in the red region (λmax of 675 nm). Unlike all other known biliverdin-bound fluorescent proteins, the chromophore is noncovalently bound to the protein. We provide here a molecular rationale for the observed spectral properties of Sandercyanin.

}, issn = {1091-6490}, doi = {10.1073/pnas.1525622113}, author = {Ghosh, Swagatha and Yu, Chi-Li and Ferraro, Daniel J and Sudha, Sai and Pal, Samir Kumar and Schaefer, Wayne F and Gibson, David T and Ramaswamy, S} } @article {1620, title = {Brain regions and molecular pathways responding to food reward type and value in honey bees.}, journal = {Genes Brain Behav}, volume = {15}, year = {2016}, pages = {305-17}, abstract = {

The ability of honey bees to evaluate differences in food type and value is crucial for colony success, but these assessments are made by individuals who bring food to the hive, eating little, if any, of it themselves. We tested the hypothesis that responses to food type (pollen or nectar) and value involve different subsets of brain regions, and genes generally, responsive to food. mRNA in situ hybridization of c-jun revealed that brain regions responsive to differences in food type were mostly different from regions responsive to differences in food value, except those dorsal and lateral to the mushroom body calyces, which responded to all three. Transcriptomic profiles of the mushroom bodies generated by RNA sequencing gave the following results: 1) responses to differences in food type or value included a subset of molecular pathways involved in the response to food reward; 2) genes responsive to food reward, food type and food value were enriched for (the Gene Ontology categories) mitochondrial and endoplasmic reticulum activity; 3) genes responsive to only food and food type were enriched for regulation of transcription and translation; and 4) genes responsive to only food and food value were enriched for regulation of neuronal signaling. These results reveal how activities necessary for colony survival are channeled through the reward system of individual honey bees.

}, issn = {1601-183X}, doi = {10.1111/gbb.12275}, author = {McNeill, Matthew S and Kapheim, Karen M and Brockmann, Axel and McGill, Tara A W and Robinson, Gene E} } @article {16569, title = {Butterflies (Lepidoptera) of the Kameng Protected Area Complex, western Arunachal Pradesh, India}, journal = {Journal of Threatened Taxa}, volume = {8}, year = {2016}, pages = {9053{\textendash}9124}, author = {Sondhi, S. and Kunte, Krushnamegh} } @article {8327, title = {Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention}, journal = {Stem Cells Int}, year = {2016}, month = {08/2016}, abstract = {

Radiation is the most potent mode of cancer therapy; however, resistance to radiation therapy results in tumor relapse and subsequent fatality. The cancer stem cell (CSC), which has better DNA repair capability, has been shown to contribute to tumor resistance and is an important target for treatment. Signaling molecules such as Notch, Wnt, and DNA repair pathways regulate molecular mechanisms in CSCs; however, none of them have been translated into therapeutic targets. The RhoGTPases and their effector ROCK-signaling pathway, though important for tumor progression, have not been well studied in the context of radioresistance. There are reports that implicate RhoA in radioresistance. ROCK2 has also been shown to interact with BRCA2 in the regulation of cell division. Incidentally, statins (drug for cardiovascular ailment) are functional inhibitors of RhoGTPases. Studies suggest that patients on statins have a better prognosis in cancers. Data from our lab suggest that ROCK signaling regulates radioresistance in cervical cancer cells. Collectively, these findings suggest that Rho/ROCK signaling may be important for radiation resistance. In this review, we enumerate the role of Rho/ROCK signaling in stemness and radioresistance and highlight the need to explore these molecules for a better understanding of radioresistance and development of therapeutics.

}, author = {Pranatharthi, A. and Ross, C. and Srivastava, S} } @article {11604, title = {Capturing the Membrane-Triggered Conformational Transition of an α-Helical Pore-Forming Toxin.}, journal = {J Phys Chem B}, volume = {120}, year = {2016}, month = {2016 Dec 01}, pages = {12064-12078}, abstract = {

Escherichia coli cytolysin A (ClyA) is an α-helical pore-forming toxin (PFT) which lyses target cells by forming membrane permeabilizing pores. The rate-determining step of this process is the conversion of the soluble ClyA monomer into a membrane inserted protomer. We elucidate the mechanism of this conformational transition using molecular dynamics simulations of coarse-grained models of ClyA and a membrane. We find that a membrane is necessary for the conformational conversion because membrane-protein interactions counteract the loss of the many intraprotein hydrophobic interactions that stabilize the membrane-inserting segments in the ClyA monomer. Of the two membrane-inserting segments, the flexible and highly hydrophobic β-tongue inserts first while the insertion of helix αA1 is membrane assisted. We conclude that the β-tongue is designed to behave as a quick-response membrane sensor, while helix αA1 improves target selectivity for cholesterol-containing cell membranes by acting as a fidelity check.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.6b09400}, author = {Giri Rao, V V Hemanth and Desikan, Rajat and Ayappa, K Ganapathy and Gosavi, Shachi} } @article {3562, title = {CD66 and CD49f expressing cells are associated with distinct neoplastic phenotypes and progression in human cervical cancer.}, journal = {Eur J Cancer}, volume = {60}, year = {2016}, month = {2016 Apr 28}, pages = {166-178}, abstract = {

BACKGROUND: In this study, building on our recent work identifying a subset of CD66+ve cells with distinctive tumourigenic properties in human cervical cancers, we examine patterns of expression and function of these cells; to generate insights into the process of metastasis.

METHODS: Our broad approach in this study has been to compare the expression and function of two subsets marked by CD66 and CD49f. We use a combination of histopathology, immunostaining and flow cytometry, functional analysis of an established cervical cancer cell line and a retrospective analysis of a cohort of cervical cancer.

RESULTS: We noted CD66 expression associated with clusters of cells which are spindle shaped, SMA+ve, podoplanin+ve, phalloidin high, fibronectin high, plakoglobin low, ki67-ve and CK10+ve at the migratory phase along with features of partial EMT. Further, TGFβ1 a well known regulator of EMT, positively correlated with CD66 expression. The additional CD49f+ve subset at the leading invading front of migration was SMA-ve, phalloidin low, fibronectin low, plakoglobin high, Ki67+ve and CK14+ve. These data are consistent with a role for CD66 cells in metastatic invasion with a collective cell migration process co-opting the CD49f subset. Our retrospective analysis of a cohort is consistent with a role for CD66 in metastasis. However, the broad analysis of CD66, CD49f and TGFβ1 expression with patterns of overall survival points to a possible protective effect particularly for local recurrences. Hence, future studies focussing on potential heterogeneity within the CD66 subset\ along with the possible role of isoforms and intra-cellular roles would be essential.

}, issn = {1879-0852}, doi = {10.1016/j.ejca.2016.03.072}, author = {Ammothumkandy, Aswathy and Maliekal, Tessy Thomas and Bose, Mayil Vahanan and Rajkumar, Thangarajan and Shirley, Sundersingh and Thejaswini, B and Giri, Venkat G and Krishna, Sudhir} } @article {3570, title = {Choice and destiny: the substrate composition and mechanical stability of settlement structures can mediate coral recruit fate in post-bleached reefs}, journal = {Coral Reefs}, volume = {35}, year = {2016}, month = {March 2016}, pages = {211-222}, abstract = {

Increasingly frequent and intense ocean warming events seriously test the buffer and recovery capacities of tropical coral reefs. Post-disturbance, available settlement structures on a reef (often dead coral skeletons) vary considerably in their mechanical stability and substrate composition, critically influencing coral recruit settlement choice and fate. In the wake of a coral mass mortality in the Lakshadweep archipelago, we examine (1) the relative availability of recruit settlement structures (from stable to unstable: reef platform, dead massive coral, consolidated rubble, dead corymbose coral, dead tabular coral, and unconsolidated rubble) in 12 recovering reefs across three atolls in the archipelago, (2) the substrate composition [crustose coralline algae (CCA), mixed turf, macroalgae] of these structural forms, and (3) whether the choice and fate of young coral are mediated by the substrate and stability of different structural forms. For this, we measured the abundance and distribution of recruit (\<1 cm), juvenile (1{\textendash}5 cm), and young adult (5{\textendash}10) corals of 24 common coral genera. Four years after the mass mortality, reefs differed considerably in composition of settlement structures. The structures themselves varied significantly in substrate cover with dead tables largely covered in CCA [60 {\textpm} 6.05 \% (SE)] and dead corymbose coral dominated by mixed turf (61.83 {\textpm} 3.8 \%). The youngest visible recruits (\<1 cm) clearly preferred CCA-rich structures such as dead massives and tables. However, older size classes were rarely found on unstable structures (strongly {\textquotedblleft}avoiding{\textquotedblright} tables, Ivlev{\textquoteright}s electivity index, E = -0.5). Our results indicate that while substrate cover might mediate coral choice, the mechanical stability of settlement structures is critical in determining post-settlement coral survival. The composition and availability of settlement structures on a reef may serve as a characteristic signature of its recovery potential, aiding in assessments of reef resilience.

}, doi = {10.1007/s00338-015-1358-z}, url = {http://link.springer.com/article/10.1007\%2Fs00338-015-1358-z}, author = {Yadav, Shreya and Rathod, Pooja and Alcoverro, Teresa and Arthur, Rohan} } @article {8203, title = {Chronic but not acute immobilization stress stably enhances hippocampal CA1 metabotropic glutamate receptor dependent Long-Term Depression.}, journal = {Neurosci Lett}, volume = {633}, year = {2016}, month = {2016 Sep 20}, pages = {101-105}, abstract = {

Acute stress has been shown to facilitate but not increase metabotropic glutamate receptor (mGluR) mediated Long-Term Depression (LTD) in the hippocampus. However, the effect of chronic stress on mGluR dependent LTD has not been investigated. Moreover, whether stress leads to a transient modification LTD threshold or a more stable change in synaptic plasticity needs to be addressed. In the present study, we have explored the effects of both a ten-day long and a single day immobilization stress protocol on mGluR-LTD at the CA3:CA1synapse in the hippocampus of adult male Sprague-Dawley rats, a day after applying stress. Bath application of the selective group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) promoted robust LTD in hippocampal slices from control (i.e. un-stressed) animals. Administration of immobility stress for two hours per day for ten days significantly elevated this LTD to a level almost twice that of control, when observed 24h following the last stress event. Acute stress i.e. a single day of two hours of immobilization, however, failed to significantly enhance LTD, 24h later. These results demonstrate for the first time, that repeated exposure to stress, but not a single stress event, is required to bring about a stable alteration in mGluR mediated synaptic plasticity.

}, issn = {1872-7972}, doi = {10.1016/j.neulet.2016.09.031}, author = {Sengupta, Tathagata and Das, Rishi and Chattarji, Sumantra} } @article {8204, title = {The cicadas (Hemiptera: Cicadidae) of India, Bangladesh, Bhutan, Myanmar, Nepal and Sri Lanka: an annotated provisional catalogue, regional checklist and bibliography.}, journal = {Biodivers Data J}, year = {2016}, month = {2016}, pages = {e8051}, abstract = {

BACKGROUND: The cicadas of the Indian subcontinent, like many other insects in the region, have remained understudied since the early part of the 20th Century, and await modern taxonomic, systematic and phylogenetic treatment. This paper presents an updated systematic catalogue of cicadas (Hemiptera: Cicadidae) from India, Bangladesh, Bhutan, Myanmar, Nepal and Sri Lanka, the first in over a century.

NEW INFORMATION: This paper treats 281 species, including: India and Bangladesh (189 species), Bhutan (19 species), Myanmar (81 species), Nepal (46 species) and Sri Lanka (22 species). For each species all recognized junior synonyms are included with information on the type material and additional specimens where relevant. The global distributional range and notes on the taxonomy of each species are included where appropriate. Two lists are provided: (1) species known to occur in India and Bangladesh (treated as a geographic unit), Bhutan, Myanmar, Nepal and Sri Lanka; and (2) species previously listed from these countries in error. A bibliography of species descriptions is provided, with the papers containing the original descriptions provided where copyright allows.

}, issn = {1314-2828}, doi = {10.3897/BDJ.4.e8051}, author = {Price, Benjamin Wills and Allan, Elizabeth Louise and Marathe, Kiran and Sarkar, Vivek and Simon, Chris and Kunte, Krushnamegh} } @article {3551, title = {Cloning, expression, purification, crystallization and initial crystallographic analysis of FleN from Pseudomonas aeruginosa.}, journal = {Acta Crystallogr F Struct Biol Commun}, volume = {72}, year = {2016}, month = {2016 Feb 1}, pages = {135-8}, abstract = {

The assembly of bacterial flagella requires the coordinated expression of a large number of genes in a hierarchical manner. These genes code for structural components of flagella, regulatory components and components that are required for chemotaxis. Stringent spatial and numerical control of flagella biosynthesis is essential for promoting motility and pathogenesis in bacteria. These genes are regulated at the level of transcription. FleN, a P-loop-containing ATPase, plays an important role in maintaining flagellar number in Pseudomonas aeruginosa. FleN exhibits anti-activator activity against FleQ, the global transcriptional regulator of flagellar genes. In order to gain insights into the regulatory mechanism of flagella synthesis, full-length FleN was crystallized in complex with the nonhydrolyzable ATP analogue β,γ-imidoadenosine 5{\textquoteright}-triphosphate (AMPPNP) in space group C2221, with unit-cell parameters a = 49.1, b = 206.9, c = 103.3 {\r A}. The Matthews coefficient is 2.19 {\r A}(3) Da(-1) assuming the presence of two molecules in the asymmetric unit, and the corresponding solvent content is 43.7\%. X-ray diffraction data were collected to a minimum Bragg spacing of 2.21 {\r A} and crystals of FleN-AMPPNP were prepared with selenomethionine-labelled FleN for ab initio phasing.

}, issn = {2053-230X}, doi = {10.1107/S2053230X16000170}, author = {Harshita, Chanchal and Jain, Deepti} } @article {3561, title = {Comparative analyses of low, medium and high-resolution HLA typing technologies for human populations}, journal = {Journal of Clinical \& Cellular Immunology}, volume = {7}, year = {2016}, chapter = {399-406}, abstract = {

Human Leukocyte Antigen (HLA) encoding genes are part of the major histocompatibility complex (MHC) on human chromosome 6. This region is one of the most polymorphic regions in the human genome. Prior knowledge of HLA allelic polymorphisms is clinically important for matching donor and recipient during organ/tissue transplantation. HLA allelic information is also useful in predicting immune responses to various infectious diseases, genetic disorders and autoimmune conditions. India harbors over a billion people and its population is untapped for HLA allelic diversity. In this study, we explored and compared three HLA typing methods for South Indian population, using Sequence-Specific Primers (SSP), NGS (Roche/454) and single- molecule sequencing (PacBio RS II) platforms. Over 1020 DNA samples were typed at low resolution using SSP method to determine the major HLA alleles within the South Indian population. These studies were followed up with medium resolution HLA typing of 80 samples based on exonic sequences on the Roche/454 sequencing system and high-resolution (6-8 digit) typing of 8 samples for HLA alleles of class I genes (HLA-A, B and C) and class II genes (HLA-DRB1 and DQB1) using PacBio RS II platform. The long reads delivered by SMRT technology, covered the full-length class I and class II genes/alleles in contiguous reads including untranslated regions, exons and introns, which provided phased SNP information. We have identified three novel alleles from PacBio data that were verified by Roche 454 sequencing. This is the first case study of HLA typing using second and third generation NGS technologies for an Indian population. The PacBio platform is a promising platform for large-scale HLA typing for establishing an HLA database for the untapped ethnic populations of India.

}, url = {http://www.omicsonline.org/clinical-cellular-immunology-abstract.php?abstract_id=69380}, author = {Gowda, M. and Ambardar, S. and Dighe, N. and Manjunath, A. and Shankaralingu, C. and Hallappa, P. and Harting, J. and Ranade, S. and Jagannathan, L. and Krishna, S.} } @article {5304, title = {Comparative Genomics of Interreplichore Translocations in Bacteria: A Measure of Chromosome Topology?}, journal = {G3 (Bethesda)}, volume = {6}, year = {2016}, month = {2016}, pages = {1597-606}, abstract = {

Genomes evolve not only in base sequence but also in terms of their architecture, defined by gene organization and chromosome topology. Whereas genome sequence data inform us about the changes in base sequences for a large variety of organisms, the study of chromosome topology is restricted to a few model organisms studied using microscopy and chromosome conformation capture techniques. Here, we exploit whole genome sequence data to study the link between gene organization and chromosome topology in bacteria. Using comparative genomics across \~{}250 pairs of closely related bacteria we show that: (a) many organisms show a high degree of interreplichore translocations throughout the chromosome and not limited to the inversion-prone terminus (ter) or the origin of replication (oriC); (b) translocation maps may reflect chromosome topologies; and (c) symmetric interreplichore translocations do not disrupt the distance of a gene from oriC or affect gene expression states or strand biases in gene densities. In summary, we suggest that translocation maps might be a first line in defining a gross chromosome topology given a pair of closely related genome sequences.

}, issn = {2160-1836}, doi = {10.1534/g3.116.028274}, author = {Khedkar, Supriya and Seshasayee, Aswin Sai Narain} } @article {11608, title = {Computational Analysis of the Domain Architecture and Substrate-Gating Mechanism of Prolyl Oligopeptidases from Shewanella woodyi and Identification of Probable Lead Molecules.}, journal = {Interdiscip Sci}, volume = {8}, year = {2016}, month = {2016 Sep}, pages = {284-93}, abstract = {

Prolyl oligopeptidases (POPs) are serine proteases found in prokaryotes and eukaryotes which hydrolyze the peptide bond containing proline. The current study focuses on the analysis of POP sequences, their distribution and domain architecture in Shewanella woodyi, a Gram-negative, luminous bacterium which causes celiac sprue and similar infections in marine organisms. The POP undergoes huge interdomain movement, which allows possible route for the entry of any substrate. Hence, it offers an opportunity to understand the mechanism of substrate gating by studying the domain architecture and possibility to identify a probable drug target. In the present study, the POP sequence was retrieved from GenBank database and the best homologous templates were identified by PSI-BLAST search. The three-dimensional structures of the closed and open forms of POP from S. woodyi, which are not available in native form, were generated by homology modeling. The ideal lead molecules were screened by computer-aided virtual screening, and the binding potential of the best leads toward the target was studied by molecular docking. The domain architecture of the POP revealed that it has a propeller domain consists of [Formula: see text]-sheets, surrounded by [Formula: see text]-helices and [Formula: see text] hydrolase domain with catalytic triad containing Ser-564, Asp-646 and His-681. The hypothetical models of open and closed POP showed backbone RMSD value of 0.56 and 0.65\ {\r A}, respectively. Ramachandran plot of the open and closed POP conformations accounts for 99.4 and 98.7\ \% residues in the favoured region, respectively. Our study revealed that propeller domain comes as an insert between N-terminal and C-terminal [Formula: see text] hydrolase domain. Molecular docking, drug likeness properties and ADME prediction suggested that KUC-103481N and Pramiracetum can be used as probable lead molecules toward the POP from S. woodyi.

}, issn = {1867-1462}, doi = {10.1007/s12539-015-0282-9}, author = {Patil, Priya and Skariyachan, Sinosh and Mutt, Eshita and Kaushik, Swati} } @article {5216, title = {Contrasting effects of defaunation on aboveground carbon storage across the global tropics.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {11351}, abstract = {

Defaunation is causing declines of large-seeded animal-dispersed trees in tropical forests worldwide, but whether and how these declines will affect carbon storage across this biome is unclear. Here we show, using a pan-tropical data set, that simulated declines of large-seeded animal-dispersed trees have contrasting effects on aboveground carbon stocks across Earth{\textquoteright}s tropical forests. In our simulations, African, American and South Asian forests, which have high proportions of animal-dispersed species, consistently show carbon losses (2-12\%), but Southeast Asian and Australian forests, where there are more abiotically dispersed species, show little to no carbon losses or marginal gains ({\textpm}1\%). These patterns result primarily from changes in wood volume, and are underlain by consistent relationships in our empirical data (\~{}2,100 species), wherein, large-seeded animal-dispersed species are larger as adults than small-seeded animal-dispersed species, but are smaller than abiotically dispersed species. Thus, floristic differences and distinct dispersal mode-seed size-adult size combinations can drive contrasting regional responses to defaunation.

}, issn = {2041-1723}, doi = {10.1038/ncomms11351}, author = {Osuri, Anand M and Ratnam, Jayashree and Varma, Varun and Alvarez-Loayza, Patricia and Hurtado Astaiza, Johanna and Bradford, Matt and Fletcher, Christine and Ndoundou-Hockemba, Mireille and Jansen, Patrick A and Kenfack, David and Marshall, Andrew R and Ramesh, B R and Rovero, Francesco and Sankaran, Mahesh} } @article {5300, title = {Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].}, journal = {Biochem J}, volume = {473}, year = {2016}, month = {2016 Jun 15}, pages = {1681-92}, abstract = {

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes.

}, issn = {1470-8728}, doi = {10.1042/BCJ20160069}, author = {Kolay, Sourav and Basu, Urbashi and Raghu, Padinjat} } @article {11621, title = {Control of Stem Cell Fate and Function by Polymer Nanofibers}, journal = {JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY}, volume = {16}, year = {2016}, month = {09/2016}, pages = { 9015-9021}, abstract = {

Stem cells are considered as an integral part of tissue engineering and regenerative medicine. Cellular functions of stem cells, which are responsible for tissue organization, can be controlled and regulated by providing an appropriate microenvironment, which mimics native stem cell niche. Nanotechnology is a powerful tool for engineering cellular microenvironment in the form of scaffolds. The scaffolds that have nanoscale features, for example, nanofiber, are considered as an effective substratum for tissue regenerative applications because they structurally mimic the native extracellular matrix (ECM). Electrospinning is a technique which produces polymer nanofiber scaffolds with controlled size and orientation of the fibrous structure. These polymer nanofibers can be used to control stem cell fate and function, in particular cell adhesion, proliferation and differentiation, during tissue engineering. In this article, we focus on recent developments and research trends in polymer nanofibrous scaffolds and their impact in controlling and regulating stem cell fate and function.

}, doi = {10.1166/jnn.2016.12735}, author = {Rana, Deepti and Leena, Maria and Nithyananth, Manasseh and Pasricha, Renu and Manivasagam, Geetha and Ramalingam, Murugan} } @article {3544, title = {Cortical actin and the plasma membrane: inextricably intertwined.}, journal = {Curr Opin Cell Biol}, volume = {38}, year = {2016}, month = {2016 Feb}, pages = {81-9}, abstract = {

The plasma membrane serves as a barrier, separating the cell from its external environment. Simultaneously it acts as a site for information transduction, entry of nutrients, receptor signaling, and adapts to the shape of the cell. This requires local control of organization at multiple scales in this heterogeneous fluid lipid bilayer with a plethora of proteins and a closely juxtaposed dynamic cortical cytoskeleton. New membrane models highlight the influence of the underlying cortical actin on the diffusion of membrane components. Myosin motors as well as proteins that remodel actin filaments have additionally been implicated in defining the organization of many membrane constituents. Here we provide a perspective of the intimate relationship of the membrane lipid matrix and the underlying cytoskeleton.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2016.02.021}, author = {K{\"o}ster, Darius V and Mayor, Satyajit} } @article {9605, title = {The delayed strengthening of synaptic connectivity in the amygdala depends on NMDA receptor activation during acute stress.}, journal = {Physiol Rep}, volume = {4}, year = {2016}, month = {2016 Oct}, abstract = {

There is growing evidence that stress leads to contrasting patterns of structural plasticity in the hippocampus and amygdala, two brain areas implicated in the cognitive and affective symptoms of stress-related psychiatric disorders. Acute stress has been shown to trigger a delayed increase in the density of dendritic spines in the basolateral amygdala (BLA) of rodents. However, the physiological correlates of this delayed spinogenesis in the BLA remain unexplored. Furthermore, NMDA receptors (NMDARs) have been known to underlie chronic stress-induced structural plasticity in the hippocampus, but nothing is known about the role of these receptors in the delayed spinogenesis, and its physiological consequences, in the BLA following acute stress. Here, using whole-cell recordings in rat brain slices, we find that a single exposure to 2-h immobilization stress enhances the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs) recorded from principal neurons in the BLA 10\ days later. This was also accompanied by faster use-dependent block of NMDA receptor currents during repeated stimulation of thalamic inputs to the BLA, which is indicative of higher presynaptic release probability at these inputs 10\ days later. Furthermore, targeted in\ vivo infusion of the NMDAR-antagonist APV into the BLA during the acute stress prevents the increase in mEPSC frequency and spine density 10\ days later. Together, these results identify a role for NMDARs during acute stress in both the physiological and morphological strengthening of synaptic connectivity in the BLA in a delayed fashion. These findings also raise the possibility that activation of NMDA receptors during stress may serve as a common molecular mechanism despite the divergent patterns of plasticity that eventually emerge after stress in the amygdala and hippocampus.

}, issn = {2051-817X}, doi = {10.14814/phy2.13002}, author = {Yasmin, Farhana and Saxena, Kapil and McEwen, Bruce S and Chattarji, Sumantra} } @article {3567, title = {Determiants of dry season habitat use by Asian elephants in the Western Ghats of India}, journal = {Journal of Zoological}, volume = {298}, year = {2016}, month = {March 2016}, pages = {169{\textendash}177}, abstract = {

Large herbivores respond to seasonal changes in resource availability through habitat selection. Understanding variations in habitat choice is crucial for targeting conservation efforts, particularly for endangered, wide-ranging species, such as the Asian elephant. We assessed patterns and determinants of elephant habitat use during the dry season, a period of resource limitation in tropical deciduous forests, in the Western Ghats of Karnataka, India. We collected detection/non-detection data on elephant signs under an occupancy sampling framework, using spatially replicated surveys on foot along forest trails to estimate probabilities of habitat use by elephants. Each of our 97 sites (sampling units) was a grid cell of 11.75 km2 area. Data were analysed using an occupancy model, which estimated detection probabilities for signs, while explicitly addressing the potential spatial dependence between sign detections on adjacent replicates. Using covariates that are likely to influence resource use, we made ecological predictions about dry season habitat use by elephants across the study area of 1850 km2. The site-level probabilities of habitat use by elephants ranged from inline image The estimated replicate level detection probability was inline image We found that distance to rivers was the best predictor of elephant habitat use, in dry season, demonstrating the overarching importance of riparian habitats in the landscape for the species. Artificial water holes established by wildlife managers do not appear to influence elephant habitat use, which is likely a result of abundant and near-uniform distribution of such water holes across the study area. The sign survey-based occupancy modelling approach provides a basis for reliable cost-effective assessment of spatial distribution and habitat use by elephants and other large herbivores. Such assessments are essential for effective conservation management of large herbivores.

}, doi = {10.1111/jzo.12298}, url = {http://onlinelibrary.wiley.com/doi/10.1111/jzo.12298/abstract}, author = {Lakshminarayanan, N. and Karanth, K.K. and Goswami, V.R. and Vaidyanathan, S. and Karanth, Ullas} } @article {11618, title = { Divergent immune priming responses across flour beetle life stages and populations }, journal = { ECOLOGY AND EVOLUTION }, volume = {6}, year = {2016}, month = {11/2016}, pages = {7847-7855}, abstract = {

Growing evidence shows that low doses of pathogens may prime the immune response in many insects, conferring subsequent protection against infection in the same developmental stage (within-life stage priming), across life stages (ontogenic priming), or to offspring (transgenerational priming). Recent work also suggests that immune priming is a costly response. Thus, depending on host and pathogen ecology and evolutionary history, tradeoffs with other fitness components may constrain the evolution of priming. However, the relative impacts of priming at different life stages and across natural populations remain unknown. We quantified immune priming responses of 10 natural populations of the red flour beetle Tribolium castaneum, primed and infected with the natural insect pathogen Bacillus thuringiensis. We found that priming responses were highly variable both across life stages and populations, ranging from no detectable response to a 13-fold survival benefit. Comparing across stages, we found that ontogenic immune priming at the larval stage conferred maximum protection against infection. Finally, we found that various forms of priming showed sex-specific associations that may represent tradeoffs or shared mechanisms. These results indicate the importance of sex-, life stage-, and population-specific selective pressures that can cause substantial divergence in priming responses even within a species. Our work highlights the necessity of further work to understand the mechanistic basis of this variability.

}, doi = {10.1002/ece3.2532}, author = {Khan, Imroze and Prakash, Arun and Agashe, Deepa} } @article {11601, title = {Divergent morphological and acoustic traits in sympatric communities of Asian barbets.}, journal = {R Soc Open Sci}, volume = {3}, year = {2016}, month = {2016 Aug}, pages = {160117}, abstract = {

The opposing effects of environmental filtering and competitive interactions may influence community assembly and coexistence of related species. Competition, both in the domain of ecological resources, and in the sensory domain (for example, acoustic interference) may also result in sympatric species evolving divergent traits and niches. Delineating these scenarios within communities requires understanding trait distributions and phylogenetic structure within the community, as well as patterns of trait evolution. We report that sympatric assemblages of Asian barbets (frugivorous canopy birds) consist of a random phylogenetic sample of species, but are divergent in both morphological and acoustic traits. Additionally, we find that morphology is more divergent than expected under Brownian evolution, whereas vocal frequency evolution is close to the pattern expected under Brownian motion (i.e. a random walk). Together, these patterns are consistent with a role for competition or competitive exclusion in driving community assembly. Phylogenetic patterns of morphological divergence between related species suggest that these traits are key in species coexistence. Because vocal frequency and size are correlated in barbets, we therefore hypothesize that frequency differences between sympatric barbets are a by-product of their divergent morphologies.

}, doi = {10.1098/rsos.160117}, author = {Krishnan, Anand and Tamma, Krishnapriya} } @article {7042, title = {Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca(2+) signalling in glutamatergic interneurons.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016 Aug 5}, abstract = {

Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR. We further show that IP3R-dependent calcium transients in the glutamatergic neurons convey this signal to downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges at the ring gland and regulates expression of ecdysteroid biosynthetic genes. Activity in this circuit is thus likely to be an adaptation that provides a layer of regulation to help surpass nutritional stress during development.

}, issn = {2050-084X}, doi = {10.7554/eLife.17495}, author = {Jayakumar, Siddharth and Richhariya, Shlesha and Reddy, O Venkateswara and Texada, Michael J and Hasan, Gaiti} } @article {3542, title = {The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites.}, journal = {Biochem Soc Trans}, volume = {44}, year = {2016}, month = {2016 Apr 15}, pages = {447-51}, abstract = {

Several recent studies have demonstrated the existence of membrane contact sites (MCS) between intracellular organelles in eukaryotic cells. Recent exciting studies have also demonstrated the existence of biomolecular interactions at these contact sites in mediating changes in the membrane composition of the cellular compartments. However, the role of such contact sites in regulating organelle function and physiological processes remains less clear. In this review we discuss the existence of a contact site between the plasma membrane (PM) and the endoplasmic reticulum (ER) inDrosophilaphotoreceptors. Further, we discuss the role of specific proteins present at this location in regulating phospholipid turnover and its impact in regulating a physiological process, namely phototransduction.

}, issn = {1470-8752}, doi = {10.1042/BST20150256}, author = {Yadav, Shweta and Cockcroft, Shamshad and Raghu, Padinjat} } @article {11592, title = {Dysregulation of mRNA Localization and Translation in Genetic Disease.}, journal = {J Neurosci}, volume = {36}, year = {2016}, month = {2016 Nov 09}, pages = {11418-11426}, abstract = {

RNA-binding proteins (RBPs) acting at various steps in the post-transcriptional regulation of gene expression play crucial roles in neuronal development and synaptic plasticity. Genetic mutations affecting several RBPs and associated factors lead to diverse neurological symptoms, as characterized by neurodevelopmental and neuropsychiatric disorders, neuromuscular and neurodegenerative diseases, and can often be multisystemic diseases. We will highlight the physiological roles of a few specific proteins in molecular mechanisms of cytoplasmic mRNA regulation, and how these processes are dysregulated in genetic disease. Recent advances in computational biology and genomewide analysis, integrated with diverse experimental approaches and model systems, have provided new insights into conserved mechanisms and the shared pathobiology of mRNA dysregulation in disease. Progress has been made to understand the pathobiology of disease mechanisms for myotonic dystrophy, spinal muscular atrophy, and fragile X syndrome, with broader implications for other RBP-associated genetic neurological diseases. This gained knowledge of underlying basic mechanisms has paved the way to the development of therapeutic strategies targeting disease mechanisms.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.2352-16.2016}, author = {Wang, Eric T and Taliaferro, J Matthew and Lee, Ji-Ann and Sudhakaran, Indulekha P and Rossoll, Wilfried and Gross, Christina and Moss, Kathryn R and Bassell, Gary J} } @article {5295, title = {Early hippocampal volume loss as a marker of eventual memory deficits caused by repeated stress.}, journal = {Sci Rep}, volume = {6}, year = {2016}, month = {2016}, pages = {29127}, abstract = {

Exposure to severe and prolonged stress has detrimental effects on the hippocampus. However, relatively little is known about the gradual changes in hippocampal structure, and its behavioral consequences, over the course of repeated stress. Behavioral analyses during 10 days of chronic stress pointed to a delayed decline in spatial memory, the full impact of which is evident only after the end of stress. In contrast, concurrent volumetric measurements in the same animals revealed significant reduction in hippocampal volumes in stressed animals relative to their unstressed counterparts, as early as the third day of stress. Notably, animals that were behaviorally the worst affected at the end of chronic stress suffered the most pronounced early loss in hippocampal volume. Together, these findings support the view that not only is smaller hippocampal volume linked to stress-induced memory deficits, but it may also act as an early risk factor for the eventual development of cognitive impairments seen in stress-related psychiatric disorders.

}, issn = {2045-2322}, doi = {10.1038/srep29127}, author = {Rahman, Mohammed Mostafizur and Callaghan, Charlotte K and Kerskens, Christian M and Chattarji, Sumantra and O{\textquoteright}Mara, Shane M} } @article {3549, title = {Editorial overview: Folding and binding: Dynamic conformational heterogeneity is pivotal to cell life.}, journal = {Curr Opin Struct Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {iv-vi}, issn = {1879-033X}, doi = {10.1016/j.sbi.2016.01.012}, author = {Nussinov, Ruth and Udgaonkar, Jayant B} } @article {8355, title = {Effects of nutrient addition and soil drainage on germination of N-fixing and non-N-fixing tropical dry forest tree species }, journal = {Plant Ecology}, volume = {217}, year = {2016}, month = {08/2016}, pages = {1043{\textendash}1054}, abstract = {

To develop generalised predictions regarding the effects of atmospheric nitrogen (N) and phosphorus (P) deposition on vegetation communities, it is necessary to account for the impacts of increased nutrient availability on the early life history stages of plants. Additionally, it is important to determine if these responses (a) differ between plant functional groups and (b) are modulated by soil drainage, which may affect the persistence of added nutrients. We experimentally assessed seed germination responses (germination proportion and germination energy, i.e. time to germination) of commonly occurring N-fixing and non-N-fixing tropical dry forest tree species found in India to simulated N and P deposition in well-drained soils, as well as soils with impeded drainage. When soils were not allowed to drain, germination proportion declined with nutrient addition, while germination energy remained unchanged. Stronger declines in germination proportion were observed for N-fixing species. In free-draining soils, nutrient addition did not affect germination proportion in either functional group. However, we detected a trend of delayed germination with nutrient addition, especially in N-fixers. Our results suggest that nutrient deposition can lead to potential shifts in functional dominance and tree community composition of tropical dry forests in the long term through its effects on early life stages of trees, although the mechanisms underlying the observed germination responses remain unclear. Further, such effects are likely to be spatially variable across the geographic range in which tropical dry forests occur depending on soil drainage properties.

}, doi = {10.1007/s11258-016-0630-9}, author = {Varma, Varun and Iyengar, Siddharth B and Sankaran, Mahesh} } @article {8343, title = {Efficient Integration of Coupled Electrical-Chemical Systems in Multiscale Neuronal Simulations.}, journal = {Front Comput Neurosci}, volume = {10}, year = {2016}, month = {2016}, pages = {97}, abstract = {

Multiscale modeling and simulations in neuroscience is gaining scientific attention due to its growing importance and unexplored capabilities. For instance, it can help to acquire better understanding of biological phenomena that have important features at multiple scales of time and space. This includes synaptic plasticity, memory formation and modulation, homeostasis. There are several ways to organize multiscale simulations depending on the scientific problem and the system to be modeled. One of the possibilities is to simulate different components of a multiscale system simultaneously and exchange data when required. The latter may become a challenging task for several reasons. First, the components of a multiscale system usually span different spatial and temporal scales, such that rigorous analysis of possible coupling solutions is required. Then, the components can be defined by different mathematical formalisms. For certain classes of problems a number of coupling mechanisms have been proposed and successfully used. However, a strict mathematical theory is missing in many cases. Recent work in the field has not so far investigated artifacts that may arise during coupled integration of different approximation methods. Moreover, in neuroscience, the coupling of widely used numerical fixed step size solvers may lead to unexpected inefficiency. In this paper we address the question of possible numerical artifacts that can arise during the integration of a coupled system. We develop an efficient strategy to couple the components comprising a multiscale test problem in neuroscience. We introduce an efficient coupling method based on the second-order backward differentiation formula (BDF2) numerical approximation. The method uses an adaptive step size integration with an error estimation proposed by Skelboe (2000). The method shows a significant advantage over conventional fixed step size solvers used in neuroscience for similar problems. We explore different coupling strategies that define the organization of computations between system components. We study the importance of an appropriate approximation of exchanged variables during the simulation. The analysis shows a substantial impact of these aspects on the solution accuracy in the application to our multiscale neuroscientific test problem. We believe that the ideas presented in the paper may essentially contribute to the development of a robust and efficient framework for multiscale brain modeling and simulations in neuroscience.

}, issn = {1662-5188}, doi = {10.3389/fncom.2016.00097}, author = {Brocke, Ekaterina and Bhalla, Upinder S and Djurfeldt, Mikael and Hellgren Kotaleski, Jeanette and Hanke, Michael} } @article {11611, title = {Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs.}, journal = {Proc Natl Acad Sci U S A}, year = {2016}, month = {2016 Oct 25}, abstract = {

Endocytosis of ligand-receptor complexes regulates signal transduction during development. In particular, clathrin and dynamin-dependent endocytosis has been well studied in the context of patterning of the Drosophila wing disc, wherein apically secreted Wingless (Wg) encounters its receptor, DFrizzled2 (DFz2), resulting in a distinctive dorso-ventral pattern of signaling outputs. Here, we directly track the endocytosis of Wg and DFz2 in the wing disc and demonstrate that Wg is endocytosed from the apical surface devoid of DFz2 via a dynamin-independent CLIC/GEEC pathway, regulated by Arf1, Garz, and class I PI3K. Subsequently, Wg containing CLIC/GEEC endosomes fuse with DFz2-containing vesicles derived from the clathrin and dynamin-dependent endocytic pathway, which results in a low pH-dependent transfer of Wg to DFz2 within the merged and acidified endosome to initiate Wg signaling. The employment of two distinct endocytic pathways exemplifies a mechanism wherein cells in tissues leverage multiple endocytic pathways to spatially regulate signaling.

}, issn = {1091-6490}, doi = {10.1073/pnas.1610565113}, author = {Hemalatha, Anupama and Prabhakara, Chaitra and Mayor, Satyajit} } @article {11612, title = {Environmental gradients structure tropical tree assemblages at the regional scale }, journal = {JOURNAL OF VEGETATION SCIENCE }, volume = {27}, year = {2016}, month = {11/2016}, pages = {1117-1128}, abstract = {

Questions: Environmental filtering and niche differences influence assembly of tree communities at multiple spatial scales. At regional scales, determining the environmental variables that primarily influence compositional variation in species assemblages reveals ecologically relevant habitat types for conservation. Strength of species{\textquoteright} association with these habitats and differences in species occurrence along environmental gradients lend credence to niche-based assembly and help estimate responses of tree communities to natural or human-mediated environmental change.

}, doi = {10.1111/jvs.12438}, author = {KKrishnadas, Meghna and Kumar, Ajith and Comita, Liza S.} } @article {3565, title = {Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.}, journal = {J Ethnopharmacol}, volume = {182}, year = {2016}, month = {2016 Apr 22}, pages = {101-9}, abstract = {

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities.

MATERIALS AND METHODS: Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection.

RESULTS: CP induced a significant decrease in testicular weight (p\<0.01) and depletion of germ cells (p\<0.001) and higher level of DNA damage (p\<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p\<0.001), DNA damage (p\<0.001) and apoptosis (p\<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner.

CONCLUSION: MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation.

}, issn = {1872-7573}, doi = {10.1016/j.jep.2016.02.003}, author = {Nayak, Guruprasad and Honguntikar, Sachin D and Kalthur, Sneha Guruprasad and D{\textquoteright}Souza, Antony Sylvan and Mutalik, Srinivas and Setty, Manjunath M and Kalyankumar, Raksha and Krishnamurthy, Hanumanthappa and Kalthur, Guruprasad and Adiga, Satish Kumar} } @article {3568, title = {First record of a bat from the Lakshadweep archipelago, southwestern India}, journal = {Mammalia}, volume = {80}, year = {2016}, month = {March 2016}, pages = {223-225}, abstract = {

he first record of a bat species from the Lakshadweep archipelago (India) has been identified as Tadarida aegyptiaca (Chiroptera: Molossidae). It appears unlikely that any bat colony may have been resident on the islands. Stranding during migration, high aerial foraging, or disorientation by wind farms on the west coast of mainland India, are factors that need to be further explored to explain this occurrence

}, doi = {10.1515/mammalia-2014-0119,}, url = {http://www.degruyter.com/view/j/mamm.ahead-of-print/mammalia-2014-0119/mammalia-2014-0119.xml}, author = {Deshpande, Kadambari. and Gangal, Mayuresh and Kelkar, Nachiket} } @article {16567, title = {Flower specialization of butterflies and impacts of non-native flower use in a transformed tropical landscape}, journal = {Biological Conservation}, volume = {201}, year = {2016}, month = {2016}, pages = {84{\textendash}191}, author = {Jain, A. and Kunte, Krushnamegh and Webb, E.L.} } @article {11609, title = { For traditional island communities in the Nicobar archipelago, complete no-go areas are the most effective form of marine management }, journal = { OCEAN \& COASTAL MANAGEMENT }, volume = {133}, year = {2016}, month = {12/2016}, pages = {53-63}, abstract = {

The ability of local communities to sustainably manage natural resource harvests in coral reefs ecosystem depends heavily on the strength of traditional institutions. Coastal communities have evolved a suite of restrictive practices to control marine offtake and there is considerable recent evidence of their effectiveness in protecting and enhancing resource stocks. However, traditionally imposed restrictions can vary considerably in their complexity and in their functional effectiveness. The indigenous communities of the Nicobar Islands are dependent on marine resources for sustenance, managing them with a range of traditionally imposed restrictions. These include limited entry to certain locations, closed seasons and areas, and restrictions on species, size-classes of fish and fishing methods. We tested the relative effectiveness of protection in areas managed under different traditional control regimes by comparing the abundance and biomass of targeted fish groups in managed and unmanaged areas. Our results indicate that reef sites with the strictest form of restriction essentially no-go areas had significantly higher abundance and biomass values of most functional groups of fishes compared with partially protected and control locations. In contrast, targeted food fish stocks did not differ from control locations in partially protected sites managed with even complex forms of traditional management. Ensuring that traditional harvest rules are complied is critical to the success of any management system, and our results suggest that they can be most strictly enforced in traditional no-go areas. Our work highlights the importance of critically evaluating the factors influencing traditional management systems to strengthen their ability to protect these reefs from unsustainable overharvest. (C) 2016 Elsevier Ltd. All rights reserved.

}, doi = {10.1016/j.ocecoaman.2016.09.003}, author = {Patankar, Vardhan and D{\textquoteright}Souza, Elrika and Alcoverro, Teresa and Arthur, Rohan} } @article {4892, title = {The Frequency of Internal Shine-Dalgarno-like Motifs in Prokaryotes.}, journal = {Genome Biol Evol}, volume = {8}, year = {2016}, month = {2016}, pages = {1722-33}, abstract = {

In prokaryotes, translation initiation typically depends on complementary binding between a G-rich Shine-Dalgarno (SD) motif in the 5{\textquoteright} untranslated region of mRNAs, and the 3{\textquoteright} tail of the 16S ribosomal RNA (the anti-SD sequence). In some cases, internal SD-like motifs in the coding region generate "programmed" ribosomal pauses that are beneficial for protein folding or accurate targeting. On the other hand, such pauses can also reduce protein production, generating purifying selection against internal SD-like motifs. This selection should be stronger in GC-rich genomes that are more likely to harbor the G-rich SD motif. However, the nature and consequences of selection acting on internal SD-like motifs within genomes and across species remains unclear. We analyzed the frequency of SD-like hexamers in the coding regions of 284 prokaryotes (277 with known anti-SD sequences and 7 without a typical SD mechanism). After accounting for GC content, we found that internal SD-like hexamers are avoided in 230 species, including three without a typical SD mechanism. The degree of avoidance was higher in GC-rich genomes, mesophiles, and N-terminal regions of genes. In contrast, 54 species either showed no signature of avoidance or were enriched in internal SD-like motifs. C-terminal gene regions were relatively enriched in SD-like hexamers, particularly for genes in operons or those followed closely by downstream genes. Together, our results suggest that the frequency of internal SD-like hexamers is governed by multiple factors including GC content and genome organization, and further empirical work is necessary to understand the evolution and functional roles of these motifs.

}, issn = {1759-6653}, doi = {10.1093/gbe/evw107}, author = {Diwan, Gaurav D and Agashe, Deepa} } @article {3553, title = {Functionally Relevant Specific Packing Can Determine Protein Folding Routes.}, journal = {J Mol Biol}, volume = {428}, year = {2016}, month = {2016 Jan 29}, pages = {509-21}, abstract = {

Functional residues can modulate the folding mechanisms of proteins. In some proteins, mutations to such residues can radically change the primary folding route. Is it possible then to learn more about the functional regions of a protein by investigating just its choice of folding route? The folding and the function of the protein Escherichia coli ribonuclease H (ecoRNase-H) have been extensively studied and its folding route is known to near-residue resolution. Here, we computationally study the folding of ecoRNase-H using molecular dynamics simulations of structure-based models of increasing complexity. The differences between a model that correctly predicts the experimentally determined folding route and a simpler model that does not can be attributed to a set of six aromatic residues clustered together in a region of the protein called CORE. This clustering, which we term "specific" packing, drives CORE to fold early and determines the folding route. Both the residues involved in specific packing and their packing are largely conserved across E. coli-like RNase-Hs from diverse species. Residue conservation is usually implicated in function. Here, the identified residues either are known to bind substrate in ecoRNase-H or pack against the substrate in the homologous human RNase-H where a substrate-bound crystal structure exists. Thus, the folding mechanism of ecoRNase-H is a byproduct of functional demands upon its sequence. Using our observations on specific packing, we suggest mutations to an engineered HIV RNase-H to make its function better. Our results show that understanding folding route choice in proteins can provide unexpected insights into their function.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2015.12.014}, author = {Yadahalli, Shilpa and Gosavi, Shachi} } @article {3566, title = {Genome scale patterns of supercoiling in a bacterial chromosome.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {11055}, abstract = {

DNA in bacterial cells primarily exists in a negatively supercoiled state. The extent of supercoiling differs between regions of the chromosome, changes in response to external conditions and regulates gene expression. Here we report the use of trimethylpsoralen intercalation to map the extent of supercoiling across the Escherichia coli chromosome during exponential and stationary growth phases. We find that stationary phase E. coli cells display a gradient of negative supercoiling, with the terminus being more negatively supercoiled than the origin of replication, and that such a gradient is absent in exponentially growing cells. This stationary phase pattern is correlated with the binding of the nucleoid-associated protein HU, and we show that it is lost in an HU deletion strain. We suggest that HU establishes higher supercoiling near the terminus of the chromosome during stationary phase, whereas during exponential growth DNA gyrase and/or transcription equalizes supercoiling across the chromosome.

}, issn = {2041-1723}, doi = {10.1038/ncomms11055}, author = {Lal, Avantika and Dhar, Amlanjyoti and Trostel, Andrei and Kouzine, Fedor and Seshasayee, Aswin S N and Adhya, Sankar} } @article {11620, title = {Genome-Wide Analysis of Polyadenylation Events in Schmidtea mediterranea.}, journal = {G3 (Bethesda)}, volume = {6}, year = {2016}, month = {2016 Oct 13}, pages = {3035-3048}, abstract = {

In eukaryotes, 3{\textquoteright} untranslated regions (UTRs) play important roles in regulating posttranscriptional gene expression. The 3{\textquoteright}UTR is defined by regulated cleavage/polyadenylation of the pre-mRNA. The advent of next-generation sequencing technology has now enabled us to identify these events on a genome-wide scale. In this study, we used poly(A)-position profiling by sequencing (3P-Seq) to capture all poly(A) sites across the genome of the freshwater planarian, Schmidtea mediterranea, an ideal model system for exploring the process of regeneration and stem cell function. We identified the 3{\textquoteright}UTRs for \~{}14,000 transcripts and thus improved the existing gene annotations. We found 97 transcripts, which are polyadenylated within an internal exon, resulting in the shrinking of the ORF and loss of a predicted protein domain. Around 40\% of the transcripts in planaria were alternatively polyadenylated (ApA), resulting either in an altered 3{\textquoteright}UTR or a change in coding sequence. We identified specific ApA transcript isoforms that were subjected to miRNA mediated gene regulation using degradome sequencing. In this study, we also confirmed a tissue-specific expression pattern for alternate polyadenylated transcripts. The insights from this study highlight the potential role of ApA in regulating the gene expression essential for planarian regeneration.

}, issn = {2160-1836}, doi = {10.1534/g3.116.031120}, author = {Lakshmanan, Vairavan and Bansal, Dhiru and Kulkarni, Jahnavi and Poduval, Deepak and Krishna, Srikar and Sasidharan, Vidyanand and Anand, Praveen and Seshasayee, Aswin and Palakodeti, Dasaradhi} } @article {3548, title = {Genome-wide data reveal cryptic diversity and genetic introgression in an Oriental cynopterine fruit bat radiation.}, journal = {BMC Evol Biol}, volume = {16}, year = {2016}, month = {2016}, pages = {41}, abstract = {

BACKGROUND: The Oriental fruit bat genus Cynopterus, with several geographically overlapping species, presents an interesting case study to evaluate the evolutionary significance of coexistence versus isolation. We examined the morphological and genetic variability of congeneric fruit bats Cynopterus sphinx and C. brachyotis using 405 samples from two natural contact zones and 17 allopatric locations in the Indian subcontinent; and investigated the population differentiation patterns, evolutionary history, and the possibility of cryptic diversity in this species pair.

RESULTS: Analysis of microsatellites, cytochrome b gene sequences, and restriction digestion based genome-wide data revealed that C. sphinx and C. brachyotis do not hybridize in contact zones. However, cytochrome b gene sequences and genome-wide SNP data helped uncover a cryptic, hitherto unrecognized cynopterine lineage in northeastern India coexisting with C. sphinx. Further analyses of shared variation of SNPs using Patterson{\textquoteright}s D statistics suggest introgression between this lineage and C. sphinx. Multivariate analyses of morphology using genetically classified grouping confirmed substantial morphological overlap between C. sphinx and C. brachyotis, specifically in the high elevation contact zones in southern India.

CONCLUSION: Our results uncover novel diversity and detect a pattern of genetic introgression in a cryptic radiation of bats, demonstrating the complicated nature of lineage diversification in this poorly understood taxonomic group. Our results highlight the importance of genome-wide data to study evolutionary processes of morphologically similar species pairs. Our approach represents a significant step forward in evolutionary research on young radiations of non-model species that may retain the ability of interspecific gene flow.

}, issn = {1471-2148}, doi = {10.1186/s12862-016-0599-y}, author = {Chattopadhyay, Balaji and Garg, Kritika M and Kumar, A K Vinoth and Doss, D Paramanantha Swami and Rheindt, Frank E and Kandula, Sripathi and Ramakrishnan, Uma} } @article {6134, title = {Genome-Wide Prediction and Analysis of 3D-Domain Swapped Proteins in the Human Genome from Sequence Information.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0159627}, abstract = {

3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78\% (85.6\% of sensitivity, 87.5\% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44\% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0159627}, author = {Upadhyay, Atul Kumar and Sowdhamini, Ramanathan} } @article {3606, title = {A genome-wide resource for the analysis of protein localisation in Drosophila.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016}, abstract = {

The Drosophila genome contains \>13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts.

}, issn = {2050-084X}, doi = {10.7554/eLife.12068}, author = {Sarov, Mihail and Barz, Christiane and Jambor, Helena and Hein, Marco Y and Schmied, Christopher and Suchold, Dana and Stender, Bettina and Janosch, Stephan and Kj, Vinay Vikas and Krishnan, R T and Krishnamoorthy, Aishwarya and Ferreira, Irene Rs and Ejsmont, Radoslaw K and Finkl, Katja and Hasse, Susanne and K{\"a}mpfer, Philipp and Plewka, Nicole and Vinis, Elisabeth and Schloissnig, Siegfried and Knust, Elisabeth and Hartenstein, Volker and Mann, Matthias and Ramaswami, Mani and VijayRaghavan, K and Tomancak, Pavel and Schnorrer, Frank} } @article {8107, title = {Genome-wide survey and phylogeny of S-Ribosylhomocysteinase (LuxS) enzyme in bacterial genomes.}, journal = {BMC Genomics}, volume = {17}, year = {2016}, month = {2016}, pages = {742}, abstract = {

BACKGROUND: The study of survival and communication of pathogenic bacteria is important to combat diseases caused by such micro-organisms. Bacterial cells communicate with each other using a density-dependent cell-cell communication process called Quorum Sensing (QS). LuxS protein is an important member of interspecies quorum-sensing system, involved in the biosynthesis of Autoinducer-2 (AI-2), and has been identified as a drug target. Despite the above mentioned significance, their evolution has not been fully studied, particularly from a structural perspective.

RESULTS: Search for LuxS in the non-redundant database of protein sequences yielded 3106 sequences. Phylogenetic analysis of these sequences revealed grouping of sequences into five distinct clusters belonging to different phyla and according to their habitat. A majority of the neighbouring genes of LuxS have been found to be hypothetical proteins. However, gene synteny analyses in different bacterial genomes reveal the presence of few interesting gene neighbours. Moreover, LuxS gene was found to be a component of an operon in only six out of 36 genomes. Analysis of conserved motifs in representative LuxS sequences of different clusters revealed the presence of conserved motifs common to sequences of all the clusters as well as motifs unique to each cluster. Homology modelling of LuxS protein sequences of each cluster revealed few structural features unique to protein of each cluster. Analyses of surface electrostatic potentials of the homology models of each cluster showed the interactions that are common to all the clusters, as well as cluster-specific potentials and therefore interacting partners, which may be unique to each cluster.

CONCLUSIONS: LuxS protein evolved early during the course of bacterial evolution, but has diverged into five subtypes. Analysis of sequence motifs and homology models of representative members reveal cluster-specific structural properties of LuxS. Further, it is also shown that LuxS protein may be involved in various protein-protein or protein-RNA interactions, which may regulate the activity of LuxS proteins in bacteria.

}, issn = {1471-2164}, doi = {10.1186/s12864-016-3002-x}, author = {Rao, Rajas M and Pasha, Shaik Naseer and Sowdhamini, Ramanathan} } @article {3554, title = {Genome-wide survey of putative RNA-binding proteins encoded in the human proteome.}, journal = {Mol Biosyst}, volume = {12}, year = {2016}, month = {2016 Jan 26}, pages = {532-40}, abstract = {

RNA-binding proteins (RBPs) are involved in various post-transcriptional gene regulatory processes and are also functionally important members of the ribosome and the spliceosome. However, RBPs and their interactions with RNA are less well-studied in comparison to DNA-binding proteins. We have classified the existing RBP structures, available in complexes with RNA and RNA/DNA hybrids, into different structural families and created Hidden Markov Models (HMMs). These structure-centric family HMMs, along with the sequence-centric family HMMs, were used as a primary database to systematically search the human proteome for the presence of putative RBPs. We have found more than 2600 gene products with RBP signatures in humans, of which around 28\% are likely to bind to RNA but not DNA, whereas 9\% might bind to both RNA and DNA. 11\% of them do not contain an explicit functional annotation yet. Nearly 30\% of the putative RBPs are exclusively nuclear, 15\% have known disease associations and around 30\% are enzymes. Around 40\% of the proteins identified in this study are novel and have not been reported by recent large-scale studies on human RBPs.

}, issn = {1742-2051}, doi = {10.1039/c5mb00638d}, author = {Ghosh, Pritha and Sowdhamini, R} } @article {3571, title = {Glial and neuronal Semaphorin signaling instruct the development of a functional myotopic map for Drosophila walking.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016}, abstract = {

Motoneurons developmentally acquire appropriate cellular architectures that ensure connections with postsynaptic muscles and presynaptic neurons. In Drosophila, leg motoneurons are organized as a myotopic map, where their dendritic domains represent the muscle field. Here, we investigate mechanisms underlying development of aspects of this myotopic map, required for walking. A behavioral screen identified roles for Semaphorins (Sema) and Plexins (Plex) in walking behavior. Deciphering this phenotype, we show that PlexA/Sema1a mediates motoneuron axon branching in ways that differ in the proximal femur and distal tibia, based on motoneuronal birth order. Importantly, we show a novel role for glia in positioning dendrites of specific motoneurons; PlexB/Sema2a is required for dendritic positioning of late-born motoneurons but not early-born motoneurons. These findings indicate that communication within motoneurons and between glia and motoneurons, mediated by the combined action of different Plexin/Semaphorin signaling systems, are required for the formation of a functional myotopic map.

}, issn = {2050-084X}, doi = {10.7554/eLife.11572}, author = {Syed, Durafshan Sakeena and Gowda, Swetha B M and Reddy, O Venkateswara and Reichert, Heinrich and VijayRaghavan, K} } @article {11606, title = {The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016 Oct 14}, abstract = {

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination.

}, issn = {2050-084X}, doi = {10.7554/eLife.15983}, author = {Gupta, Tripti and Kumar, Arun and Cattenoz, Pierre B and VijayRaghavan, K and Giangrande, Angela} } @article {3560, title = {GPI-anchored protein organization and dynamics at the cell surface.}, journal = {J Lipid Res}, volume = {57}, year = {2016}, month = {2016 Feb}, pages = {159-75}, abstract = {

The surface of eukaryotic cells is a multi-component fluid bilayer in which glycosylphosphatidylinositol (GPI)-anchored proteins are an abundant constituent. In this review, we discuss the complex nature of the organization and dynamics of GPI-anchored proteins at multiple spatial and temporal scales. Different biophysical techniques have been utilized for understanding this organization, including fluorescence correlation spectroscopy, fluorescence recovery after photobleaching, single particle tracking, and a number of super resolution methods. Major insights into the organization and dynamics have also come from exploring the short-range interactions of GPI-anchored proteins by fluorescence (or F{\"o}rster) resonance energy transfer microscopy. Based on the nanometer to micron scale organization, at the microsecond to the second time scale dynamics, a picture of the membrane bilayer emerges where the lipid bilayer appears inextricably intertwined with the underlying dynamic cytoskeleton. These observations have prompted a revision of the current models of plasma membrane organization, and suggest an active actin-membrane composite.

}, issn = {1539-7262}, doi = {10.1194/jlr.R062885}, author = {Saha, Suvrajit and Anilkumar, Anupama Ambika and Mayor, Satyajit} } @article {4893, title = {Host-specific, spatial and temporal variation in culturable gut bacterial communities of dragonflies}, journal = {Current Science}, volume = {110}, year = {2016}, month = {25 April 2016}, pages = {1513-1523}, abstract = {

Many microbial communities are associated with specific animal hosts, with major impacts on the ecological and evolutionary dynamics of both partners. We analysed gut microbial communities of eight dragonfly species in southern India. Adult dragonflies are generalist opportunistic predators; thus, we expected to find relatively high individual variation but low host-specific variation in their gut community composition. However, we find that each host species has a distinct gut bacterial community, with sampling location and month playing a small but significant role in shaping community structure. These patterns suggest that dragonflies either specialize on subsets of available prey, or their guts impose differential selective pressures resulting in distinct communities.

}, author = {Nair, A and Agashe, D} } @article {7040, title = {How cooperative are protein folding and unfolding transitions?}, journal = {Protein Sci}, year = {2016}, month = {2016 Aug 13}, abstract = {

A thermodynamically and kinetically simple picture of protein folding envisages only two states, native (N) and unfolded (U), separated by a single activation free energy barrier, and interconverting by cooperative two-state transitions. The folding/unfolding transitions of many proteins occur, however, in multiple discrete steps associated with the formation of intermediates, which is indicative of reduced cooperativity. Furthermore, much advancement in experimental and computational approaches has demonstrated entirely non-cooperative (gradual) transitions via a continuum of states and a multitude of small energetic barriers between the N and U states of some proteins. These findings have been instrumental towards providing a structural rationale for cooperative versus non-cooperative transitions, based on the coupling between interaction networks in proteins. The cooperativity inherent in a folding/unfolding reaction appears to be context dependent, and can be tuned via experimental conditions which change the stabilities of N and U. The evolution of cooperativity in protein folding transitions is linked closely to the evolution of function as well as the aggregation propensity of the protein. A large activation energy barrier in a fully cooperative transition can provide the kinetic control required to prevent the accumulation of partially unfolded forms, which may promote aggregation. Nevertheless, increasing evidence for barrier-less {\textquoteright}downhill{\textquoteright} folding, as well as for continuous {\textquoteright}uphill{\textquoteright} unfolding transitions, indicate that gradual non-cooperative processes may be ubiquitous features on the free energy landscape of protein folding. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.3015}, author = {Malhotra, Pooja and Udgaonkar, Jayant B} } @article {16565, title = {Identification of Complete Repertoire of Apis florea Odorant Receptors Reveals Complex Orthologous Relationships with Apis mellifera.}, journal = {Genome Biol Evol}, volume = {8}, year = {2016}, month = {2016 Sep 26}, pages = {2879-2895}, abstract = {

We developed a computational pipeline for homology based identification of the complete repertoire of olfactory receptor (OR) genes in the Asian honey bee species, Apis florea Apis florea is phylogenetically the most basal honey bee species and also the most distant sister species to the Western honey bee Apis mellifera, for which all OR genes had been identified before. Using our pipeline, we identified 180 OR genes in A. florea, which is very similar to the number of ORs identified in A. mellifera (177 ORs). Many characteristics of the ORs including gene structure, synteny of tandemly repeated ORs and basic phylogenetic clustering are highly conserved. The composite phylogenetic tree of A. florea and A. mellifera ORs could be divided into 21 clades which are in harmony with the existing Hymenopteran tree. However, we found a few nonorthologous OR relationships between both species as well as independent pseudogenization of ORs suggesting separate evolutionary changes. Particularly, a subgroup of the OR gene clade XI, which had been hypothesized to code cuticular hydrocarbon receptors showed a high number of species-specific ORs RNAseq analysis detected a total number of 145 OR transcripts in male and 162 in female antennae. Most of the OR genes were highly expressed on the female antennae. However, we detected five distinct male-biased OR genes, out of which three genes (AfOr11, AfOr18, AfOr170P) were shown to be male-biased in A. mellifera, too, thus corroborating a behavioral function in sex-pheromone communication.

}, issn = {1759-6653}, doi = {10.1093/gbe/evw202}, author = {Karpe, Snehal D and Jain, Rikesh and Brockmann, Axel and Sowdhamini, Ramanathan} } @article {1028, title = {Immunosenescence and the ability to survive bacterial infection in the red flour beetle Tribolium castaneum.}, journal = {J Anim Ecol}, volume = {85}, year = {2016}, month = {01/2016}, pages = {291-301}, abstract = {

In most animals, ageing is associated with a decline in immune function (immune senescence). However, different components of the immune system seem to age differentially, and many studies do not measure the ultimate fitness consequences of immune function after infection. Previous work shows that immune function may be traded off with other fitness components such as reproduction. It is possible that age alters the nature of these trade-offs, particularly in conjunction with factors such as gender and mating that can also affect investment in immune function. We tested the impact of age, sex and mating on post-infection survivorship in Tribolium castaneum flour beetles, as well as the components of baseline constitutive innate immunity and external (secreted) immune function in uninfected individuals. We also tested whether the reproductive ability of uninfected females is traded off with immune function (baseline innate and external immunity) and post-infection survivorship across age groups. We found that age, sex and mating significantly affected immune components and infection outcome, although the magnitude and nature of the impact varied in each case. We found that older beetles were more susceptible to infection by the pathogen Bacillus thuringiensis even though major components of the constitutive innate immune defence (antibacterial and phenoloxidase activity) remained unchanged or improved with age. Thus, these aspects of innate immunity cannot explain the observed decline in post-infection survival of older beetles. We did not find trade-offs between the reproductive ability of uninfected females and their immune function. In contrast to innate immunity, external immunity showed an overall decline with age but was also affected by sex and mating. Finally, we show that bacterial infection alters external immunity via complex interactions between age, sex and mating status. Our work uncovers novel interactions between age, sex and mating that can determine the evolution and outcome of immunosenescence by affecting the time course of relative investment in different immune and fitness components.

}, issn = {1365-2656}, doi = {10.1111/1365-2656.12433}, author = {Khan, Imroze and Prakash, Arun and Agashe, Deepa} } @article {8344, title = {An in silico approach towards the identification of novel inhibitors of the TLR-4 signaling pathway.}, journal = {J Biomol Struct Dyn}, volume = {34}, year = {2016}, month = {2016 Jun}, pages = {1345-62}, abstract = {

Precise functioning and fine-tuning of Toll-like receptor 4 (TLR4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant TLR4 activation causes excessive production of pro-inflammatory cytokines and interferons. This can result in life threatening conditions such as septic shock and other inflammatory disorders. The TRIF-related adaptor molecule (TRAM) adaptor protein is unique to the TLR4 signaling pathway and abrogation of TRAM-mediated TLR4 signaling is a promising strategy for developing therapeutics aimed at disrupting TRAM interactions with other components of the TLR4 signaling complex. The VIPER motif from the vaccinia virus-producing protein, A46 has been reported to disrupt TRAM-TLR4 interactions. We have exploited this information, in combination with homology modeling and docking approaches, to identify a potential binding site on TRAM lined by the BB loop and αC helix. Virtual screening of commercially available small molecules targeting the binding site enabled to short-list 12 small molecules to abrogate TRAM-mediated TLR4 signaling. Molecular dynamics and molecular mechanics calculations have been performed for the analysis of these receptor-ligand interactions.

}, issn = {1538-0254}, doi = {10.1080/07391102.2015.1079243}, author = {Mahita, Jarjapu and Harini, K and Rao Pichika, Mallikarjuna and Sowdhamini, Ramanathan} } @article {11622, title = {Interpreting functional effects of coding variants: challenges in proteome-scale prediction, annotation and assessment.}, journal = {Brief Bioinform}, volume = {17}, year = {2016}, month = {2016 Sep}, pages = {841-62}, abstract = {

Accurate assessment of genetic variation in human DNA sequencing studies remains a nontrivial challenge in clinical genomics and genome informatics. Ascribing functional roles and/or clinical significances to single nucleotide variants identified from a next-generation sequencing study is an important step in genome interpretation. Experimental characterization of all the observed functional variants is yet impractical; thus, the prediction of functional and/or regulatory impacts of the various mutations using in silico approaches is an important step toward the identification of functionally significant or clinically actionable variants. The relationships between genotypes and the expressed phenotypes are multilayered and biologically complex; such relationships present numerous challenges and at the same time offer various opportunities for the design of in silico variant assessment strategies. Over the past decade, many bioinformatics algorithms have been developed to predict functional consequences of single nucleotide variants in the protein coding regions. In this review, we provide an overview of the bioinformatics resources for the prediction, annotation and visualization of coding single nucleotide variants. We discuss the currently available approaches and major challenges from the perspective of protein sequence, structure, function and interactions that require consideration when interpreting the impact of putatively functional variants. We also discuss the relevance of incorporating integrated workflows for predicting the biomedical impact of the functionally important variations encoded in a genome, exome or transcriptome. Finally, we propose a framework to classify variant assessment approaches and strategies for incorporation of variant assessment within electronic health records.

}, issn = {1477-4054}, doi = {10.1093/bib/bbv084}, author = {Shameer, Khader and Tripathi, Lokesh P and Kalari, Krishna R and Dudley, Joel T and Sowdhamini, Ramanathan} } @article {11619, title = {Intracellular regulation of the insect chemoreceptor complex impacts odour localization in flying insects.}, journal = {J Exp Biol}, volume = {219}, year = {2016}, month = {2016 Nov 01}, pages = {3428-3438}, abstract = {

Flying insects are well known for airborne odour tracking and have evolved diverse chemoreceptors. While ionotropic receptors (IRs) are found across protostomes, insect odorant receptors (ORs) have only been identified in winged insects. We therefore hypothesized that the unique signal transduction of ORs offers an advantage for odour localization in flight. Using Drosophila, we found expression and increased activity of the intracellular signalling protein PKC in antennal sensilla following odour stimulation. Odour stimulation also enhanced phosphorylation of the OR co-receptor Orco in vitro, while site-directed mutation of Orco or mutations in PKC subtypes reduced the sensitivity and dynamic range of OR-expressing neurons in vivo, but not IR-expressing neurons. We ultimately show that these mutations reduce competence for odour localization of flies in flight. We conclude that intracellular regulation of OR sensitivity is necessary for efficient odour localization, which suggests a mechanistic advantage for the evolution of the OR complex in flying insects.

}, issn = {1477-9145}, doi = {10.1242/jeb.143396}, author = {Getahun, Merid N and Thoma, Michael and Lavista-Llanos, Sofia and Keesey, Ian and Fandino, Richard A and Knaden, Markus and Wicher, Dieter and Olsson, Shannon B and Hansson, Bill S} } @article {7038, title = {The Intracellular Signaling Molecule Darpp-32 Is a Marker for Principal Neurons in the Cerebellum and Cerebellum-Like Circuits of Zebrafish.}, journal = {Front Neuroanat}, volume = {10}, year = {2016}, month = {2016}, pages = {81}, abstract = {

The dopamine and cAMP regulated phosphoprotein of apparent molecular weight 32 kDa (Darpp-32) is an inhibitory subunit of protein phosphatase-1 (PP-1). Darpp-32 activity is regulated by multiple ligand-activated G-protein coupled receptors (GPCRs). This protein is coded for by the protein phosphatase-1 regulatory subunit 1b (ppp1r1b) gene. Here, we provide experimental evidence for the presence of multiple isoforms of ppp1r1b in zebrafish. We show that these isoforms are differentially expressed during development with the full-length isoform being maternally deposited. Next, with a custom polyclonal antibody generated against the full-length protein, we show that in the adult, Darpp-32 is strongly expressed in principal neurons of the cerebellum and cerebellum-like circuits. These include Purkinje neurons in the cerebellum, Type-I neurons in the optic tectum, and crest cells in the medial octavolateralis nucleus (MON). We confirmed the identity of these neurons through their colocalization with Parvalbumin 7 immunoreactivity. Darpp-32 is seen in the somata and dendrites of these neurons with faint staining in the axons. In all of these regions, Darpp-32-immunoreactive cells were in close proximity to tyrosine hydroxylase (TH) immunoreactive puncta indicating the presence of direct catecholaminergic input to these neurons. Darpp-32 immunoreactivity was seen in Purkinje neurons as early as 3 days post-fertilization (dpf) when Purkinje neurons are first specified. In sum, we show that Darpp-32, a signaling integrator, is a specific marker of principal neurons in the cerebellum and cerebellum-like circuits in zebrafish.

}, issn = {1662-5129}, doi = {10.3389/fnana.2016.00081}, author = {Robra, Lena and Thirumalai, Vatsala} } @article {5318, title = {Large mammal use of protected and community-managed lands in a biodiversity hotspot}, journal = {ANIMAL CONSERVATION}, volume = {19}, year = {2016}, month = {04/2016}, pages = {199-208}, abstract = {

In large parts of the biodiversity-rich tropics, various forest governance regimes often coexist, ranging from governmental administration to highly decentralized community management. Two common forms of such governance are protected areas, and community lands open to limited resource extraction. We studied wildlife occurrences in the north-east Indian state of Arunachal Pradesh, where the Eaglenest Wildlife Sanctuary (EWS) is situated adjacent to community lands governed by the Bugun and Sherdukpen tribes. We conducted transect-based mammal sign surveys and camera trapping for mammals (\>0.5 kg), and interviewed members of the resident tribes to understand their hunting practices and causes of wildlife declines. Interviews indicated hunting-mediated declines in the abundances of mammals such as the tiger Panthera tigris, gaur Bos gaurus and river otters Lutrogale and Aonyx species. Larger species such as B. gaurus were much more abundant within EWS than outside of it. Community-managed lands harbored smaller bodied species, including some of conservation importance such as the red panda Ailurus fulgens, clouded leopard Neofelis nebulosa and golden cat Pardofelis temminckii. Our findings show that protected areas may have important non-substitutive values but adjoining community-managed lands may also have important conservation values for a different set of species.

}, doi = {10.1111/acv.12234}, author = {Velho, N and Srinivasan, U and Singh, P and Laurance, WF} } @article {3547, title = {Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium.}, journal = {Mol Biol Evol}, year = {2016}, month = {2016 Feb 23}, abstract = {

Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae. These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.

}, issn = {1537-1719}, doi = {10.1093/molbev/msw035}, author = {Agashe, Deepa and Sane, Mrudula and Phalnikar, Kruttika and Diwan, Gaurav D and Habibullah, Alefiyah and Martinez-Gomez, Norma Cecilia and Sahasrabuddhe, Vinaya and Polachek, William and Wang, Jue and Chubiz, Lon M and Marx, Christopher J} } @article {5212, title = {Leaf traits of African woody savanna species across climate and soil fertility gradients: evidence for conservative versus acquisitive resource-use strategies}, journal = {Journal of Ecology}, year = {2016}, month = {05/2016}, author = {Benjamin J. Wigley and Jasper A. Slingsby and Sandra Diaz and William J. Bond and Herve Fritz and Corli Coetsee} } @article {5240, title = {Microsecond rearrangements of hydrophobic clusters in an initially collapsed globule prime structure formation during the folding of a small protein.}, journal = {J Mol Biol}, year = {2016}, month = {2016 Jun 28}, abstract = {

To determine how polypeptide chain collapse initiates structure formation during protein folding is a long standing goal. It has been challenging to characterize experimentally the dynamics of the polypeptide chain which lead to the formation of a compact kinetic molten globule (MG) in about a millisecond. In this study, the sub-millisecond events that occur early during the folding of monellin (MNEI) from the guanidine hydrochloride-unfolded state have been characterized using multiple fluorescence and fluorescence resonance energy transfer probes. The kinetic MG is shown to form in a non-cooperative manner from the unfolded (U) state as a result of at least three different processes happening during the first millisecond of folding. Initial chain compaction completes within the first 37μs, and further compaction occurs only after structure formation commences at a few milliseconds of folding. Transient non-native and native-like hydrophobic clusters with side-chains of certain residues buried form during the initial chain collapse, and the non-native clusters quickly disassemble. Subsequently, partial chain-desolvation occurs, leading to the formation of a kinetic MG. The initial chain compaction and subsequent chain rearrangement appear to be barrier-less processes. The two structural rearrangements within the collapsed globule appear to prime the protein for the actual folding transition.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2016.06.015}, author = {Goluguri, Rama Reddy and Udgaonkar, Jayant B} } @article {8358, title = {Modelling biome shifts in the Indian subcontinent under scenarios of future climate change }, journal = {Current Science}, volume = {111}, year = {2016}, pages = {147-156}, abstract = {

The Indian subcontinent is expected to witness significant changes in climatic conditions in the future, but the implications of such changes for future spatial distribution of different biomes in the subcontinent are unclear. We sought to understand the potential shifts in the distribution of biomes in India by 2070 under different emission scenarios, identify biomes and regions of the country that are particularly at risk from future changes in climate, and quantify uncertainties associated with the predictions. We used an ensemble classifier (random forest) to model current and potential future distribution of biomes in India for different climate trajectories under the newly developed representative concentration pathway (RCP) scenarios. Climate projections from 19 and 17 different general circulation models (GCMs) were used to predict future biome distributions in India under the RCP 4.5 and RCP 8.5 scenarios respectively. For each scenario, model outputs from different GCM projections were combined using a simple majority voting criterion. Approximately 630,000 sq. km (18\%) of the country is predicted to experience biome shifts under the RCP 8.5 scenario and 486,000 sq. km (14\%) under the RCP 4.5 scenario by 2070. Drier tropical biomes are likely to be replaced by wetter biomes, while temperate biomes are predicted to be dominated by vegetation characteristic of a warmer climate in the future. There was a high to moderate level of agreement between predictions of different GCMs. Our results suggest that biome shifts will be largely concentrated in the east-central and northern parts of the country, with tropical and subtropical dry forests, savannas, grasslands and xeric habitats particularly at risk. Future studies should focus on elucidating the responses of different vegetation sub-formations within individual biomes in order to gain a finer-scale understanding of vegetation responses to future climate change in the Indian subcontinent.

}, author = {Rasquinha, Dina N. and Sankaran, Mahesh} } @article {5917, title = {Molecular crowding causes narrowing of population heterogeneity and restricts internal dynamics in a protein}, journal = {METHODS AND APPLICATIONS IN FLUORESCENCE}, volume = {4}, year = {2016}, month = {MAR 2016}, abstract = {

Macromolecular crowding is a distinguishing property of intracellular media. Knowledge on the structure and dynamics of a protein in a crowded environment is essential for a complete understanding of its function. Reduction in intermolecular space could cause structural and functional alterations. Here, we have studied a model protein barstar to see how polyethylene glycol (PEG)-induced crowding affects its various structural states (native, unfolded and molten-globule-like) with different extents of change in conformational heterogeneity. Intramolecular distances and distance distributions were determined by time-resolved Forster resonance energy transfer from Trp53 to several acceptor sites by analysis of fluorescence decay kinetics using the Maximum Entropy Method. We observed PEG-induced narrowing of population distributions along with shifting of populations towards more compact states. Structural compactness also resulted in the slowing down of internal dynamics of the protein as revealed by fluorescence anisotropy decay kinetics of the fluorophore IAEDANS attached at several sites.

}, author = {Mondal, Samsuzzoha and Kallianpur, Mamata V and Udgaonkar, Jayant B and Krishnamoorthy, G} } @article {11623, title = {Molecular data in conjunction with morphology help resolve the Hemidactylus brookii complex (Squamata: Gekkonidae)}, journal = {ORGANISMS DIVERSITY \& EVOLUTION}, volume = {16}, year = {2016}, month = {09/2016}, pages = {659-677}, abstract = {

Molecular data are increasingly being used to resolve cryptic species complexes; however, subsequent formal species description and taxonomic revisions often remain incomplete. Given that most species are described based on morphology-based alpha taxonomy, one cannot resolve nomenclatural issues of species complexes without the aid of morphology. In this study, we examined the taxonomic status of a long-known human commensal and species complex, Hemidactylus brookii. To this end, samples of H. cf. brookii and related species were collected across India. We analyzed molecular as well as morphological data to resolve the taxonomy of this species complex. Seven deeply divergent, well-supported clades were recovered using the mitochondrial phylogeny, five of which were also retrieved in the nuclear tree. One of these consists of five morphologically distinct species of ground-dwelling Hemidactylus. The genetic distances across each clade of putative species of H. brookii sensu lato were comparable to that between morphologically distinct species of ground-dwelling Hemidactylus. Meristic characters such as number of precloacal-femoral pores, number of non-pore bearing scales interrupting the series of pored scales, dorsal pholidosis, and presence/absence of divided lamellae can be used to distinguish these putative species from each other. However, morphological characters of H. brookii sensu stricto did not correspond to any of the putative species studied. The study also revealed that the "H. brookii complex" in India includes two commensal species, Hemidactylus parvimaculatus and Hemidactylus murrayi. Furthermore, these two lineages have independently acquired adaptations that could have assisted them in exploiting human habitat. An identification key to diagnose species within this complex and rest of the Hemidactylus in India is proposed.

}, doi = {10.1007/s13127-016-0271-9}, author = {Lajmi, Aparna and Giri, Varad B and Karanth, K. Praveen} } @article {5299, title = {Molecular Dynamics Simulations and Structural Analysis to Decipher Functional Impact of a Twenty Residue Insert in the Ternary Complex of Mus musculus TdT Isoform.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0157286}, abstract = {

Insertions/deletions are common evolutionary tools employed to alter the structural and functional repertoire of protein domains. An insert situated proximal to the active site or ligand binding site frequently impacts protein function; however, the effect of distal indels on protein activity and/or stability are often not studied. In this paper, we have investigated a distal insert, which influences the function and stability of a unique DNA polymerase, called terminal deoxynucleotidyl transferase (TdT). TdT (EC:2.7.7.31) is a monomeric 58 kDa protein belonging to family X of eukaryotic DNA polymerases and known for its role in V(D)J recombination as well as in non-homologous end-joining (NHEJ) pathways. Two murine isoforms of TdT, with a length difference of twenty residues and having different biochemical properties, have been studied. All-atom molecular dynamics simulations at different temperatures and interaction network analyses were performed on the short and long-length isoforms. We observed conformational changes in the regions distal to the insert position (thumb subdomain) in the longer isoform, which indirectly affects the activity and stability of the enzyme through a mediating loop (Loop1). A structural rationale could be provided to explain the reduced polymerization rate as well as increased thermosensitivity of the longer isoform caused by peripherally located length variations within a DNA polymerase. These observations increase our understanding of the roles of length variants in introducing functional diversity in protein families in general.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0157286}, author = {Mutt, Eshita and Sowdhamini, Ramanathan} } @article {1023, title = {Molecular modelling of human 5-hydroxytryptamine receptor (5-HT2A) and virtual screening studies towards the identification of agonist and antagonist molecules.}, journal = {J Biomol Struct Dyn}, volume = {34}, year = {2016}, month = {05/2016}, pages = {952-70}, chapter = {952}, abstract = {

The serotonin receptors, also known as 5-hydroxytryptamine (5-HT) receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels found in the central and peripheral nervous systems. GPCRs have a characteristic feature of activating different signalling pathways upon ligand binding and these ligands display several efficacy levels to differentially activate the receptor. GPCRs are primary drug targets due to their central role in several signal transduction pathways. Drug design for GPCRs is also most challenging due to their inherent promiscuity in ligand recognition, which gives rise to several side effects of existing drugs. Here, we have performed the ligand interaction study using the two prominent states of GPCR, namely the active and inactive state of the 5-HT2A receptor. Active state of 5-HT2A receptor model enhances the understanding of conformational difference which influences the ligand-binding site. A 5-HT2A receptor active state model was constructed by homology modelling using active state β2-adrenergic receptor (β2-AR). In addition, virtual screening and docking studies with both active and inactive state models reveal potential small molecule hits which could be considered as agonist-like and antagonist-like molecules. The results from the all-atom molecular dynamics simulations further confirmed that agonists and antagonists interact in different modes with the receptor.

}, issn = {1538-0254}, doi = {10.1080/07391102.2015.1062802}, author = {Gandhimathi, A and Sowdhamini, R} } @article {11636, title = {The Multifaceted Roles of Molecular Dynamics Simulations in Drug Discovery.}, journal = {Curr Pharm Des}, volume = {22}, year = {2016}, month = {2016}, pages = {3585-600}, abstract = {

Discovery of new therapeutics is a very challenging, expensive and time-consuming process. With the number of approved drugs declining steadily, combined with increasing costs, a rational approach is needed to facilitate, expedite and streamline the drug discovery process. In silico methods are playing key roles in the discovery of a growing number of marketed drugs. The use of computational approaches, particularly molecular dynamics, in drug design is rapidly gaining momentum and acceptance as an essential part of the toolkit for modern drug discovery. From analysing atomistic details for explaining experimentally observed phenomena, to designing drugs with increased efficacy and specificity, the insight that such simulations can provide is generating new ideas and applications that have previously been unexplored. Here we discuss physics-based simulation methodologies and applications in drug design: from locating pockets to designing novel lead compounds, from small molecules to peptides. With developments in hardware, software and theory, the improved predictive abilities of in silico efforts are becoming an essential part of efficient, economic and accurate drug development strategies.

}, issn = {1873-4286}, author = {Fox, Stephen John and Li, Jianguo and Sing Tan, Yaw and Nguyen, Minh N and Pal, Arumay and Ouaray, Zohra and Yadahalli, Shilpa and Kannan, Srinivasaraghavan} } @article {7589, title = {Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons.}, journal = {J Cell Sci}, year = {2016}, month = {2016 Sep 2}, abstract = {

Store-operated Ca(2+) entry (SOCE) occurs when loss of Ca(2+) from the endoplasmic reticulum (ER) stimulates the Ca(2+) sensor, STIM, to cluster and activate the plasma membrane (PM) Ca(2+) channel, Orai. Inositol 1,4,5-trisphosphate receptors (IP3R) are assumed to regulate SOCE solely by mediating ER Ca(2+) release. We show that in Drosophila neurons, mutant IP3R attenuate SOCE evoked by depleting Ca(2+) stores with thapsigargin. In normal neurons, store depletion caused STIM and IP3R to accumulate near the PM, association of STIM with Orai, clustering of STIM and Orai at ER-PM junctions, and activation of SOCE. These responses were attenuated in neurons with mutant IP3R and rescued by over-expression of STIM with Orai. We conclude that after depletion of Ca(2+) stores in Drosophila, translocation of IP3R to ER-PM junctions facilitates the coupling of STIM to Orai that leads to activation of SOCE.

}, issn = {1477-9137}, doi = {10.1242/jcs.191585}, author = {Chakraborty, Sumita and Deb, Bipan K and Chorna, Tetyana and Konieczny, Vera and Taylor, Colin W and Hasan, Gaiti} } @article {3555, title = {The N(2)-Furfuryl-deoxyguanosine Adduct Does Not Alter the Structure of B-DNA.}, journal = {J Org Chem}, volume = {81}, year = {2016}, month = {2016 Jan 15}, pages = {502-11}, abstract = {

N(2)-Furfuryl-deoxyguanosine (fdG) is carcinogenic DNA adduct that originates from furfuryl alcohol. It is also a stable structural mimic of the damage induced by the nitrofurazone family of antibiotics. For the structural and functional studies of this model N(2)-dG adduct, reliable and rapid access to fdG-modified DNAs are warranted. Toward this end, here we report the synthesis of fdG-modified DNAs using phosphoramidite chemistry involving only three steps. The functional integrity of the modified DNA has been verified by primer extension studies with DNA polymerases I and IV from E. coli. Introduction of fdG into a DNA duplex decreases the Tm by \~{}1.6 {\textdegree}C/modification. Molecular dynamics simulations of a DNA duplex bearing the fdG adduct revealed that though the overall B-DNA structure is maintained, this lesion can disrupt W-C H-bonding, stacking interactions, and minor groove hydrations to some extent at the modified site, and these effects lead to slight variations in the local base pair parameters. Overall, our studies show that fdG is tolerated at the minor groove of the DNA to a better extent compared with other bulky DNA damages, and this property will make it difficult for the DNA repair pathways to detect this adduct.

}, issn = {1520-6904}, doi = {10.1021/acs.joc.5b02341}, author = {Ghodke, Pratibha P and Gore, Kiran R and Harikrishna, S and Samanta, Biswajit and Kottur, Jithesh and Nair, Deepak T and Pradeepkumar, P I} } @article {5907, title = {Neotype designation for Calotes versicolor Daudin, 1802 (Sauria: Agamidae) with notes on its systematics.}, journal = {Zootaxa}, volume = {4126}, year = {2016}, month = {2016}, pages = {271-9}, abstract = {

Calotes versicolor Daudin, 1802 is one of the most widespread agamid lizard species which was described without a locality. The type specimen of the species has long been considered lost; however most workers considered Pondicherry as the type locality for the species. Studies by Zug et al. 2006 confirmed that C. versicolor is a complex of multiple species which necessitates fixing type locality and specimen for the species in order to resolve the systematics of the species complex. An adult male from Pondicherry was collected and is here designated as the neotype. A re-description of the species is provided along with notes on systematics of the species.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4126.2.7}, author = {Gowande, Gaurang and Mishra, Anurag and Mirza, Zeeshan A} } @article {8758, title = {Neurobiology and biomechanics of flight in miniature insects.}, journal = {Curr Opin Neurobiol}, volume = {41}, year = {2016}, month = {2016 Oct 4}, pages = {158-166}, abstract = {

Miniature insects can be as small as a few hundred micrometres in size, making them among the smallest metazoan animals ever described. Yet, even at these length scales, they display remarkably sophisticated flight behaviours. For flight at such low Reynolds numbers, miniature insects have evolved biomechanical and neural adaptations that push the boundaries of what is possible in the realm of physics and neurobiology of flight. After several decades of relative dormancy, this question has recently been revisited by researchers working in diverse areas ranging from systematics and neurobiology to dispersal behaviours. In this review, I cover recent findings in this area, and point towards the many open questions that still remain unanswered.

}, issn = {1873-6882}, doi = {10.1016/j.conb.2016.09.008}, author = {Sane, Sanjay P} } @article {5308, title = {A New Miocene-Divergent Lineage of Old World Racer Snake from India.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0148380}, abstract = {

A distinctive early Miocene-divergent lineage of Old world racer snakes is described as a new genus and species based on three specimens collected from the western Indian state of Gujarat. Wallaceophis gen. et. gujaratenesis sp. nov. is a members of a clade of old world racers. The monotypic genus represents a distinct lineage among old world racers is recovered as a sister taxa to Lytorhynchus based on ~3047bp of combined nuclear (cmos) and mitochondrial molecular data (cytb, ND4, 12s, 16s). The snake is distinct morphologically in having a unique dorsal scale reduction formula not reported from any known colubrid snake genus. Uncorrected pairwise sequence divergence for nuclear gene cmos between Wallaceophis gen. et. gujaratenesis sp. nov. other members of the clade containing old world racers and whip snake is 21-36\%.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0148380}, author = {Mirza, Zeeshan A and Vyas, Raju and Patel, Harshil and Maheta, Jaydeep and Sanap, Rajesh V} } @article {8759, title = {A new species of the Cyrtodactylus (Geckoella) collegalensis (Beddome, 1870) complex (Squamata: Gekkonidae) from Western India.}, journal = {Zootaxa}, volume = {4170}, year = {2016}, month = {2016 Sep 23}, pages = {339-354}, abstract = {

A new species of Cyrtodactylus (Geckoella) from the C. collegalensis complex is described based on a series of specimens from western and central India. Morphological and molecular data support the distinctiveness of the new form, which can be diagnosed from other Cyrtodactylus (including other Geckoella) species by its small body size (snout to vent length to 56 mm), the absence of precloacal and femoral pores, no enlarged preanal or femoral scales, and a dorsal scalation consisting wholly of small, granular scales. The new species is most closely related to C. collegalensis, C. speciosus and C. yakhuna, from which it differs by the presence of a patch of enlarged roughly hexagonal scales on the canthus rostralis and beneath the angle of jaw, its relatively long limbs and narrow body, and a dorsal colour pattern of 4-6 pairs of dark spots.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4170.2.7}, author = {Agarwal, Ishan and Mirza, Zeeshan A and Pal, Saunak and Maddock, Simon T and Mishra, Anurag and Bauer, Aaron M} } @article {2214, title = {A new species of the genus Thaicharmus Kova{\v r}{\'\i}k, 1995 (Scorpiones: Buthidae) from northeast India}, journal = {Euscorpius}, volume = {215}, year = {2016}, pages = {1-11}, abstract = {

A new species Thaicharmus guptai sp. nov. is described from the northeast Indian state of Tripura. The new species differs from the known members of the genus in the following set of morphological characters: large size (total length 45.6 mm); trichobothrium d2 is distal to i1 on femur; trichobothria est, em and et on the external surface of the patella do not form a straight line. Subaculear tubercle is absent. The movable finger of pedipalp chela has 12 cutting rows of denticles. The movable finger is much longer than the pedipalp patella. Number of pectinal teeth 20/19; pectines with distinct lamellae and fulcra. Two horn-like projections are present on the ventrolateral aspect of the metasomal segment V.

}, author = {Mirza, Z.A and Sanap, R.V. and Kunte, Krushnamegh} } @article {8347, title = {New status for Fraser{\textquoteright}s forgotten Aciagrion approximans krishna, stat. nov (Odonata: Zygoptera: Coenagrionidae) from the Western Ghats of India}, journal = {International Journal of Odonatology}, volume = {19}, year = {2016}, month = {07/2016}, pages = {41-51}, chapter = {41}, abstract = {

Aciagrion Selys, 1891 is one of the taxonomically difficult and poorly known genera of Oriental damselflies. Aciargion hisopa race krishna Fraser, 1921 Fraser, F. C. (1921). A list of dragonflies from Mahableshwar. The Journal of the Bombay Natural History Society, 25, 540{\textendash}543. Retrieved from http://medusa.jcu.edu.au was described from Mahabaleshwar, Maharashtra, India. However, later Fraser (1933 Fraser, F. C. (1933). The fauna of British India, including Ceylon and Burma: Odonata (Vol. 1). London: Taylor and Francis.) doubted the taxonomic necessity of this taxon. His notion of Aciagrion hisopa (Selys, 1876) was erroneous, as evidenced by syntypes of this species in Selys{\textquoteright} collection, so the ssp. krishna is not conspecific with A. hisopa. Topotypic specimens of ssp. krishna from the Western Ghats were compared to specimens of Aciagrion approximans (Selys, 1876) from the Khasi Hills, Meghalaya, which are topotypical because of the recent designation of the neotype of this species in Selys{\textquoteright} collection. These two series were found to be very close to each other but differing at the level of subspecies, so we propose a new subspecies status and combination, Aciagrion approximans krishna Fraser, 1921 Fraser, F. C. (1921). A list of dragonflies from Mahableshwar. The Journal of the Bombay Natural History Society, 25, 540{\textendash}543. Retrieved from http://medusa.jcu.edu.au. The range and geographical variation of A. approximans beyond India is clarified.

}, doi = {10.1080/13887890.2016.1166463}, author = {Joshi, Shantanu and Kosterin, Oleg E and Kunte, Krushnamegh} } @article {11587, title = {Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae.}, journal = {Sci Rep}, volume = {6}, year = {2016}, month = {2016 Dec 19}, pages = {38840}, abstract = {

A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression in physical space, and explore the conditions for de novo biogenesis of distinct cisternae. We propose new quantitative measures that can discriminate between the various models of transport in a qualitative manner-this includes measures of the dynamics in steady state and the dynamical response to perturbations of the kind amenable to live-cell imaging.

}, issn = {2045-2322}, doi = {10.1038/srep38840}, author = {Sachdeva, Himani and Barma, Mustansir and Rao, Madan} } @article {3576, title = {Nonequilibrium phase transitions, fluctuations and correlations in an active contractile polar fluid.}, journal = {Soft Matter}, volume = {12}, year = {2016}, month = {2016 Feb 21}, pages = {2040-6}, abstract = {

We study the patterning, fluctuations and correlations of an active polar fluid consisting of contractile polar filaments on a two-dimensional substrate, using a hydrodynamic description. The steady states generically consist of arrays of inward pointing asters and show a continuous transition from a moving lamellar phase, a moving aster street, to a stationary aster lattice with no net polar order. We next study the effect of spatio-temporal athermal noise, parametrized by an active temperature TA, on the stability of the ordered phases. In contrast to its equilibrium counterpart, we find that the active crystal shows true long range order at low TA. On increasing TA, the asters dynamically remodel, concomitantly we find novel phase transitions characterized by bond-orientational and polar order upon "heating".

}, issn = {1744-6848}, doi = {10.1039/c5sm02527c}, author = {Gowrishankar, Kripa and Rao, Madan} } @article {1031, title = {Non-invasive assessment of fecal progestagens and pregnancy detection in Himalayan musk deer (Moschus~chrysogaster).}, journal = {Theriogenology}, volume = {85}, year = {2016}, month = {2016 Jan 15}, pages = {216-23}, abstract = {

The Himalayan musk deer (Moschus chrysogaster), an endangered species, is facing threat of extinction globally due to severe hunting for its musk, and efforts are under way in India to breed them in captivity. However, no information is available on the reproductive cycles of the species. In this study, we aimed to standardize an enzyme immunoassay (EIA) procedure for monitoring pregnancy using fecal samples. We collected fecal samples for 12\ months from five captive females maintained at the Musk Deer Research Centre, Bageshwar, Uttarakhand, India. Three of these females were observed mating and gave birth, whereas two were seen mating but did not give birth. The gestation periods for the three females were 183, 185, and 199\ days, respectively. High-pressure liquid chromatography revealed the presence of immunoreactive pregnanediol-3-glucuronide (PdG), progesterone, and 5α-pregnan-3α-ol-20-one (5-alpha-pregnane) metabolites in the fecal samples. We used EIAs against progesterone, PdG, and 5-alpha-pregnane to monitor pregnancy. We found PdG EIA to be a highly accurate and sensitive assay compared with the other two assays in detecting pregnancy. We conclude that PdG EIA can be used to diagnose and monitor pregnancy in Himalayan musk deer using fecal steroid analysis, at an early stage of 3\ months after mating. This study would help in conservation breeding of musk deer in captivity and in monitoring the reproductive status of the species in the wild.

}, issn = {1879-3231}, doi = {10.1016/j.theriogenology.2015.09.009}, author = {Mithileshwari, Chandrasekhar and Srivastava, Tanushree and Kumar, Vinod and Kumar, Ajith and Umapathy, Govindhaswamy} } @article {5171, title = {Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016}, abstract = {

Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1(-/-) Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation.

}, issn = {2050-084X}, doi = {10.7554/eLife.14023}, author = {Marcel, Nimi and Sarin, Apurva} } @article {3577, title = {NSDF: Neuroscience Simulation Data Format.}, journal = {Neuroinformatics}, volume = {14}, year = {2016}, month = {2016 Apr}, pages = {147-67}, abstract = {

Data interchange is emerging as an essential aspect of modern neuroscience. In the areas of computational neuroscience and systems biology there are multiple model definition formats, which have contributed strongly to the development of an ecosystem of simulation and analysis tools. Here we report the development of the Neuroscience Simulation Data Format (NSDF) which extends this ecosystem to the data generated in simulations. NSDF is designed to store simulator output across scales: from multiscale chemical and electrical signaling models, to detailed single-neuron and network models, to abstract neural nets. It is self-documenting, efficient, modular, and scalable, both in terms of novel data types and in terms of data volume. NSDF is simulator-independent, and can be used by a range of standalone analysis and visualization tools. It may also be used to store variety of experimental data. NSDF is based on the widely used HDF5 (Hierarchical Data Format 5) specification and is open, platform-independent, and portable.

}, issn = {1559-0089}, doi = {10.1007/s12021-015-9282-5}, author = {Ray, Subhasis and Chintaluri, Chaitanya and Bhalla, Upinder S and W{\'o}jcik, Daniel K} } @article {5305, title = {Observing a late folding intermediate of Ubiquitin at atomic resolution by NMR.}, journal = {Protein Sci}, year = {2016}, month = {2016 Apr 25}, abstract = {

The study of intermediates in the protein folding pathway provides a wealth of information about the energy landscape. The intermediates also frequently initiate pathogenic fibril formations. While observing the intermediates is difficult due to their transient nature, extreme conditions can partially unfold the proteins and provide a glimpse of the intermediate states. Here, we observe the high resolution structure of a hydrophobic core mutant of Ubiquitin at an extreme acidic pH by Nuclear Magnetic Resonance (NMR) spectroscopy. In the structure, the native secondary and tertiary structure is conserved for a major part of the protein. However, a long loop between the beta strands β3 and β5 is partially unfolded. The altered structure is supported by fluorescence data and the difference in free energies between the native state and the intermediate is reflected in the denaturant induced melting curves. The unfolded region includes amino acids that are critical for interaction with co-factors as well as for assembly of poly-Ubiquitin chains. The structure at acidic pH resembles a late folding intermediate of Ubiquitin and indicates that upon stabilization of the protein{\textquoteright}s core, the long loop converges on the core in the final step of the folding process. This article is protected by copyright. All rights reserved.

}, issn = {1469-896X}, doi = {10.1002/pro.2940}, author = {Surana, Parag and Das, Ranabir} } @article {5291, title = {Olfaction: Minority odors get equal say.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016}, abstract = {

The olfactory system becomes more sensitive when odor inputs are weak, and less sensitive when confronted with strong odors.

}, issn = {2050-084X}, doi = {10.7554/eLife.18037}, author = {Gupta, Priyanka and Bhalla, Upinder S} } @article {7039, title = {Orientation in high-flying migrant insects in relation to flows: mechanisms and strategies.}, journal = {Philos Trans R Soc Lond B Biol Sci}, volume = {371}, year = {2016}, month = {2016 Sep 26}, abstract = {

High-flying insect migrants have been shown to display sophisticated flight orientations that can, for example, maximize distance travelled by exploiting tailwinds, and reduce drift from seasonally optimal directions. Here, we provide a comprehensive overview of the theoretical and empirical evidence for the mechanisms underlying the selection and maintenance of the observed flight headings, and the detection of wind direction and speed, for insects flying hundreds of metres above the ground. Different mechanisms may be used-visual perception of the apparent ground movement or mechanosensory cues maintained by intrinsic features of the wind-depending on circumstances (e.g. day or night migrations). In addition to putative turbulence-induced velocity, acceleration and temperature cues, we present a new mathematical analysis which shows that {\textquoteright}jerks{\textquoteright} (the time-derivative of accelerations) can provide indicators of wind direction at altitude. The adaptive benefits of the different orientation strategies are briefly discussed, and we place these new findings for insects within a wider context by comparisons with the latest research on other flying and swimming organisms.This article is part of the themed issue {\textquoteright}Moving in a moving medium: new perspectives on flight{\textquoteright}.

}, issn = {1471-2970}, doi = {10.1098/rstb.2015.0392}, author = {Reynolds, Andy M and Reynolds, Don R and Sane, Sanjay P and Hu, Gao and Chapman, Jason W} } @article {3558, title = {PASS2 database for the structure-based sequence alignment of distantly related SCOP domain superfamilies: update to version 5 and added features.}, journal = {Nucleic Acids Res}, volume = {44}, year = {2016}, month = {2016 Jan 4}, pages = {D410-4}, abstract = {

Structure-based sequence alignment is an essential step in assessing and analysing the relationship of distantly related proteins. PASS2 is a database that records such alignments for protein domain superfamilies and has been constantly updated periodically. This update of the PASS2 version, named as PASS2.5, directly corresponds to the SCOPe 2.04 release. All SCOPe structural domains that share less than 40\% sequence identity, as defined by the ASTRAL compendium of protein structures, are included. The current version includes 1977 superfamilies and has been assembled utilizing the structure-based sequence alignment protocol. Such an alignment is obtained initially through MATT, followed by a refinement through the COMPARER program. The JOY program has been used for structural annotations of such alignments. In this update, we have automated the protocol and focused on inclusion of new features such as mapping of GO terms, absolutely conserved residues among the domains in a superfamily and inclusion of PDBs, that are absent in SCOPe 2.04, using the HMM profiles from the alignments of the superfamily members and are provided as a separate list. We have also implemented a more user-friendly manner of data presentation and options for downloading more features. PASS2.5 version is available at http://caps.ncbs.res.in/pass2/.

}, issn = {1362-4962}, doi = {10.1093/nar/gkv1205}, author = {Gandhimathi, Arumugam and Ghosh, Pritha and Hariharaputran, Sridhar and Mathew, Oommen K and Sowdhamini, R} } @article {3540, title = {The Pathogenic A116V Mutation Enhances Ion-Selective Channel Formation by Prion Protein in Membranes.}, journal = {Biophys J}, volume = {110}, year = {2016}, month = {2016 Apr 26}, pages = {1766-76}, abstract = {

Prion diseases are a group of fatal neurodegenerative disorders that afflict mammals. Misfolded and aggregated forms of the prion protein (PrP(Sc)) have been associated with many prion diseases. A transmembrane form of PrP favored by the pathogenic mutation A116V is associated with Gerstmann-Str{\"a}ussler-Scheinker syndrome, but no accumulation of PrP(Sc) is detected. However, the role of the transmembrane form of PrP in pathological processes leading to neuronal death remains unclear. This study reports that the full-length mouse PrP (moPrP) significantly increases the permeability of living cells to K(+), and forms K(+)- and Ca(2+)-selective channels in lipid membranes. Importantly, the pathogenic mutation A116V greatly increases the channel-forming capability of moPrP. The channels thus formed are impermeable to sodium and chloride ions, and are blocked by blockers of voltage-gated ion channels. Hydrogen-deuterium exchange studies coupled with mass spectrometry (HDX-MS) show that upon interaction with lipid, the central hydrophobic region (109-132) of the protein is protected against exchange, making it a good candidate for inserting into the membrane and lining the channel. HDX-MS also shows a dramatic increase in the protein-lipid stoichiometry for A116V moPrP, providing a rationale for its increased channel-forming capability. The results suggest that ion channel formation may be a possible mechanism of PrP-mediated neurodegeneration by the transmembrane forms of PrP.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2016.03.017}, author = {Sabareesan, Ambadi Thody and Singh, Jogender and Roy, Samrat and Udgaonkar, Jayant B and Mathew, M K} } @article {1169, title = {The pathogenic mutation T182A converts the prion protein into a molten globule-like conformation whose misfolding to oligomers but not to fibrils is drastically accelerated.}, journal = {Biochemistry}, volume = {55}, year = {2016}, month = {2016}, pages = {459-69}, abstract = {

Delineation of the effects of pathogenic mutations linked with familial prion diseases, on the structure and misfolding of prion protein (PrP), will be useful in understanding the molecular mechanism of PrP misfolding. Here, it has been shown that the pathogenic mutation T182A causes a drastic reduction in the apparent cooperativity and enthalpy of unfolding of the mouse prion protein (moPrP) under misfolding-prone conditions by converting the protein into a molten globule (MG)-like conformation. Hydrogen-deuterium exchange studies in conjunction with mass spectrometry indicate that the T182A mutation disrupts the core of the protein, thereby increasing overall structural dynamics. T182A moPrP is shown to misfold to oligomers very much faster than does wt moPrP, but to misfold to fibrils at a rate similar to that of wt moPrP. This observation suggests that oligomers are unlikely to play a productive role on the direct pathway of aggregation from monomer to fibrils. The observation that fully folded T182A moPrP has a MG-like structure, and that it misfolds to oligomers much faster than does wt moPrP, suggests that a MG-like intermediate, whose structure resembles that of fully folded T182A moPrP, might be populated early on the pathway of misfolding of wt moPrP to oligomers.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5b01266}, author = {Singh, Jogender and Udgaonkar, Jayant B} } @article {7079, title = {Pathogenic mutations within the disordered palindromic region of the prion protein induce structure therein and accelerate the formation of misfolded oligomers.}, journal = {J Mol Biol}, year = {2016}, month = {2016 Aug 18}, abstract = {

Little is understood about how the intrinsically disordered N-terminal region (NTR) of the prion protein modulates its misfolding and aggregation, which lead to prion disease. In this study, two pathogenic mutations, G113 V and A116 V in the palindromic region of the NTR, are shown to have no effect on the structure, stability or dynamics of native mouse prion protein (moPrP), but to nevertheless accelerate misfolding and oligomerization. For wt moPrP, misfolding and oligomerization appear to occur concurrently, while for both mutant variants, oligomerization is shown to precede misfolding. Kinetic hydrogen deuterium exchange-mass spectrometry experiments show that sequence segment 89-132 from the NTR becomes structured, albeit weakly, during the oligomerization of both mutant variants. Importantly, this structure formation occurs prior to structural conversion in the CTD, and appears to be the reason why the formation of misfolded oligomers is accelerated by the pathogenic mutations.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2016.08.015}, author = {Sabareesan, A T and Udgaonkar, Jayant B} } @article {3574, title = {Phase Segregation of Passive Advective Particles in an Active Medium.}, journal = {Phys Rev Lett}, volume = {116}, year = {2016}, month = {2016 Feb 12}, pages = {068306}, abstract = {

Localized contractile configurations or asters spontaneously appear and disappear as emergent structures in the collective stochastic dynamics of active polar actomyosin filaments. Passive particles which (un)bind to the active filaments get advected into the asters, forming transient clusters. We study the phase segregation of such passive advective scalars in a medium of dynamic asters, as a function of the aster density and the ratio of the rates of aster remodeling to particle diffusion. The dynamics of coarsening shows a violation of Porod behavior; the growing domains have diffuse interfaces and low interfacial tension. The phase-segregated steady state shows strong macroscopic fluctuations characterized by multiscaling and intermittency, signifying rapid reorganization of macroscopic structures. We expect these unique nonequilibrium features to manifest in the actin-dependent molecular clustering at the cell surface.

}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.116.068306}, author = {Das, Amit and Polley, Anirban and Rao, Madan} } @article {11603, title = {Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016 Nov 16}, abstract = {

During illumination, the light-sensitive plasma membrane (rhabdomere) of Drosophila photoreceptors undergoes turnover with consequent changes in size and composition. However, the mechanism by which illumination is coupled to rhabdomere turnover remains unclear. We find that photoreceptors contain a light-dependent phospholipase D (PLD) activity. During illumination, loss of PLD resulted in an enhanced reduction in rhabdomere size, accumulation of Rab7 positive, rhodopsin1-containing vesicles (RLVs) in the cell body and reduced rhodopsin protein. These phenotypes were associated with reduced levels of phosphatidic acid, the product of PLD activity and were rescued by reconstitution with catalytically active PLD. In wild-type photoreceptors, during illumination, enhanced PLD activity was sufficient to clear RLVs from the cell body by a process dependent on Arf1-GTP levels and retromer complex function. Thus, during illumination, PLD activity couples endocytosis of RLVs with their recycling to the plasma membrane thus maintaining plasma membrane size and composition.

}, issn = {2050-084X}, doi = {10.7554/eLife.18515}, author = {Thakur, Rajan and Panda, Aniruddha and Coessens, Elise and Raj, Nikita and Yadav, Shweta and Balakrishnan, Sruthi and Zhang, Qifeng and Georgiev, Plamen and Basak, Bishal and Pasricha, Renu and Wakelam, Michael Jo and Ktistakis, Nicholas T and Raghu, Padinjat} } @article {5302, title = {PIMA: Protein-Protein interactions in Macromolecular Assembly - a web server for its Analysis and Visualization.}, journal = {Bioinformation}, volume = {12}, year = {2016}, month = {2016}, pages = {9-11}, abstract = {

Protein-protein interactions are essential for the basic biological machinery of the cell. This is important for processes like protein synthesis, enzyme kinetics, molecular assembly and signal transduction. A high number of macromolecular structural complexes are known due to recent advances in structure determination techniques. Therefore, it is of interest to develop an interactive tool to objectively analyze large protein complexes. Hence, we describe the development and utility of a web enabled application named {\textquoteright}Protein-Protein Interaction in Macro-molecular Assembly{\textquoteright} (PIMA) for the analysis of large protein assemblies. The intricate details of physical interactions amongst protein subunits in a large complex are presented as simple user preferred interactive network diagrams.

}, issn = {0973-2063}, doi = {10.6026/97320630012009}, author = {Kaleeckal Mathew, Oommen and Sowdhamini, Ramanathan} } @article {7043, title = {PIMADb: A Database of Protein-Protein Interactions in Huge Macromolecular Assemblies.}, journal = {Bioinform Biol Insights}, volume = {10}, year = {2016}, month = {2016}, pages = {105-9}, abstract = {

Protein-protein interactions play a very important role in the process of cellular functionality. Intricate details about the interactions between the proteins in a macromolecular assembly are important to understand the function and significance of protein complexes. We are reporting about a database of protein-protein interactions in huge macromolecular assemblies (PIMADb) that records the intrinsic details of 189,532 interchain interactions in 40,049 complexes from the Protein Data Bank. These details include the results of the quantification and analysis of all the interactions in the complex. The availability of interprotomer interaction networks can enable the design of point mutation experiments. PIMADb can be accessed from the URL: http://caps.ncbs.res.in/pimadb.

}, issn = {1177-9322}, doi = {10.4137/BBI.S38416}, author = {Mathew, Oommen K and Sowdhamini, Ramanathan} } @article {3559, title = {Plasticity in Repressor-DNA Interactions Neutralizes Loss of Symmetry in Bipartite Operators.}, journal = {J Biol Chem}, volume = {291}, year = {2016}, month = {2016 Jan 15}, pages = {1235-42}, abstract = {

Transcription factor-DNA interactions are central to gene regulation. Many transcription factors regulate multiple target genes and can bind sequences that do not conform strictly to the consensus. To understand the structural mechanism utilized by the transcription regulators to bind diverse target sequences, we have employed the repressor AraR from Bacillus subtilis as a model system. AraR is known to bind to eight different operator sites in the bacterial genome. Although there are differences in the sequences of four of these operators, ORE1, ORX1, ORA1, and ORR3, the AraR-DNA binding domain (AraR-DBD) as well as full-length AraR unexpectedly binds to each of these sequences with similar affinities as measured by fluorescence anisotropy experiments. We have determined crystal structures of AraR-DBD in complex with two different natural operators ORE1 and ORX1 up to 2.07 and 1.97 {\r A} resolution, respectively. These structures were compared with the previously reported structures of AraR-DBD bound to two other natural operators (ORA1 and ORR3). Interactions of two molecules of AraR-DBD with the symmetric operator, ORE1, are identical, but their interaction with the non-symmetric operator ORX1 results in breakdown of the symmetry in protein-DNA interactions. The novel interactions observed are accompanied by local conformational change in the DNA. ChIP-sequencing (ChIP-Seq) data on other transcription factors has shown that they can bind to diverse targets, and hence the plasticity exhibited by AraR may be a general phenomenon. The ability of transcription factors to form alternate interactions may be important for employment in new functions and evolution of novel regulatory circuits.

}, issn = {1083-351X}, doi = {10.1074/jbc.M115.689695}, author = {Jain, Deepti and Narayanan, Naveen and Nair, Deepak T} } @article {8357, title = {Protein Domain-Swapping Can Be a Consequence of Functional Residues.}, journal = {J Phys Chem B}, volume = {120}, year = {2016}, month = {2016 Jul 21}, pages = {6929-38}, abstract = {

Monomer topology has been implicated in domain-swapping, a potential first step on the route to disease-causing protein aggregation. Despite having the same topology (β1-α1-β2-β3-β4-β5), the cysteine protease inhibitor stefin-B domain swaps more readily than a single-chain variant of the heterodimeric sweet protein monellin (scMn). Here, we computationally study the folding of stefin-B and scMn in order to understand the molecular basis for the difference in their domain-swapping propensities. In agreement with experiments, our structure-based simulations show that scMn folds cooperatively without the population of an intermediate while stefin-B populates an equilibrium intermediate state. Since the simulation intermediate has only one domain structured (β3-β4-β5), it can directly lead to domain-swapping. Using computational variants of stefin-B, we show that the population of this intermediate is caused by regions of stefin-B that have been implicated in protease inhibition. We also find that the protease-binding regions are located on two structural elements and localized in space. In contrast, the residues that contribute to the sweetness of monellin are not localized to a few structural elements but are distributed over the protein fold. We conclude that the distributed functional residues of monellin do not induce large local perturbations in the protein structure, eliminating the formation of folding intermediates and in turn domain-swapping. On the other hand, the localized protease-binding regions of stefin-B promote the formation of a folding intermediate which can lead to domain-swapping. Thus, domain-swapping can be a direct consequence of the constraints that function imposes on the protein structure.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.6b03968}, author = {Mascarenhas, Nahren Manuel and Gosavi, Shachi} } @article {5311, title = {Protein sequence design and its applications.}, journal = {Curr Opin Struct Biol}, volume = {37}, year = {2016}, month = {2016 Apr}, pages = {71-80}, abstract = {

Design of proteins has far-reaching potentials in diverse areas that span repurposing of the protein scaffold for reactions and substrates that they were not naturally meant for, to catching a glimpse of the ephemeral proteins that nature might have sampled during evolution. These non-natural proteins, either in synthesized or virtual form have opened the scope for the design of entities that not only rival their natural counterparts but also offer a chance to visualize the protein space continuum that might help to relate proteins and understand their associations. Here, we review the recent advances in protein engineering and design, in multiple areas, with a view to drawing attention to their future potential.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2015.12.004}, author = {Sandhya, Sankaran and Mudgal, Richa and Kumar, Gayatri and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} } @article {7080, title = {Quantum dot-loaded monofunctionalized DNA icosahedra for single-particle tracking of endocytic pathways.}, journal = {Nat Nanotechnol}, year = {2016}, month = {2016 Aug 22}, abstract = {

Functionalization of quantum dots (QDs) with a single biomolecular tag using traditional approaches in bulk solution has met with limited success. DNA polyhedra consist of an internal void bounded by a well-defined three-dimensional structured surface. The void can house cargo and the surface can be functionalized with stoichiometric and spatial precision. Here, we show that monofunctionalized QDs can be realized by encapsulating QDs inside DNA icosahedra and functionalizing the DNA shell with an endocytic ligand. We deployed the DNA-encapsulated QDs for real-time imaging of three different endocytic ligands-folic acid, galectin-3 (Gal3) and the Shiga toxin B-subunit (STxB). Single-particle tracking of Gal3- or STxB-functionalized QD-loaded DNA icosahedra allows us to monitor compartmental dynamics along endocytic pathways. These DNA-encapsulated QDs, which bear a unique stoichiometry of endocytic ligands, represent a new class of molecular probes for quantitative imaging of endocytic receptor dynamics.

}, issn = {1748-3395}, doi = {10.1038/nnano.2016.150}, author = {Bhatia, Dhiraj and Arumugam, Senthil and Nasilowski, Michel and Joshi, Himanshu and Wunder, Christian and Chambon, Val{\'e}rie and Prakash, Ved and Grazon, Chlo{\'e} and Nadal, Brice and Maiti, Prabal K and Johannes, Ludger and Dubertret, Benoit and Krishnan, Yamuna} } @article {807, title = {Rapid and enhanced remote homology detection by cascading hidden Markov model searches in sequence space.}, journal = {Bioinformatics}, volume = {32}, year = {2016}, month = {2015 Oct 10}, pages = {338-44}, chapter = {338}, abstract = {

MOTIVATION: In the post-genomic era, automatic annotation of protein sequences using computational homology-based methods is highly desirable. However, often protein sequences diverge to an extent where detection of homology and automatic annotation transfer is not straightforward. Sophisticated approaches to detect such distant relationships are needed. We propose a new approach to identify deep evolutionary relationships of proteins to overcome shortcomings of the available methods.

RESULTS: We have developed a method to identify remote homologues more effectively from any protein sequence database by using several cascading events with Hidden Markov Models (C-HMM). We have implemented clustering of hits and profile generation of hit clusters to effectively reduce the computational timings of the cascaded sequence searches. Our C-HMM approach could cover 94, 83 and 40\% coverage at family, superfamily and fold levels, respectively, when applied on diverse protein folds. We have compared C-HMM with various remote homology detection methods and discuss the trade-offs between coverage and false positives.

AVAILABILITY AND IMPLEMENTATION: A standalone package implemented in Java along with a detailed documentation can be downloaded from https://github.com/RSLabNCBS/C-HMMSupplementary information: Supplementary data are available at Bioinformatics online.

CONTACT: mini@ncbs.res.in.

}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btv538}, author = {Kaushik, Swati and Nair, Anu G and Mutt, Eshita and Subramanian, Hari Prasanna and Sowdhamini, Ramanathan} } @article {3575, title = {Rational design of a quantitative, pH-insensitive, nucleic acid based fluorescent chloride reporter}, journal = {Chemical Science }, volume = {7}, year = {2016}, pages = {1946-1953}, abstract = {

Chloride plays a major role in cellular homeostasis by regulating the lumenal pH of intracellular organelles. We have described a pH-independent, fluorescent chloride reporter called Clensor that has successfully measured resting chloride in organelles of living cells. Here, we describe the rational design of Clensor. Clensor integrates a chloride sensitive fluorophore called 10,10'-bis[3-carboxypropyl]-9,9'-biacridinium dinitrate (BAC) with the programmability, modularity and targetability available to nucleic acid scaffolds. We show that simple conjugation of BAC to a DNA backbone fails to yield a viable chloride-sensitive reporter. Fluorescence intensity and lifetime investigations on a series of BAC-functionalized structural variants yielded molecular insights that guided the rational design and successful realization of the chloride sensitive fluorescent reporter, Clensor. This study provides some general design principles that would aid the realization of diverse ion-sensitive nucleic acid reporters based on the sensing strategy of Clensor.

}, doi = {10.1039/C5SC04002G }, author = {Prakash, Ved and Saha, Sonali and Chakraborty, Kasturi and Krishnan, Yamuna} } @article {3541, title = {Rational elicitation of cold-sensitive phenotypes.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 May 3}, pages = {E2506-15}, abstract = {

Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes.

}, issn = {1091-6490}, doi = {10.1073/pnas.1604190113}, author = {Baliga, Chetana and Majhi, Sandipan and Mondal, Kajari and Bhattacharjee, Antara and VijayRaghavan, K and Varadarajan, Raghavan} } @article {3572, title = {Reactive Oxygen Species Play an Important Role in the Bactericidal Activity of Quinolone Antibiotics.}, journal = {Angew Chem Int Ed Engl}, volume = {55}, year = {2016}, month = {2016 Feb}, pages = {2397-400}, abstract = {

Recent studies posit that reactive oxygen species (ROS) contribute to the cell lethality of bactericidal antibiotics. However, this conjecture has been challenged and remains controversial. To resolve this controversy, we adopted a strategy that involves DNA polymerase IV (PolIV). The nucleotide pool of the cell gets oxidized by ROS and PolIV incorporates the damaged nucleotides (especially 8oxodGTP) into the genome, which results in death of the bacteria. By using a combination of structural and biochemical tools coupled with growth assays, it was shown that selective perturbation of the 8oxodGTP incorporation activity of PolIV results in considerable enhancement of the survival of bacteria in the presence of the norfloxacin antibiotic. Our studies therefore indicate that ROS induced in bacteria by the presence of antibiotics in the environment contribute significantly to cell lethality.

}, issn = {1521-3773}, doi = {10.1002/anie.201509340}, author = {Kottur, Jithesh and Nair, Deepak T} } @article {11629, title = {A reassessment of Melanophidium G{\"u}nther, 1864 (Squamata: Serpentes:
Uropeltidae) from the Western Ghats of peninsular India, with the description of a new species.}, journal = {Zootaxa}, volume = {4085}, year = {2016}, month = {2016 Mar 04}, pages = {481-503}, abstract = {

A new species of the uropeltid snake genus, Melanophidium G{\"u}nther, 1864 is described based on a series of eight specimens. Melanophidium khairei sp. nov. is the fourth species described in the genus, and the first for 144 years. Superficially M. khairei sp. nov. resembles M. punctatum Beddome, 1871 in being piebald and punctate (and it was previously misidentified as M. punctatum), but in many scalation characters it more closely resembles M. wynaudense (Beddome, 1863). The new species occurs in southern Maharashtra, Goa, and northern Karnataka, in the Western Ghats region of peninsula India. It is the most northerly member of its genus. Lectotypes and paralectotypes are designated for M. wynaudense, M. bilineatum Beddome, 1870, and M. punctatum. A new key to the species of Melanophidium is presented. Aspects of the morphology, taxonomy and distribution of the three previously described species of Melanophidium are reviewed and revised.

}, issn = {1175-5334}, doi = {10.11646/zootaxa.4085.4.2}, author = {Gower, David J and Giri, Varad and Captain, Ashok and Wilkinson, Mark} } @article {16571, title = {Re-discovery of Calinaga aborica Tytler, 1915 (Lepidoptera: Nymphalidae: Calinaginae) from Arunachal Pradesh, India}, journal = {Journal of Threatened Taxa}, volume = {8}, year = {2016}, month = {2016}, pages = {8618{\textendash}8622}, author = {Sondhi, S. and Karmakar, T. and Sondhi, Y. and Jhaveri, R. and Kunte, Krushnamegh} } @article {11585, title = {Regulation of Store-Operated Ca(2+) Entry by Septins.}, journal = {Front Cell Dev Biol}, volume = {4}, year = {2016}, month = {2016}, pages = {142}, abstract = {

The mechanism of store-operated Ca(2+) entry (SOCE) brings extracellular Ca(2+) into cells after depletion of intracellular Ca(2+) stores. Regulation of Ca(2+) homeostasis by SOCE helps control various intracellular signaling functions in both non-excitable and excitable cells. Whereas essential components of the SOCE pathway are well characterized, molecular mechanisms underlying regulation of this pathway need investigation. A class of proteins recently demonstrated as regulating SOCE is septins. These are filament-forming GTPases that assemble into higher order structures. One of their most studied cellular functions is as a molecular scaffold that creates diffusion barriers in membranes for a variety of cellular processes. Septins regulate SOCE in mammalian non-excitable cells and in Drosophila neurons. However, the molecular mechanism of SOCE-regulation by septins and the contribution of different subgroups of septins to SOCE-regulation remain to be understood. The regulation of SOCE is relevant in multiple cellular contexts as well as in diseases, such as the Severe Combined Immunodeficiency (SCID) syndrome and neurodegenerative syndromes like Alzheimer{\textquoteright}s, Spino-Cerebellar Ataxias and Parkinson{\textquoteright}s. Moreover, Drosophila neurons, where loss of SOCE leads to flight deficits, are a possible cellular template for understanding the molecular basis of neuronal deficits associated with loss of either the Inositol-1,4,5-trisphosphate receptor (IP3R1), a key activator of neuronal SOCE or the Endoplasmic reticulum resident Ca(2+) sensor STIM1 (Stromal Interaction Molecule) in mouse. This perspective summarizes our current understanding of septins as regulators of SOCE and discusses the implications for mammalian neuronal function.

}, doi = {10.3389/fcell.2016.00142}, author = {Deb, Bipan K and Hasan, Gaiti} } @article {11658, title = {Regulation of VDAC trafficking modulates cell death.}, journal = {Cell Death Discov}, volume = {2}, year = {2016}, month = {2016}, pages = {16085}, abstract = {

The voltage-dependent anion channel (VDAC) and mitochondria-associated hexokinase (HxK) have crucial roles in both cell survival and death. Both the individual abundances and their ratio seem to influence the balance of survival and death and are thus critical in scenarios, such as neurodegeneration and cancer. Elevated levels of both VDAC and HxK have been reported in cancerous cells. Physical interaction is surmised and specific residues or regions involved have been identified, but details of the interaction and the mechanism by which it modulates survival are yet to be elucidated. We and others have shown that heterologous expression of VDAC can induce cell death, which can be mitigated by concomitant overexpression of HxK. We have also observed that upon overexpression, fluorescently tagged VDAC is distributed between the cytosol and mitochondria. In this study, we show that cell death ensues only when the protein, which is synthesized on cytoplasmic ribosomes, migrates to the mitochondrion. Further, coexpression of rat HxK II (rHxKII) can delay the translocation of human VDAC1 (hVDAC1) protein to mitochondria and thereby inhibit VDAC-induced cell death. Variation in the level of HxK protein as seen endogenously in different cell lines, or as experimentally manipulated by silencing and overexpression, can lead to differential VDAC translocation kinetics and related cell death. The N-terminal region of HxK and the Glu73 residue of hVDAC1, which have previously been implicated in a physical interaction, are required for cytosolic retention of VDAC. Finally, we show that, in otherwise unperturbed cells in culture, there is a small but significant amount of soluble VDAC in the cytosol present in a complex with HxK. This complex could well determine how a cell is poised with respect to incoming thanatopic signals, thereby tilting the survival/death balance in pharmacologically interesting situations, such as neurodegeneration and cancer.

}, doi = {10.1038/cddiscovery.2016.85}, author = {Dubey, Ashvini K and Godbole, Ashwini and Mathew, M K} } @article {7679, title = {Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins.}, journal = {Evol Bioinform Online}, volume = {12}, year = {2016}, month = {2016}, pages = {201-11}, abstract = {

Myosins are actin-based motor proteins involved in many cellular movements. It is interesting to study the evolutionary patterns and the functional attributes of various types of myosins. Computational search algorithms were performed to identify putative myosin members by phylogenetic analysis, sequence motifs, and coexisting domains. This study is aimed at understanding the distribution and the likely biological functions of myosins encoded in various taxa and available eukaryotic genomes. We report here a phylogenetic analysis of around 4,064 myosin motor domains, built entirely from complete or near-complete myosin repertoires incorporating many unclassified, uncharacterized sequences and new myosin classes, with emphasis on myosins from Fungi, Haptophyta, and other Stramenopiles, Alveolates, and Rhizaria (SAR). The identification of large classes of myosins in Oomycetes, Cellular slime molds, Choanoflagellates, Pelagophytes, Eustigmatophyceae, Fonticula, Eucoccidiorida, and Apicomplexans with novel myosin motif variants that are conserved and thus presumably functional extends our knowledge of this important family of motor proteins. This work provides insights into the distribution and probable function of myosins including newly identified myosin classes.

}, issn = {1176-9343}, doi = {10.4137/EBO.S39880}, author = {Pasha, Shaik Naseer and Meenakshi, Iyer and Sowdhamini, Ramanathan} } @article {8349, title = {{\textquoteright}On the rocks{\textquoteright}: reproductive biology of the endemic toad Xanthophryne (Anura: Bufonidae) from the Western Ghats, India }, journal = {Journal of Natural History}, volume = {50}, year = {2016}, month = {07/2016}, pages = {2557-2572}, chapter = {2557}, abstract = {

Xanthophryne is a toad genus endemic to the northern Western Ghats of India, with two extant sister species\ {\textendash}\ Xanthophryne koynayensis and Xanthophryne tigerina. Both species are local endemics and endangered. We studied reproductive biology of these toads and found that they are specialized to the lateritic rocky outcrops at mid-elevations in high rainfall areas. Xanthophryne toads have sporadic, multiple spawning bouts lasting 2{\textendash}4\ days during early monsoon. In this explosive breeding behaviour, we observed male toads to engage in {\textquoteleft}pelvic thrusts{\textquoteright}, a unique and novel behaviour among anurans. Females oviposit in shallow pools in depressions of lateritic boulders where their tadpoles metamorphose. These ephemeral rocky pools have limited resources and they desiccate rapidly with a break in the rains. To mitigate the stochastic risk of desiccation and subsequent large-scale egg/tadpole mortality, females may disperse their reproductive investment spatially and temporally in multiple clutches, and tadpoles metamorphose rapidly. Here, we describe the amplexus, spawning and male advertisement call, and provide a comparative account of the life history traits of the two Xanthophryne species. These toads face numerous threats and are in need of urgent conservation action. These toads, seemingly well adapted to the isolated rocky outcrops, offer an excellent opportunity to understand endemism, mating systems, anuran ecology and behaviour.

}, doi = {10.1080/00222933.2016.1200686}, author = {Gaitonde, Nikhil and Giri, Varad B and Kunte, Krushnamegh} } @article {7592, title = {Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration.}, journal = {PLoS Comput Biol}, volume = {12}, year = {2016}, month = {2016 Sep}, pages = {e1005080}, abstract = {

In reward learning, the integration of NMDA-dependent calcium and dopamine by striatal projection neurons leads to potentiation of corticostriatal synapses through CaMKII/PP1 signaling. In order to elicit the CaMKII/PP1-dependent response, the calcium and dopamine inputs should arrive in temporal proximity and must follow a specific (dopamine after calcium) order. However, little is known about the cellular mechanism which enforces these temporal constraints on the signal integration. In this computational study, we propose that these temporal requirements emerge as a result of the coordinated signaling via two striatal phosphoproteins, DARPP-32 and ARPP-21. Specifically, DARPP-32-mediated signaling could implement an input-interval dependent gating function, via transient PP1 inhibition, thus enforcing the requirement for temporal proximity. Furthermore, ARPP-21 signaling could impose the additional input-order requirement of calcium and dopamine, due to its Ca2+/calmodulin sequestering property when dopamine arrives first. This highlights the possible role of phosphoproteins in the temporal aspects of striatal signal transduction.

}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1005080}, author = {Nair, Anu G and Bhalla, Upinder S and Hellgren Kotaleski, Jeanette} } @article {8352, title = {The role of wet-zone fragmentation in shaping biodiversity patterns in peninsular India: insights from the caecilian amphibian Gegeneophis }, journal = {JOURNAL OF BIOGEOGRAPHY }, volume = {43}, year = {2016}, month = {06/2016}, pages = {1091-1102 }, abstract = {

Aim Indian biodiversity is concentrated in the wet zone, which is disjunctly distributed in the north-east and in the peninsular Western and Eastern Ghats. The Eastern Ghats region is smaller and less well explored biologically and the affinities and origins of its biota poorly understood. Our aim was to assess whether divergence between east and west lineages might have been caused by fragmentation of the wet zone during Pleistocene climatic fluctuations, by Late Miocene wet-zone contraction or by more ancient events. We present the first dated phylogenetic test of these alternatives by inferring relationships and dating divergences within a wet-zone-restricted lineage endemic to the Eastern and Western Ghats.

}, doi = {10.1111/jbi.12710 }, author = {Gower, David J. and Agarwal, Ishan and Karanth, K. Praveen and Datta-Roy, Aniruddha and Giri, Varad B and Wilkinson, Mark and San Mauro, Diego} } @article {8756, title = {RStrucFam: a web server to associate structure and cognate RNA for RNA-binding proteins from sequence information.}, journal = {BMC Bioinformatics}, volume = {17}, year = {2016}, month = {2016 Oct 7}, pages = {411}, abstract = {

BACKGROUND: RNA-binding proteins (RBPs) interact with their cognate RNA(s) to form large biomolecular assemblies. They are versatile in their functionality and are involved in a myriad of processes inside the cell. RBPs with similar structural features and common biological functions are grouped together into families and superfamilies. It will be useful to obtain an early understanding and association of RNA-binding property of sequences of gene products. Here, we report a web server, RStrucFam, to predict the structure, type of cognate RNA(s) and function(s) of proteins, where possible, from mere sequence information.

RESULTS: The web server employs Hidden Markov Model scan (hmmscan) to enable association to a back-end database of structural and sequence families. The database (HMMRBP) comprises of 437 HMMs of RBP families of known structure that have been generated using structure-based sequence alignments and 746 sequence-centric RBP family HMMs. The input protein sequence is associated with structural or sequence domain families, if structure or sequence signatures exist. In case of association of the protein with a family of known structures, output features like, multiple structure-based sequence alignment (MSSA) of the query with all others members of that family is provided. Further, cognate RNA partner(s) for that protein, Gene Ontology (GO) annotations, if any and a homology model of the protein can be obtained. The users can also browse through the database for details pertaining to each family, protein or RNA and their related information based on keyword search or RNA motif search.

CONCLUSIONS: RStrucFam is a web server that exploits structurally conserved features of RBPs, derived from known family members and imprinted in mathematical profiles, to predict putative RBPs from sequence information. Proteins that fail to associate with such structure-centric families are further queried against the sequence-centric RBP family HMMs in the HMMRBP database. Further, all other essential information pertaining to an RBP, like overall function annotations, are provided. The web server can be accessed at the following link: http://caps.ncbs.res.in/rstrucfam .

}, issn = {1471-2105}, doi = {10.1186/s12859-016-1289-x}, author = {Ghosh, Pritha and Mathew, Oommen K and Sowdhamini, Ramanathan} } @article {7041, title = {Savannahs of Asia: antiquity, biogeography, and an uncertain future.}, journal = {Philos Trans R Soc Lond B Biol Sci}, volume = {371}, year = {2016}, month = {2016 Sep 19}, abstract = {

The savannahs of Asia remain locally unrecognized as distinctive ecosystems, and continue to be viewed as degraded forests or seasonally dry tropical forests. These colonial-era legacies are problematic, because they fail to recognize the unique diversity of Asian savannahs and the critical roles of fire and herbivory in maintaining ecosystem health and diversity. In this review, we show that: the palaeo-historical evidence suggests that the savannahs of Asia have existed for at least 1 million years, long before widespread landscape modification by humans; savannah regions across Asia have levels of C4 grass endemism and diversity that are consistent with area-based expectations for non-Asian savannahs; there are at least three distinct Asian savannah communities, namely deciduous broadleaf savannahs, deciduous fine-leafed and spiny savannahs and evergreen pine savannahs, with distinct functional ecologies consistent with fire- and herbivory-driven community assembly. Via an analysis of savannah climate domains on other continents, we map the potential extent of savannahs across Asia. We find that the climates of African savannahs provide the closest analogues for those of Asian deciduous savannahs, but that Asian pine savannahs occur in climates different to any of the savannahs in the southern continents. Finally, we review major threats to the persistence of savannahs in Asia, including the mismanagement of fire and herbivory, alien woody encroachment, afforestation policies and future climate uncertainty associated with the changing Asian monsoon. Research agendas that target these issues are urgently needed to manage and conserve these ecosystems.This article is part of the themed issue {\textquoteright}Tropical grassy biomes: linking ecology, human use and conservation{\textquoteright}.

}, issn = {1471-2970}, doi = {10.1098/rstb.2015.0305}, author = {Ratnam, Jayashree and Tomlinson, Kyle W and Rasquinha, Dina N and Sankaran, Mahesh} } @article {5241, title = {Secondary Structural Change Can Occur Diffusely and Not Modularly during Protein Folding and Unfolding Reactions.}, journal = {J Am Chem Soc}, volume = {138}, year = {2016}, month = {2016 May 11}, pages = {5866-78}, abstract = {

A major goal of protein folding studies is to understand the structural basis of the coupling between stabilizing interactions, which leads to cooperative conformational change. The goal is challenging because of the difficulty in simultaneously measuring global cooperativity by determining population distributions of the conformations present, and the structures of these conformations. Here, hydrogen exchange (HX) into the small protein monellin was carried out under conditions where structure-opening is rate limiting for most backbone amide sites. Detection by mass spectrometry allowed characterization of not only segment-specific structure-opening rates but also the cooperativity of unfolding of the different secondary structural segments of the protein. The segment-specific pattern of HX reveals that the backbone hydrogen-bonding network disassembles in a structurally diffuse, asynchronous manner. A comparison of the site-specific transient opening rates of secondary and tertiary structure in the protein provides a structural rationale for the observation that unfolding is hierarchical and describable by exponential kinetics, despite being diffuse. Since unfolding was studied in native conditions, the sequence of events during folding in the same conditions will be the reverse of the sequence of events observed during unfolding. Hence, the formation of secondary structural units during folding would also occur in a non-cooperative, diffuse, and asynchronous manner.

}, issn = {1520-5126}, doi = {10.1021/jacs.6b03356}, author = {Malhotra, Pooja and Udgaonkar, Jayant B} } @article {5217, title = {Seed size predicts community composition and carbon storage potential of tree communities in rainforest fragments in India{\textquoteright}s Western Ghats}, journal = {Journal of Applied Ecology }, volume = {53}, year = {2016}, month = {03/2016}, pages = {837-845}, doi = {10.1111/1365-2664.12626}, author = {Osuri, A. M and Sankaran, M.} } @article {4891, title = {Selection Maintains Apparently Degenerate Metabolic Pathways due to Tradeoffs in Using Methylamine for Carbon versus Nitrogen.}, journal = {Curr Biol}, volume = {26}, year = {2016}, month = {2016 Jun 6}, pages = {1416-26}, abstract = {

Microorganisms often encode multiple non-orthologous metabolic modules that catalyze the same reaction. However, little experimental evidence actually demonstrates a selective basis for metabolic degeneracy. Many methylotrophs-microorganisms that grow on reduced single-carbon compounds-like Methylobacterium extorquens AM1 encode two routes for methylamine oxidation: the periplasmic methylamine dehydrogenase (MaDH) and the cytoplasmic N-methylglutamate (NMG) pathway. In Methylobacterium extorquens AM1, MaDH is essential for methylamine growth, but the NMG pathway has no known physiological role. Here, we use experimental evolution of two isolates lacking (or incapable of using) MaDH to uncover the physiological challenges that need to be overcome in order to use the NMG pathway for growth on methylamine as a carbon and energy source. Physiological characterization of the evolved isolates revealed regulatory rewiring to increase expression of the NMG pathway and novel mechanisms to mitigate cytoplasmic ammonia buildup. These adaptations led us to infer and validate environmental conditions under which the NMG pathway is advantageous compared to MaDH. The highly expressed MaDH enables rapid growth on high concentrations of methylamine as the primary carbon and energy substrate, whereas the energetically expensive NMG pathway plays a pivotal role during growth with methylamine as the sole nitrogen source, which we demonstrate is especially true under limiting concentrations (\<1\ mM). Tradeoffs between cellular localization and ammonium toxicity lead to selection for this apparent degeneracy as it is beneficial to facultative methylotrophs that have to switch between using methylamine as a carbon and energy source or just a nitrogen source.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2016.04.029}, author = {Nayak, Dipti D and Agashe, Deepa and Lee, Ming-Chun and Marx, Christopher J} } @article {11586, title = {Sensory specificity and speciation: a potential neuronal pathway for host fruit odour discrimination in Rhagoletis pomonella.}, journal = {Proc Biol Sci}, volume = {283}, year = {2016}, month = {2016 Dec 28}, abstract = {

Behavioural changes in habitat or mate choice can trigger population divergence, leading to speciation. However, little is known about the neurological bases for such changes. Rhagoletis pomonella (Diptera: Tephritidae) is a model for ecological speciation via host plant shifts. Within the past 180 years, Rhagoletis flies infesting hawthorn (Crataegus spp.) shifted to attack domesticated apple (Malus pumila). The two populations differ in their olfactory preferences for apple versus hawthorn fruit. Here, we looked for patterns of sensory organization that may have contributed to this shift by characterizing the morphology, specificity and distribution of olfactory sensory neurons (OSNs) on the antennae of Rhagoletis responding to host fruit and non-host volatiles. Of 28 OSN classes identified, two colocalized OSN pairs were found that specifically responded to the major behavioural attractant and antagonist volatiles for each fly population. A reversal in the response of these OSNs to fruit volatiles, either through a switch in receptor expression between these paired neurons or changes in neuronal projections in the brain, could therefore account for the behavioural difference between apple and hawthorn flies. The finding supports the hypothesis that relatively minor changes in olfactory sensory pathways may contribute to rapid host shifting and divergence in Rhagoletis.

}, issn = {1471-2954}, doi = {10.1098/rspb.2016.2101}, author = {Tait, Cheyenne and Batra, Srishti and Ramaswamy, Sree Subha and Feder, Jeffrey L and Olsson, Shannon B} } @article {11625, title = {sigma(2)-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila}, journal = {GENETICS}, volume = {1}, year = {2016}, month = {05/2016}, chapter = {369}, abstract = {

The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to sigma(2)-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the sigma(2)-adaptin mutation. Genetic perturbation of sigma(2)-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38 degrees. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor beta (TGF beta) signaling was altered in these mutants and was restored by normalizing sigma(2)-adaptin in neurons. Thus, our data suggest that (1) while sigma(2)-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) sigma(2)-adaptin regulates NMJ morphology by attenuating TGF beta signaling.

}, doi = {10.1534/genetics.115.183863}, author = {Choudhury, Saumitra Dey and Mushtaq, Zeeshan and Reddy-Alla, Suneel and Balakrishnan, Sruthi S and Thakur, Rajan S and Krishnan, Kozhalmannom S. and Raghu, Padinjat and Ramaswami, Mani and Kumar, Vimlesh} } @article {3564, title = {Silver based nanomaterial, as a selective colorimetric sensor for visual detection of post harvest spoilage in onion}, journal = {Sensors and Actuators B: Chemical}, volume = {228}, year = {2016}, month = {June 2016}, pages = {471{\textendash}479}, abstract = {

Onion being a semi-perishable horticultural bulb crop gets subjected to deterioration during the storage, which ultimately leads to huge monetary losses every year. Specific detection tools for onion spoilage will be an asset in relieving losses during post-harvest storage. In this context silver based yellow colored colloidal nanoparticle (AgY-NPs) solution was synthesized and evaluated as a visual sensor for the organo-sulfur compound released during the spoilage of onions. The visual changes during the spoilage was monitored for ten days wherein the yellow color of the AgY colloidal solution changed to orange, pink and finally turned transparent. Simultaneous analysis carried out by UV{\textendash}Vis spectroscopy and colorimeteric analysis corroborates our investigation of AgY-NPs as a visual sensor displaying selectivity and specificity for volatile sulphur compound responsible for spoilage of onions. Furthermore, analysis of AgY-NPs in presence of healthy onions showed distinct visual results which were complemented by probable mechanism. Besides this the structural changes in AgY-NPs due to incorporation of sulphur compounds were supported by Powder X-ray diffraction (PXRD), Raman Analysis, Fourier Transform-Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) which clearly indicated the capacity of these AgY-NPs as a powerful detection tool for onion spoilage.

}, doi = {doi:10.1016/j.snb.2016.01.049}, url = {http://www.sciencedirect.com/science/article/pii/S0925400516300478}, author = {Sachdev, Divya. and Kumar, Vinay. and Maheshwari, Priyanka H. and Pesricha, Renu} } @article {3557, title = {A simple non-invasive technique for venom milking from a solitary wasp Delta conoideum Gmelin (Hymenoptera: Vespidae).}, journal = {Toxicon}, volume = {109}, year = {2016}, month = {2016 Jan}, pages = {4-6}, abstract = {

Prospecting wasp, ant and bee venom for active bio-molecules has gained considerable interest among researchers in recent years. Collecting sufficient quantity of venom from solitary wasps without sacrificing them is often difficult. Here we describe a non-invasive technique for collecting venom from a solitary wasp Delta conoideum Gmelin (Red-backed potter wasp). Venom was milked by presenting an agar block to a single female wasp for stinging. The venom was extracted from the agar block using ACN: water solvent system. The total protein in venom was estimated quantitatively and the presence of peptides in the venom was confirmed by MALDI-TOF analysis. The proposed technique is non-invasive and pure venom can be repeatedly {\textquoteright}milked{\textquoteright} using this method from other wasps and also bees without the need for sacrificing a large number of individuals.

}, issn = {1879-3150}, doi = {10.1016/j.toxicon.2015.10.023}, author = {Bhagavathula, Naga Chaitanya and Kumar, Mukesh and Krishnappa, Chandrashekra} } @article {8356, title = {Single nucleotide polymorphism in sugar pathway and disease resistance genes in sugarcane.}, journal = {Plant Cell Rep}, volume = {35}, year = {2016}, month = {2016 Aug}, pages = {1629-53}, abstract = {

KEY MESSAGE: Single nucleotide polymorphism in sugar pathway and disease resistance genes showing genetic association with sugar content and red rot resistance would be useful in marker-assisted genetic improvement of sugarcane. Validation and genotyping of potential sequence variants in candidate genes are necessary to understand their functional significance and trait association potential. We discovered, characterized, validated and genotyped SNPs and InDels in sugar pathway and disease resistance genes of Saccharum complex and sugarcane varieties using amplicon sequencing and CAPS assays. The SNPs were abundant in the non-coding 3{\textquoteright}UTRs than 5{\textquoteright}UTRs and coding sequences depicting a strong bias toward C to T transition substitutions than transversions. Sequencing of cloned amplicons validated 61.6 and 45.2\ \% SNPs detected in silico in 21 sugar pathway and 16 disease resistance genes, respectively. Sixteen SNPs in four sugar pathway genes and 10 SNPs in nine disease resistance genes were validated through cost-effective CAPS assay. Functional and adaptive significance of SNP and protein haplotypes identified in sugar pathway and disease resistance genes was assessed by correlating their allelic variation with missense amino acid substitutions in the functional domains, alteration in protein structure models and possible modulation of catalytic enzyme activity in contrasting high and low sugar and moderately red rot resistant and highly susceptible sugarcane genotypes. A strong genetic association of five SNPs in the sugar pathway and disease resistance genes, and an InDel marker in the promoter sequence of sucrose synthase-2 gene, with sugar content and red rot resistance, was evident. The functionally relevant SNPs and InDels, detected and validated in sugar pathway and disease resistance genes, and genic CAPS markers designed, would be of immense use in marker-assisted genetic improvement of sugarcane for sugar content and disease resistance.

}, issn = {1432-203X}, doi = {10.1007/s00299-016-1978-y}, author = {Parida, Swarup K and Kalia, Sanjay and Pandit, Awadhesh and Nayak, Preetam and Singh, Ram Kushal and Gaikwad, Kishor and Srivastava, Prem Shankar and Singh, Nagendra K and Mohapatra, Trilochan} } @article {7037, title = {Stacking the odds for Golgi cisternal maturation.}, journal = {Elife}, volume = {5}, year = {2016}, month = {2016 Aug 19}, abstract = {

What is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles. This motif precisely matches the cisternal maturation model of the Golgi, which was developed to explain many observed aspects of the eukaryotic secretory pathway. In our analysis cisternal maturation is a robust consequence of vesicle traffic homeostasis, independent of the underlying details of molecular interactions or spatial stacking. This architecture may have been exapted rather than selected for its role in the secretion of large cargo.

}, issn = {2050-084X}, doi = {10.7554/eLife.16231}, author = {Mani, Somya and Thattai, Mukund} } @article {3906, title = {Store-independent modulation of Ca(2+) entry through Orai by Septin 7.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, abstract = {

Orai channels are required for store-operated Ca(2+) entry (SOCE) in multiple cell types. Septins are a class of GTP-binding proteins that function as diffusion barriers in cells. Here we show that Septin 7 acts as a {\textquoteright}molecular brake{\textquoteright} on activation of Orai channels in Drosophila neurons. Lowering Septin 7 levels results in dOrai-mediated Ca(2+) entry and higher cytosolic Ca(2+) in resting neurons. This Ca(2+) entry is independent of depletion of endoplasmic reticulum Ca(2+) stores and Ca(2+) release through the inositol-1,4,5-trisphosphate receptor. Importantly, store-independent Ca(2+) entry through Orai compensates for reduced SOCE in the Drosophila flight circuit. Moreover, overexpression of Septin 7 reduces both SOCE and flight duration, supporting its role as a negative regulator of Orai channel function in vivo. Septin 7 levels in neurons can, therefore, alter neural circuit function by modulating Orai function and Ca(2+) homeostasis.

}, issn = {2041-1723}, doi = {10.1038/ncomms11751}, author = {Deb, BipanKumar and Pathak, Trayambak and Hasan, Gaiti} } @article {11635, title = {Structural and mechanistic insights into human splicing factor SF3b complex derived using an integrated approach guided by the cryo-EM density maps.}, journal = {RNA Biol}, volume = {13}, year = {2016}, month = {2016 Oct 02}, pages = {1025-1040}, abstract = {

Pre-mRNA splicing in eukaryotes is performed by the spliceosome, a highly complex macromolecular machine. SF3b is a multi-protein complex which recognizes the branch point adenosine of pre-mRNA as part of a larger U2 snRNP or U11/U12 di-snRNP in the dynamic spliceosome machinery. Although a cryo-EM map is available for human SF3b complex, the structure and relative spatial arrangement of all components in the complex are not yet known. We have recognized folds of domains in various proteins in the assembly and generated comparative models. Using an integrative approach involving structural and other experimental data, guided by the available cryo-EM density map, we deciphered a pseudo-atomic model of the closed form of SF3b which is found to be a "fuzzy complex" with highly flexible components and multiplicity of folds. Further, the model provides structural information for 5 proteins (SF3b10, SF3b155, SF3b145, SF3b130 and SF3b14b) and localization information for 4 proteins (SF3b10, SF3b145, SF3b130 and SF3b14b) in the assembly for the first time. Integration of this model with the available U11/U12 di-snRNP cryo-EM map enabled elucidation of an open form. This now provides new insights on the mechanistic features involved in the transition between closed and open forms pivoted by a hinge region in the SF3b155 protein that also harbors cancer causing mutations. Moreover, the open form guided model of the 5{\textquoteright} end of U12 snRNA, which includes the branch point duplex, shows that the architecture of SF3b acts as a scaffold for U12 snRNA: pre-mRNA branch point duplex formation with potential implications for branch point adenosine recognition fidelity.

}, issn = {1555-8584}, doi = {10.1080/15476286.2016.1218590}, author = {Rakesh, Ramachandran and Joseph, Agnel Praveen and Bhaskara, Ramachandra M and Srinivasan, Narayanaswamy} } @article {5201, title = {Structural and temporal dynamics of the bee curtain in the open-nesting honey bee species, Apis florea}, journal = {Apidologie}, year = {2016}, month = {02/2016}, abstract = {

Workers of open-nesting honey bee species form a bee curtain to cover the comb and protect it against adverse environmental conditions and predators. We studied different aspects of structural and temporal dynamics of the bee curtain in Apis florea. First, in the course of daily observations, we discovered massed flight activity (MFA) of A. florea colonies similar to that previously described for A. dorsata. The MFAs started with the opening of gaps in the curtain and appearance of chains of bees shortly before the massed take off. Second, monitoring the worker movement patterns in the outer layer indicated a constant turnover of bees in the curtain. Finally, introduction of marked 1-day-old workers showed that workers joined the curtain at a very young age. First flight activity appeared around day 20, but the majority of workers started to fly after day 47, which is twice the age at which A. mellifera workers start to forage.

}, doi = {10.1007/s13592-016-0428-8}, author = {Bhagavan, H and Muthmann, O and Brockmann, A} } @article {7590, title = {Synergism and Combinatorial Coding for Binary Odor Mixture Perception in Drosophila.}, journal = {eNeuro}, volume = {3}, year = {2016}, month = {2016 Jul-Aug}, abstract = {

Most odors in the natural environment are mixtures of several compounds. Olfactory receptors housed in the olfactory sensory neurons detect these odors and transmit the information to the brain, leading to decision-making. But whether the olfactory system detects the ingredients of a mixture separately or treats mixtures as different entities is not well understood. Using Drosophila melanogaster as a model system, we have demonstrated that fruit flies perceive binary odor mixtures in a manner that is heavily dependent on both the proportion and the degree of dilution of the components, suggesting a combinatorial coding at the peripheral level. This coding strategy appears to be receptor specific and is independent of interneuronal interactions.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0056-14.2016}, author = {Kundu, Srikanya and Ganguly, Anindya and Chakraborty, Tuhin Subhra and Kumar, Arun and Siddiqi, Obaid} } @article {8345, title = {Systematics and phylogeny of Sitana (Reptilia: Agamidae) of Peninsular India, with the description of one new genus and five new species}, journal = {Contributions to Zoology}, volume = {85}, year = {2016}, month = {2016}, pages = {67-111}, chapter = {67}, abstract = {

We revise the taxonomy of the agamid genus Sitana Cuvier, 1829, a widely distributed terrestrial lizard from the Indian subcontinent based on detailed comparative analyses of external morphology, osteology and molecular data. We sampled 81 locations spread over 160,000 km2 in Peninsular India including type localities, which represented two known and five previously undescribed species. Based on general similarity in body shape and dewlap all species were hitherto identified as members of the genus Sitana. However, Sitana deccanensis and two other morphotypes, which are endemic to north Karnataka and Maharashtra in Peninsular India, are very distinct from the rest of the known members of the genus Sitana based on their external morphology and osteology. Moreover, members of this distinct morphological group were monophyletic in the molecular tree, and this clade (clade 1) was sister to two well-supported clades (2 and 3) constituting the rest of the Sitana. The interclade genetic divergence in mtDNA between clade 1 and clades 2 and 3 was 21-23\%, whereas clade 2 and clade 3 exhibited 14-16\% genetic divergence. Thus, we designate a new genus name {\textquotedblleft}Sarada{\textquotedblright} gen. nov. for species represented in Clade 1, which also includes the recently resurrected Sitana deccanensis. We describe two new species in Sarada gen. nov. and three new species in Sitana. Similarity in the dewlap of Sitana and Sarada gen. nov. is attributed to similar function (sexual signaling) and similarity in body shape is attributed to a similar terrestrial life style and/or common ancestry.

}, author = {Deepak, V. and Giri, Varad B and Mohammad Asif and Sushil Kumar Dutta and Raju Vyas and Amod M. Zambre and Harshal Bhosale and K. Praveen Karanth} } @article {1029, title = {A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities.}, journal = {J Biomol Struct Dyn}, volume = {34}, year = {2016}, month = {2015 Nov 26}, pages = {1979-86}, chapter = {1979}, abstract = {

The Transformer2 (Tra2) proteins in humans are homologues of the Drosophila Tra2 protein. One of the two RNA-binding paralogs, Tra2β, has been very well-studied over the past decade, but not much is known about Tra2α. It was very recently shown that the two proteins demonstrate the phenomenon of paralog compensation. Here, we provide a structural basis for this genetic backup circuit, using molecular modelling and dynamics studies. We show that the two proteins display similar binding specificities, but differential affinities to a short GAA-rich RNA stretch. Starting from the 6-nucleotide RNA in the solution structure, close to 4000 virtual mutations were modelled on RNA and the domain-RNA interactions were studied after energy minimisation to convergence. Separately, another known 13-nucleotide stretch was docked and the domain-RNA interactions were observed through a 100-ns dynamics trajectory. We have also demonstrated the {\textquoteright}compensatory{\textquoteright} mechanism at the level of domains in one of the domain repeat-containing RNA-binding proteins.

}, issn = {1538-0254}, doi = {10.1080/07391102.2015.1100551}, author = {Ghosh, Pritha and Grellscheid, Sushma Nagaraja and Sowdhamini, R} } @article {11590, title = {Three-dimensional modelling of the voltage-gated sodium ion channel from Anopheles gambiae reveals spatial clustering of evolutionarily conserved acidic residues at the extracellular sites.}, journal = {Curr Neuropharmacol}, year = {2016}, month = {2016 Dec 05}, abstract = {

The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein. A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops. A model created with this arrangement shows a structure similar to low-resolution cryo-electron microscope images of a related structure. The pore entrance also shows favorable electrostatic interface. Residues responsible for the negative charge around the pore have been traced in phylogeny to highlight their importance. This model is intended for the study of pore-blocking toxins.

}, issn = {1875-6190}, author = {Vinekar, Rithvik S and Sowdhamini, Ramanathan} } @article {11593, title = {Topological organisation of the phosphatidylinositol 4,5-bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER-PM gap.}, journal = {Biochem J}, volume = {473}, year = {2016}, month = {2016 Dec 01}, pages = {4289-4310}, abstract = {

Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P2 Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid. The biochemical intermediates of this cycle and the enzymes that mediate these reactions are topologically distributed across two membrane compartments, the PM and the endoplasmic reticulum (ER). At the PM, the DG formed during PLC activation is rapidly converted into phosphatidic acid (PA) that needs to be transported to the ER where the machinery for its conversion into PI is localised. Conversely, PI from the ER needs to be rapidly transferred to the PM where it can be phosphorylated by lipid kinases to regenerate PI(4,5)P2 Thus, two lipid transport steps between membrane compartments through the cytosol are required for the replenishment of PI(4,5)P2 at the PM. Here, we review the topological constraints in the PI(4,5)P2 cycle and current understanding how these constraints are overcome during PLC signalling. In particular, we discuss the role of lipid transfer proteins in this process. Recent findings on the biochemical properties of a membrane-associated lipid transfer protein of the PITP family, PITPNM proteins (alternative name RdgBα/Nir proteins) that localise to membrane contact sites are discussed. Studies in both Drosophila and mammalian cells converge to provide a resolution to the conundrum of reciprocal transfer of PA and PI during PLC signalling.

}, issn = {1470-8728}, doi = {10.1042/BCJ20160514C}, author = {Cockcroft, Shamshad and Raghu, Padinjat} } @article {5312, title = {Transcriptional regulatory networks in Arabidopsis thaliana during single and combined stresses.}, journal = {Nucleic Acids Res}, volume = {44}, year = {2016}, month = {2016 Apr 20}, pages = {3147-64}, abstract = {

Differentially evolved responses to various stress conditions in plants are controlled by complex regulatory circuits of transcriptional activators, and repressors, such as transcription factors (TFs). To understand the general and condition-specific activities of the TFs and their regulatory relationships with the target genes (TGs), we have used a homogeneous stress gene expression dataset generated on ten natural ecotypes of the model plantArabidopsis thaliana, during five single and six combined stress conditions. Knowledge-based profiles of binding sites for 25 stress-responsive TF families (187 TFs) were generated and tested for their enrichment in the regulatory regions of the associated TGs. Condition-dependent regulatory sub-networks have shed light on the differential utilization of the underlying network topology, by stress-specific regulators and multifunctional regulators. The multifunctional regulators maintain the core stress response processes while the transient regulators confer the specificity to certain conditions. Clustering patterns of transcription factor binding sites (TFBS) have reflected the combinatorial nature of transcriptional regulation, and suggested the putative role of the homotypic clusters of TFBS towards maintaining transcriptional robustness againstcis-regulatory mutations to facilitate the preservation of stress response processes. The Gene Ontology enrichment analysis of the TGs reflected sequential regulation of stress response mechanisms in plants.

}, issn = {1362-4962}, doi = {10.1093/nar/gkv1463}, author = {Barah, Pankaj and B N, Mahantesha Naika and Jayavelu, Naresh Doni and Sowdhamini, Ramanathan and Shameer, Khader and Bones, Atle M} } @article {5297, title = {A unique mating strategy without physical contact during fertilization in Bombay Night Frogs (Nyctibatrachus humayuni) with the description of a new form of amplexus and female call.}, journal = {PeerJ}, volume = {4}, year = {2016}, month = {2016}, pages = {e2117}, abstract = {

Anurans show the highest diversity in reproductive modes of all vertebrate taxa, with a variety of associated breeding behaviours. One striking feature of anuran reproduction is amplexus. During this process, in which the male clasps the female, both individuals{\textquoteright} cloacae are juxtaposed to ensure successful external fertilization. Several types of amplexus have evolved with the diversification of anurans, and secondary loss of amplexus has been reported in a few distantly related taxa. Within Nyctibatrachus, a genus endemic to the Western Ghats of India, normal axillary amplexus, a complete loss of amplexus, and intermediate forms of amplexus have all been suggested to occur, but many species remain unstudied. Here, we describe the reproductive behaviour of N. humayuni, including a new type of amplexus. The dorsal straddle, here defined as a loose form of contact in which the male sits on the dorsum of the female prior to oviposition but without clasping her, is previously unreported for anurans. When compared to known amplexus types, it most closely resembles the form of amplexus observed in Mantellinae. Furthermore, we prove that, opposed to the situation in most anurans, male semen release happens before egg deposition. We hypothesize that the male ejaculates on the female{\textquoteright}s dorsum and that sperm subsequently runs from her back and hind legs before fertilizing the eggs. A second feature characterizing anuran breeding is the advertisement call, mostly produced solely by males. Despite recent descriptions of several new Nyctibatrachus species, few studies have explored their vocal repertoire. We describe both the male advertisement call and a female call for N. humayuni. The presence of a female call has not been reported within Nyctibatrachidae, and has been reported in less than 0.5\% of anuran species. Altogether, our results highlight a striking diversity and several unique aspects of Nyctibatrachus breeding behaviour.

}, issn = {2167-8359}, doi = {10.7717/peerj.2117}, author = {Willaert, Bert and Suyesh, Robin and Garg, Sonali and Giri, Varad B and Bee, Mark A and Biju, S D} } @article {3552, title = {Universal Poisson Statistics of mRNAs with Complex Decay Pathways.}, journal = {Biophys J}, volume = {110}, year = {2016}, month = {2016 Jan 19}, pages = {301-5}, abstract = {

Messenger RNA (mRNA) dynamics in single cells are often modeled as a memoryless birth-death process with a constant probability per unit time that an mRNA molecule is synthesized or degraded. This predicts a Poisson steady-state distribution of mRNA number, in close agreement with experiments. This is surprising, since mRNA decay is known to be a complex process. The paradox is resolved by realizing that the Poisson steady state generalizes to arbitrary mRNA lifetime distributions. A mapping between mRNA dynamics and queueing theory highlights an identifiability problem: a measured Poisson steady state is consistent with a large variety of microscopic models. Here, I provide a rigorous and intuitive explanation for the universality of the Poisson steady state. I show that the mRNA birth-death process and its complex decay variants all take the form of the familiar Poisson law of rare events, under a nonlinear rescaling of time. As a corollary, not only steady-states but also transients are Poisson distributed. Deviations from the Poisson form occur only under two conditions, promoter fluctuations leading to transcriptional bursts or nonindependent degradation of mRNA molecules. These results place severe limits on the power of single-cell experiments to probe microscopic mechanisms, and they highlight the need for single-molecule measurements.

}, issn = {1542-0086}, doi = {10.1016/j.bpj.2015.12.001}, author = {Thattai, Mukund} } @article {11602, title = {Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos.}, journal = {Sci Rep}, volume = {6}, year = {2016}, month = {2016 Nov 17}, pages = {37291}, abstract = {

Early development of certain mammalian embryos is protected by complex checkpoint systems to maintain the genomic integrity. Several metabolic pathways are modulated in response to genetic insults in mammalian cells. The present study investigated the relationship between the genetic integrity, embryo metabolites and developmental competence in preimplantation stage mouse embryos with the aim to identify early biomarkers which can predict embryonic genetic integrity using spent medium profiling by NMR spectroscopy. Embryos carrying induced DNA lesions (IDL) developed normally for the first 2.5 days, but began to exhibit a developmental delay at embryonic day 3.5(E3.5) though they were morphologically indistinguishable from control embryos. Analysis of metabolites in the spent medium on E3.5 revealed a significant association between pyruvate, lactate, glucose, proline, lysine, alanine, valine, isoleucine and thymine and the extent of genetic instability observed in the embryos on E4.5. Further analysis revealed an association of apoptosis and micronuclei frequency with P53 and Bax transcripts in IDL embryos on the E4.5 owing to delayed induction of chromosome instability. We conclude that estimation of metabolites on E3.5 in spent medium may serve as a biomarker to predict the genetic integrity in pre-implantation stage embryos which opens up new avenues to improve outcomes in clinical IVF programs.

}, issn = {2045-2322}, doi = {10.1038/srep37291}, author = {D{\textquoteright}Souza, Fiona and Pudakalakatti, Shivanand M and Uppangala, Shubhashree and Honguntikar, Sachin and Salian, Sujith Raj and Kalthur, Guruprasad and Pasricha, Renu and Appajigowda, Divya and Atreya, Hanudatta S and Adiga, Satish Kumar} } @article {3550, title = {Unraveling the Molecular Mechanism of pH-Induced Misfolding and Oligomerization of the Prion Protein.}, journal = {J Mol Biol}, volume = {428}, year = {2016}, month = {2016 Mar 27}, pages = {1345-55}, abstract = {

The misfolding of the prion protein (PrP) to aggregated forms is linked to several neurodegenerative diseases. Misfolded oligomeric forms of PrP are associated with neurotoxicity and/or infectivity, but the molecular mechanism by which they form is still poorly understood. A reduction in pH is known to be a key factor that triggers misfolded oligomer formation by PrP, but the residues whose protonation is linked with misfolding remain unidentified. The structural consequences of the protonation of these residues also remain to be determined. In the current study, amino acid residues whose protonation is critical for PrP misfolding and oligomerization have been identified using site-directed mutagenesis and misfolding/oligomerization assays. It is shown that the protonation of either H186 or D201, which mimics the effects of pathogenic mutations (H186R and D201N) at both residue sites, is critically linked to the stability, misfolding and oligomerization of PrP. Hydrogen-deuterium exchange studies coupled with mass spectrometry show that the protonation of either H186 or D201 leads to the same common structural change: increased structural dynamics in helix 1 and that in the loop between helix 1 and β-strand 2. It is shown that the protonation of either of these residues is sufficient for accelerating misfolded oligomer formation, most likely because the protonation of either residue causes the same structural perturbation. Hence, the increased structural dynamics in helix 1 and that in the loop between helix 1 and β-strand 2 appear to play an early critical role in acid-induced misfolding of PrP.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2016.01.030}, author = {Singh, Jogender and Udgaonkar, Jayant B} } @article {6135, title = {Use of evolutionary information in the fitting of atomic level protein models in low resolution cryo-EM map of a protein assembly improves the accuracy of the fitting.}, journal = {J Struct Biol}, year = {2016}, month = {2016 Jul 19}, abstract = {

Protein-protein interface residues, especially those at the core of the interface, exhibit higher conservation than residues in solvent exposed regions. Here, we explore the ability of this differential conservation to evaluate fittings of atomic models in low-resolution cryo-EM maps and select models from the ensemble of solutions that are often proposed by different model fitting techniques. As a prelude, using a non-redundant and high-resolution structural dataset involving 125 permanent and 95 transient complexes, we confirm that core interface residues are conserved significantly better than nearby non-interface residues and this result is used in the cryo-EM map analysis. From the analysis of inter-component interfaces in a set of fitted models associated with low-resolution cryo-EM maps of ribosomes, chaperones and proteasomes we note that a few poorly conserved residues occur at interfaces. Interestingly a few conserved residues are not in the interface, though they are close to the interface. These observations raise the potential requirement of refitting the models in the cryo-EM maps. We show that sampling an ensemble of models and selection of models with high residue conservation at the interface and in good agreement with the density helps in improving the accuracy of the fit. This study indicates that evolutionary information can serve as an additional input to improve and validate fitting of atomic models in cryo-EM density maps.

}, issn = {1095-8657}, doi = {10.1016/j.jsb.2016.07.012}, author = {Joseph, Agnel P and Swapna, Lakshmipuram S and Rakesh, Ramachandran and Srinivasan, Narayanaswamy} } @article {5310, title = {Using the folding landscapes of proteins to understand protein function.}, journal = {Curr Opin Struct Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {67-74}, abstract = {

Proteins fold on a biologically-relevant timescale because of a funnel-shaped energy landscape. This landscape is sculpted through evolution by selecting amino-acid sequences that stabilize native interactions while suppressing stable non-native interactions that occur during folding. However, there is strong evolutionary selection for functional residues and these cannot be chosen to optimize folding. Their presence impacts the folding energy landscape in a variety of ways. Here, we survey the effects of functional residues on folding by providing several examples. We then review how such effects can be detected computationally and be used as assays for protein function. Overall, an understanding of how functional residues modulate folding should provide insights into the design of natural proteins and their homeostasis.

}, issn = {1879-033X}, doi = {10.1016/j.sbi.2016.01.001}, author = {Giri Rao, Vv Hemanth and Gosavi, Shachi} } @article {3543, title = {Wine glasses and hourglasses: Non-adaptive complexity of vesicle traffic in microbial eukaryotes.}, journal = {Mol Biochem Parasitol}, year = {2016}, month = {2016 Mar 22}, abstract = {

Microbial eukaryotes present a stunning diversity of endomembrane organization. From specialized secretory organelles such as the rhoptries and micronemes of apicomplexans, to peroxisome-derived metabolic compartments such as the glycosomes of kinetoplastids, different microbial taxa have explored different solutions to the compartmentalization and processing of cargo. The basic secretory and endocytic system, comprising the ER, Golgi, endosomes, and plasma membrane, as well as diverse taxon-specific specialized endomembrane organelles, are coupled by a complex network of cargo transport via vesicle traffic. It is tempting to connect form to function, ascribing biochemical roles to each compartment and vesicle of such a system. Here we argue that traffic systems of high complexity could arise through non-adaptive mechanisms via purely physical constraints, and subsequently be exapted for various taxon-specific functions. Our argument is based on a Boolean mathematical model of vesicle traffic: we specify rules of how compartments exchange vesicles; these rules then generate hypothetical cells with different types of endomembrane organization. Though one could imagine a large number of hypothetical vesicle traffic systems, very few of these are consistent with molecular interactions. Such molecular constraints are the bottleneck of a metaphorical hourglass, and the rules that make it through the bottleneck are expected to generate cells with many special properties. Sampling at random from among such rules represents an evolutionary null hypothesis: any properties of the resulting cells must be non-adaptive. We show by example that vesicle traffic systems generated in this random manner are reminiscent of the complex trafficking apparatus of real cells.

}, issn = {1872-9428}, doi = {10.1016/j.molbiopara.2016.03.006}, author = {Mani, Somya and Thattai, Mukund} } @article {5315, title = {σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.}, journal = {Genetics}, volume = {203}, year = {2016}, month = {2016 May}, pages = {369-85}, abstract = {

The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38{\textdegree}. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling.

}, issn = {1943-2631}, doi = {10.1534/genetics.115.183863}, author = {Choudhury, Saumitra Dey and Mushtaq, Zeeshan and Reddy-Alla, Suneel and Balakrishnan, Sruthi S and Thakur, Rajan S and Krishnan, Kozhalmannom S and Raghu, Padinjat and Ramaswami, Mani and Kumar, Vimlesh} } @article {1040, title = {161 Bridging the islands of protein families in sequence space using artificial sequences.}, journal = {J Biomol Struct Dyn}, volume = {33 Suppl 1}, year = {2015}, month = {2015}, pages = {103-4}, issn = {1538-0254}, doi = {10.1080/07391102.2015.1032798}, author = {Srinivasan, N and Mudgal, R and Kumar, G and Chandra, N R and Sowdhamini, R and Sandhya, S} } @article {1004, title = {172 Computational analysis and prediction of proteins that undergo domain swapping.}, journal = {J Biomol Struct Dyn}, volume = {33 Suppl 1}, year = {2015}, month = {2015}, pages = {112-3}, issn = {1538-0254}, doi = {10.1080/07391102.2015.1032809}, author = {Shingate, Prashant and Upadhyay, Atul and Khader, Shameer and Sowdhamini, Ramanathan} } @article {854, title = {Ancient dynamin segments capture early stages of host-mitochondrial integration.}, journal = {Proc Natl Acad Sci U S A}, volume = {112}, year = {2015}, month = {2015 Mar 3}, pages = {2800-5}, abstract = {

Eukaryotic cells use dynamins-mechano-chemical GTPases--to drive the division of endosymbiotic organelles. Here we probe early steps of mitochondrial and chloroplast endosymbiosis by tracing the evolution of dynamins. We develop a parsimony-based phylogenetic method for protein sequence reconstruction, with deep time resolution. Using this, we demonstrate that dynamins diversify through the punctuated transformation of sequence segments on the scale of secondary-structural elements. We find examples of segments that have remained essentially unchanged from the 1.8-billion-y-old last eukaryotic common ancestor to the present day. Stitching these together, we reconstruct three ancestral dynamins: The first is nearly identical to the ubiquitous mitochondrial division dynamins of extant eukaryotes, the second is partially preserved in the myxovirus-resistance--like dynamins of metazoans, and the third gives rise to the cytokinetic dynamins of amoebozoans and plants and to chloroplast division dynamins. The reconstructed sequences, combined with evolutionary models and published functional data, suggest that the ancestral mitochondrial division dynamin also mediated vesicle scission. This bifunctional protein duplicated into specialized mitochondrial and vesicle variants at least three independent times--in alveolates, green algae, and the ancestor of fungi and metazoans-accompanied by the loss of the ancient prokaryotic mitochondrial division protein FtsZ. Remarkably, many extant species that retain FtsZ also retain the predicted ancestral bifunctional dynamin. The mitochondrial division apparatus of such organisms, including amoebozoans, red algae, and stramenopiles, seems preserved in a near-primordial form.

}, keywords = {Animals, Arabidopsis, Caenorhabditis elegans, Chloroplasts, Dictyostelium, Drosophila melanogaster, Dynamins, Evolution, Molecular, Humans, Mitochondria, Mitochondrial Dynamics, Saccharomyces cerevisiae, Schizosaccharomyces}, issn = {1091-6490}, doi = {10.1073/pnas.1407163112}, author = {Purkanti, Ramya and Thattai, Mukund} } @article {858, title = {Biochemical requirements for two Dicer-like activities from wheat germ.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0116736}, abstract = {

RNA silencing pathways were first discovered in plants. Through genetic analysis, it has been established that the key silencing components called Dicer-like (DCL) genes have been shown to cooperatively process RNA substrates of multiple origin into distinct 21, 22 and 24 nt small RNAs. However, only few detailed biochemical analysis of the corresponding complexes has been carried out in plants, mainly due to the large unstable complexes that are hard to obtain or reconstitute in heterologous systems. Reconstitution of activity needs thorough understanding of all protein partners in the complex, something that is still an ongoing process in plant systems. Here, we use biochemical analysis to uncover properties of two previously identified native dicer-like activities from wheat germ. We find that standard wheat germ extract contains Dicer-like enzymes that convert double-stranded RNA (dsRNA) into two classes of small interfering RNAs of 21 and 24 nt in size. The 21 nt dicing activity, likely an siRNA producing complex known as DCL4, is 950 kDa-1.2 mDa in size and is highly unstable during purification processes but has a rather vast range for activity. On the contrary, the 24 nt dicing complex, likely the DCL3 activity, is relatively stable and comparatively smaller in size, but has stricter conditions for effective processing of dsRNA substrates. While both activities could process completely complementary dsRNA albeit with varying abilities, we show that DCL3-like 24 nt producing activity is equally good in processing incompletely complementary RNAs.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0116736}, author = {Shivaprasad, Padubidri V and Hohn, Thomas and Akbergenov, Rashid} } @article {861, title = {Biomechanical basis of wing and haltere coordination in flies.}, journal = {Proc Natl Acad Sci U S A}, volume = {112}, year = {2015}, month = {2015 Feb 3}, pages = {1481-6}, abstract = {

The spectacular success and diversification of insects rests critically on two major evolutionary adaptations. First, the evolution of flight, which enhanced the ability of insects to colonize novel ecological habitats, evade predators, or hunt prey; and second, the miniaturization of their body size, which profoundly influenced all aspects of their biology from development to behavior. However, miniaturization imposes steep demands on the flight system because smaller insects must flap their wings at higher frequencies to generate sufficient aerodynamic forces to stay aloft; it also poses challenges to the sensorimotor system because precise control of wing kinematics and body trajectories requires fast sensory feedback. These tradeoffs are best studied in Dipteran flies in which rapid mechanosensory feedback to wing motor system is provided by halteres, reduced hind wings that evolved into gyroscopic sensors. Halteres oscillate at the same frequency as and precisely antiphase to the wings; they detect body rotations during flight, thus providing feedback that is essential for controlling wing motion during aerial maneuvers. Although tight phase synchrony between halteres and wings is essential for providing proper timing cues, the mechanisms underlying this coordination are not well understood. Here, we identify specific mechanical linkages within the thorax that passively mediate both wing-wing and wing-haltere phase synchronization. We demonstrate that the wing hinge must possess a clutch system that enables flies to independently engage or disengage each wing from the mechanically linked thorax. In concert with a previously described gearbox located within the wing hinge, the clutch system enables independent control of each wing. These biomechanical features are essential for flight control in flies.

}, keywords = {Animals, Biomechanical Phenomena, Diptera, Microscopy, Electron, Scanning, Wings, Animal}, issn = {1091-6490}, doi = {10.1073/pnas.1412279112}, author = {Deora, Tanvi and Singh, Amit Kumar and Sane, Sanjay P} } @article {866, title = {Building endocytic pits without clathrin.}, journal = {Nat Rev Mol Cell Biol}, volume = {16}, year = {2015}, month = {2015 May}, pages = {311-21}, abstract = {

How endocytic pits are built in clathrin- and caveolin-independent endocytosis still remains poorly understood. Recent insight suggests that different forms of clathrin-independent endocytosis might involve the actin-driven focusing of membrane constituents, the lectin-glycosphingolipid-dependent construction of endocytic nanoenvironments, and Bin-Amphiphysin-Rvs (BAR) domain proteins serving as scaffolding modules. We discuss the need for different types of internalization processes in the context of diverse cellular functions, the existence of clathrin-independent mechanisms of cargo recruitment and membrane bending from a biological and physical perspective, and finally propose a generic scheme for the formation of clathrin-independent endocytic pits.

}, keywords = {Actins, Animals, Cell Membrane, Clathrin, Endocytosis, Humans, Lectins, Metabolic Networks and Pathways}, issn = {1471-0080}, doi = {10.1038/nrm3968}, author = {Johannes, Ludger and Parton, Robert G and Bassereau, Patricia and Mayor, Satyajit} } @article {160, title = {Bulbar microcircuit model predicts connectivity and roles of interneurons in odor coding.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0098045}, abstract = {

Stimulus encoding by primary sensory brain areas provides a data-rich context for understanding their circuit mechanisms. The vertebrate olfactory bulb is an input area having unusual two-layer dendro-dendritic connections whose roles in odor coding are unclear. To clarify these roles, we built a detailed compartmental model of the rat olfactory bulb that synthesizes a much wider range of experimental observations on bulbar physiology and response dynamics than has hitherto been modeled. We predict that superficial-layer inhibitory interneurons (periglomerular cells) linearize the input-output transformation of the principal neurons (mitral cells), unlike previous models of contrast enhancement. The linearization is required to replicate observed linear summation of mitral odor responses. Further, in our model, action-potentials back-propagate along lateral dendrites of mitral cells and activate deep-layer inhibitory interneurons (granule cells). Using this, we propose sparse, long-range inhibition between mitral cells, mediated by granule cells, to explain how the respiratory phases of odor responses of sister mitral cells can be sometimes decorrelated as observed, despite receiving similar receptor input. We also rule out some alternative mechanisms. In our mechanism, we predict that a few distant mitral cells receiving input from different receptors, inhibit sister mitral cells differentially, by activating disjoint subsets of granule cells. This differential inhibition is strong enough to decorrelate their firing rate phases, and not merely modulate their spike timing. Thus our well-constrained model suggests novel computational roles for the two most numerous classes of interneurons in the bulb.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0098045}, author = {Gilra, Aditya and Bhalla, Upinder S} } @article {2212, title = {Butterflies of India}, journal = {Indian Foundation for Butterflies}, volume = {2}, year = {2015}, url = {http://ifoundbutterflies.org/}, author = {Kunte, Krushnamegh and Roy, P and Kalesh, S. and Kodandaramaia, U} } @article {1043, title = {C9orf72 mutations may be rare in frontotemporal lobar degeneration patients in India.}, journal = {Amyotroph Lateral Scler Frontotemporal Degener}, year = {2015}, month = {2015 Oct 14}, pages = {1-3}, issn = {2167-9223}, doi = {10.3109/21678421.2015.1074706}, author = {Mukherjee, Odity and Das, Gopal and Sen, Somdutta and Dutt, Aparna and Alladi, Suvarna and Ghosh, Amitabha} } @article {1008, title = {Cellular models to study bipolar disorder: A systematic review.}, journal = {J Affect Disord}, volume = {184}, year = {2015}, month = {2015 Sep 15}, pages = {36-50}, abstract = {

BACKGROUND: There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD).

METHOD: Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients.

RESULTS: There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium.

CONCLUSION: Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations.

}, issn = {1573-2517}, doi = {10.1016/j.jad.2015.05.037}, author = {Viswanath, Biju and Jose, Sam P and Squassina, Alessio and Thirthalli, Jagadisha and Purushottam, Meera and Mukherjee, Odity and Vladimirov, Vladimir and Patrinos, George P and Del Zompo, Maria and Jain, Sanjeev} } @article {904, title = {Changing Faces of Transcriptional Regulation Reflected by Zic3.}, journal = {Curr Genomics}, volume = {16}, year = {2015}, month = {2015 Apr}, pages = {117-27}, abstract = {

The advent of genomics in the study of developmental mechanisms has brought a trove of information on gene datasets and regulation during development, where the Zic family of zinc-finger proteins plays an important role. Genomic analysis of the modes of action of Zic3 in pluripotent cells demonstrated its requirement for maintenance of stem cells pluripotency upon binding to the proximal regulatory regions (promoters) of genes associated with cell pluripotency (Nanog, Sox2, Oct4, etc.) as well as cell cycle, proliferation, oncogenesis and early embryogenesis. In contrast, during gastrulation and neurulation Zic3 acts by binding the distal regulatory regions (enhancers, etc) associated with control of gene transcription in the Nodal and Wnt signaling pathways, including genes that act to break body symmetry. This illustrates a general role of Zic3 as a transcriptional regulator that acts not only alone, but in many instances in conjunction with other transcription factors. The latter is done by binding to adjacent sites in the context of multi-transcription factor complexes associated with regulatory elements.

}, issn = {1389-2029}, doi = {10.2174/1389202916666150205124519}, author = {Winata, Cecilia Lanny and Kondrychyn, Igor and Korzh, Vladimir} } @article {1621, title = {Characterization of the finch embryo supports evolutionary conservation of the naive stage of development in amniotes.}, journal = {Elife}, volume = {4}, year = {2015}, month = {2015}, pages = {e07178}, abstract = {

Innate pluripotency of mouse embryos transits from naive to primed state as the inner cell mass differentiates into epiblast. In vitro, their counterparts are embryonic (ESCs) and epiblast stem cells (EpiSCs), respectively. Activation of the FGF signaling cascade results in mouse ESCs differentiating into mEpiSCs, indicative of its requirement in the shift between these states. However, only mouse ESCs correspond to the naive state; ESCs from other mammals and from chick show primed state characteristics. Thus, the significance of the naive state is unclear. In this study, we use zebra finch as a model for comparative ESC studies. The finch blastoderm has mESC-like properties, while chick blastoderm exhibits EpiSC features. In the absence of FGF signaling, finch cells retained expression of pluripotent markers, which were lost in cells from chick or aged finch epiblasts. Our data suggest that the naive state of pluripotency is evolutionarily conserved among amniotes.

}, issn = {2050-084X}, doi = {10.7554/eLife.07178}, author = {Mak, Siu-Shan and Alev, Cantas and Nagai, Hiroki and Wrabel, Anna and Matsuoka, Yoko and Honda, Akira and Sheng, Guojun and Ladher, Raj K} } @article {874, title = {Collation and analyses of DNA-binding protein domain families from sequence and structural databanks.}, journal = {Mol Biosyst}, volume = {11}, year = {2015}, month = {2015 Apr}, pages = {1110-8}, abstract = {

DNA-protein interactions govern several high fidelity cellular processes like DNA-replication, transcription, DNA repair, etc. Proteins that have the ability to recognise and bind DNA sequences can be classified either according to their DNA-binding motif or based on the sequence of the target nucleotides. We have collated the DNA-binding families by integrating information from both protein sequence family and structural databases. This resulted in a dataset of 1057 DNA-binding protein domain families. Their family properties (the number of members, percent identity distribution and length of members) and domain architectures were examined. Further, sequence domain families were mapped to structures in the protein databank (PDB) and the protein domain structure classification database (SCOP). The DNA-binding families, with no structural information, were clustered together into potential superfamilies based on sequence associations. On the basis of functions attributed to DNA-binding protein folds, we observe that a majority of the DNA-binding proteins follow divergent evolution. This study can serve as a basis for annotation and distribution of DNA-binding proteins in genome(s) of interest. The entire collated set of DNA-binding protein domains is available for download as Hidden Markov Models.

}, keywords = {Archaeal Proteins, Bacterial Proteins, Databases, Protein, DNA-Binding Proteins, Protein Structure, Tertiary, Viral Proteins}, issn = {1742-2051}, doi = {10.1039/c4mb00629a}, author = {Malhotra, Sony and Sowdhamini, Ramanathan} } @article {906, title = {Combined collapse by bridging and self-adhesion in a prototypical polymer model inspired by the bacterial nucleoid.}, journal = {Soft Matter}, volume = {11}, year = {2015}, month = {2015 Mar 7}, pages = {1677-87}, abstract = {

Recent experimental results suggest that the E. coli chromosome feels a self-attracting interaction of osmotic origin, and is condensed in foci by bridging interactions. Motivated by these findings, we explore a generic modeling framework combining solely these two ingredients, in order to characterize their joint effects. Specifically, we study a simple polymer physics computational model with weak ubiquitous short-ranged self attraction and stronger sparse bridging interactions. Combining theoretical arguments and simulations, we study the general phenomenology of polymer collapse induced by these dual contributions, in the case of regularly spaced bridging. Our results distinguish a regime of classical Flory-like coil-globule collapse dictated by the interplay of excluded volume and attractive energy and a switch-like collapse where bridging interactions compete with entropy loss terms from the looped arms of a star-like rosette. Additionally, we show that bridging can induce stable compartmentalized domains. In these configurations, different "cores" of bridging proteins are kept separated by star-like polymer loops in an entropically favorable multi-domain configuration, with a mechanism that parallels micellar polysoaps. Such compartmentalized domains are stable, and do not need any intra-specific interactions driving their segregation. Domains can be stable also in the presence of uniform attraction, as long as the uniform collapse is above its theta point.

}, keywords = {Chromosomes, Bacterial, Escherichia coli, Models, Chemical, Polymers}, issn = {1744-6848}, doi = {10.1039/c4sm02434f}, author = {Scolari, Vittore F and Cosentino Lagomarsino, Marco} } @article {910, title = {Commensalism facilitates gene flow in mountains: a comparison between two Rattus species.}, journal = {Heredity (Edinb)}, volume = {115}, year = {2015}, month = {2015 Sep}, pages = {253-61}, abstract = {

Small mammal dispersal is strongly affected by geographical barriers. However, commensal small mammals may be passively transported over large distances and strong barriers by humans (often with agricultural products). This pattern should be especially apparent in topographically complex landscapes, such as mountain ranges, where valleys and/or peaks can limit dispersal of less vagile species. We predict that commensal species would have lower genetic differentiation and higher migration rates than related non-commensals in such landscapes. We contrasted population genetic differentiation in two sympatric Rattus species (R. satarae and R. rattus) in the Western Ghats mountains in southern India. We sampled rats from villages and adjacent forests in seven locations (20-640 km apart). Capture-based statistics confirmed that R. rattus is abundant in human settlements in this region, whereas R. satarae is non-commensal and found mostly in forests. Population structure analyses using ~970-bp mitochondrial control region and 17 microsatellite loci revealed higher differentiation for the non-commensal species (R. satarae F-statistics=0.420, 0.065, R. rattus F-statistics=0.195, 0.034; mitochondrial DNA, microsatellites, respectively). Genetic clustering analyses confirm that clusters in R. satarae are more distinct and less admixed than those in R. rattus. R. satarae shows higher slope for isolation-by-distance compared with R. rattus. Although mode of migration estimates do not strongly suggest higher rates in R. rattus than in R. satarae, they indicate that migration over long distances could still be higher in R. rattus. We suggest that association with humans could drive the observed pattern of differentiation in the commensal R. rattus, consequently impacting not only their dispersal abilities, but also their evolutionary trajectories.

}, keywords = {Animal Distribution, Animals, Cluster Analysis, DNA, Mitochondrial, Ecosystem, Gene Flow, Genetic Variation, Genetics, Population, Geography, India, Microsatellite Repeats, Molecular Sequence Data, Rats, Sequence Analysis, DNA, Sympatry}, issn = {1365-2540}, doi = {10.1038/hdy.2015.34}, author = {Varudkar, A and Ramakrishnan, U} } @article {994, title = {Comparative molecular species delimitation in the charismatic Nawab butterflies (Nymphalidae, Charaxinae, Polyura).}, journal = {Mol Phylogenet Evol}, volume = {91}, year = {2015}, month = {2015 Oct}, pages = {194-209}, abstract = {

The charismatic tropical Polyura Nawab butterflies are distributed across twelve biodiversity hotspots in the Indomalayan/Australasian archipelago. In this study, we tested an array of species delimitation methods and compared the results to existing morphology-based taxonomy. We sequenced two mitochondrial and two nuclear gene fragments to reconstruct phylogenetic relationships within Polyura using both Bayesian inference and maximum likelihood. Based on this phylogenetic framework, we used the recently introduced bGMYC, BPP and PTP methods to investigate species boundaries. Based on our results, we describe two new species Polyura paulettae Toussaint sp. n. and Polyura smilesi Toussaint sp. n., propose one synonym, and five populations are raised to species status. Most of the newly recognized species are single-island endemics likely resulting from the recent highly complex geological history of the Indomalayan-Australasian archipelago. Surprisingly, we also find two newly recognized species in the Indomalayan region where additional biotic or abiotic factors have fostered speciation. Species delimitation methods were largely congruent and succeeded to cross-validate most extant morphological species. PTP and BPP seem to yield more consistent and robust estimations of species boundaries with respect to morphological characters while bGMYC delivered contrasting results depending on the different gene trees considered. Our findings demonstrate the efficiency of comparative approaches using molecular species delimitation methods on empirical data. They also pave the way for the investigation of less well-known groups to unveil patterns of species richness and catalogue Earth{\textquoteright}s concealed, therefore unappreciated diversity.

}, issn = {1095-9513}, doi = {10.1016/j.ympev.2015.05.015}, author = {Toussaint, Emmanuel F A and Morini{\`e}re, J{\'e}r{\^o}me and M{\"u}ller, Chris J and Kunte, Krushnamegh and Turlin, Bernard and Axel Hausmann and Balke, Michael} } @article {995, title = {Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0131077}, abstract = {

Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0131077}, author = {Harini, K and Sowdhamini, Ramanathan} } @article {1017, title = {Conserved hippocampal cellular pathophysiology but distinct behavioural deficits in a new rat model of FXS.}, journal = {Hum Mol Genet}, volume = {24}, year = {2015}, month = {2015 Nov 1}, pages = {5977-84}, abstract = {

Recent advances in techniques for manipulating genomes have allowed the generation of transgenic animals other than mice. These new models enable cross-mammalian comparison of neurological disease from core cellular pathophysiology to circuit and behavioural endophenotypes. Moreover they will enable us to directly test whether common cellular dysfunction or behavioural outcomes of a genetic mutation are more conserved across species. Using a new rat model of Fragile X Syndrome, we report that Fmr1 knockout (KO) rats exhibit elevated basal protein synthesis and an increase in mGluR-dependent long-term depression in CA1 of the hippocampus that is independent of new protein synthesis. These defects in plasticity are accompanied by an increase in dendritic spine density selectively in apical dendrites and subtle changes in dendritic spine morphology of CA1 pyramidal neurons. Behaviourally, Fmr1 KO rats show deficits in hippocampal-dependent, but not hippocampal-independent, forms of associative recognition memory indicating that the loss of fragile X mental retardation protein (FMRP) causes defects in episodic-like memory. In contrast to previous reports from mice, Fmr1 KO rats show no deficits in spatial reference memory reversal learning. One-trial spatial learning in a delayed matching to place water maze task was also not affected by the loss of FMRP in rats. This is the first evidence for conservation across mammalian species of cellular and physiological hippocampal phenotypes associated with the loss of FMRP. Furthermore, while key cellular phenotypes are conserved they manifest in distinct behavioural dysfunction. Finally, our data reveal novel information about the selective role of FMRP in hippocampus-dependent associative memory.

}, issn = {1460-2083}, doi = {10.1093/hmg/ddv299}, author = {Till, Sally M and Asiminas, Antonis and Jackson, Adam D and Katsanevaki, Danai and Barnes, Stephanie A and Osterweil, Emily K and Bear, Mark F and Chattarji, Sumantra and Wood, Emma R and Wyllie, David J A and Kind, Peter C} } @article {899, title = {Construction and validation of an atomic model for bacterial TSPO from electron microscopy density, evolutionary constraints, and biochemical and biophysical data.}, journal = {Biochim Biophys Acta}, volume = {1848}, year = {2015}, month = {2015 Feb}, pages = {568-80}, abstract = {

The 18 kDa protein TSPO is a highly conserved transmembrane protein found in bacteria, yeast, animals and plants. TSPO is involved in a wide range of physiological functions, among which the transport of several molecules. The atomic structure of monomeric ligand-bound mouse TSPO in detergent has been published recently. A previously published low-resolution structure of Rhodobacter sphaeroides TSPO, obtained from tubular crystals with lipids and observed in cryo-electron microscopy, revealed an oligomeric structure without any ligand. We analyze this electron microscopy density in view of available biochemical and biophysical data, building a matching atomic model for the monomer and then the entire crystal. We compare its intra- and inter-molecular contacts with those predicted by amino acid covariation in TSPO proteins from evolutionary sequence analysis. The arrangement of the five transmembrane helices in a monomer of our model is different from that observed for the mouse TSPO. We analyze possible ligand binding sites for protoporphyrin, for the high-affinity ligand PK 11195, and for cholesterol in TSPO monomers and/or oligomers, and we discuss possible functional implications.

}, keywords = {Amino Acid Sequence, Bacterial Proteins, Binding Sites, Carrier Proteins, Cholesterol, Conserved Sequence, Cryoelectron Microscopy, Crystallization, Isoquinolines, Ligands, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Multimerization, Protein Structure, Secondary, Protoporphyrins, Rhodobacter sphaeroides, Sequence Alignment}, issn = {0006-3002}, doi = {10.1016/j.bbamem.2014.10.028}, author = {Hinsen, Konrad and Vaitinadapoule, Aurore and Ostuni, Mariano A and Etchebest, Catherine and Lacapere, Jean-Jacques} } @article {1024, title = {Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat.}, journal = {Database (Oxford)}, volume = {2015}, year = {2015}, month = {2015}, pages = {bav063}, abstract = {

During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.

}, issn = {1758-0463}, doi = {10.1093/database/bav063}, author = {Babbitt, Patricia C and Bagos, Pantelis G and Bairoch, Amos and Bateman, Alex and Chatonnet, Arnaud and Chen, Mark Jinan and Craik, David J and Finn, Robert D and Gloriam, David and Haft, Daniel H and Henrissat, Bernard and Holliday, Gemma L and Isberg, Vignir and Kaas, Quentin and Landsman, David and Lenfant, Nicolas and Manning, Gerard and Nagano, Nozomi and Srinivasan, Narayanaswamy and O{\textquoteright}Donovan, Claire and Pruitt, Kim D and Sowdhamini, Ramanathan and Rawlings, Neil D and Saier, Milton H and Sharman, Joanna L and Spedding, Michael and Tsirigos, Konstantinos D and Vastermark, Ake and Vriend, Gerrit} } @article {893, title = {Cryptic diversity and habitat partitioning in an economically important aphid species complex.}, journal = {Infect Genet Evol}, volume = {30}, year = {2015}, month = {2015 Mar}, pages = {230-7}, abstract = {

Cardamom Bushy Dwarf Virus (CBDV) is an aphid-borne nanovirus which infects large cardamom, Amomum subulatum (Zingiberaceae family), in the Himalayan foothills of Northeast India, Nepal and Bhutan. Two aphid species have been reported to transmit CBDV, including Pentalonia nigronervosa and Micromyzus kalimpongensis (also described as Pentalonia kalimpongensis). However, P. nigronervosa was recently split into two species which exhibit different host plant affiliations. Whilst P. nigronervosa primarily feeds on banana plants, Pentaloniacaladii (previously considered a {\textquoteright}form{\textquoteright} of P. nigronervosa) typically feeds on plants belonging to the Araceae, Heliconiaceae and Zingiberaceae families. This raises the possibility that CBDV vectors that were originally described as P. nigronervosa correspond to P. caladii. Accurate identification of vector species is important for understanding disease dynamics and for implementing management strategies. However, closely related species can be difficult to distinguish based on morphological characteristics. In this study, we used molecular markers (two mitochondrial loci and one nuclear locus) and Bayesian phylogenetic analyses to identify aphid specimens collected from 148 CBDV infected plants at a range of locations and elevations throughout Sikkim and the Darjeeling district of West Bengal (Northeast India). Our results revealed the presence of a diversity of lineages, comprising up to six distinct species in at least two related genera. These included the three species mentioned above, an unidentified Pentalonia species and two lineages belonging to an unknown genus. Surprisingly, P. caladii was only detected on a single infected plant, indicating that this species may not play an important role in CBDV transmission dynamics. Distinct elevation distributions were observed for the different species, demonstrating that the community composition of aphids which feed on large cardamom plants changes across an elevation gradient. This has implications for understanding how competent vector species could influence spatial and temporal transmission patterns of CBDV.

}, keywords = {Animals, Aphids, Babuvirus, Ecosystem, Elettaria, India, Insect Vectors, Musa, Phylogeny, Plant Diseases}, issn = {1567-7257}, doi = {10.1016/j.meegid.2014.12.020}, author = {Savory, F R and Ramakrishnan, U} } @article {896, title = {Cytoskeletal control of nuclear morphology and chromatin organization.}, journal = {J Mol Biol}, volume = {427}, year = {2015}, month = {2015 Feb 13}, pages = {695-706}, abstract = {

The nucleus is sculpted toward various morphologies during cellular differentiation and development. Alterations in nuclear shape often result in changes to chromatin organization and genome function. This is thought to be reflective of its role as a cellular mechanotransducer. Recent evidence has highlighted the importance of cytoskeletal organization in defining how nuclear morphology regulates chromatin dynamics. However, the mechanisms underlying cytoskeletal control of chromatin remodeling are not well understood. We demonstrate here the differential influence of perinuclear actin- and microtubule-driven assemblies on nuclear architecture using pharmacological inhibitors and targeted RNA interference knockdown of cytoskeleton components in Drosophila cells. We find evidence that the loss of perinuclear actin assembly results in basolateral enhancement of microtubule organization and this is reflected functionally by enhanced nuclear dynamics. Cytoskeleton reorganization leads to nuclear lamina deformation that influences heterochromatin localization and core histone protein mobility. We also show that modulations in actin-microtubule assembly result in differential gene expression patterns. Taken together, we suggest that perinuclear actin and basolateral microtubule organization exerts mechanical control on nuclear morphology and chromatin dynamics.

}, keywords = {Actins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, Cytoskeleton, Drosophila melanogaster, Gene Expression Regulation, Histones, Mechanotransduction, Cellular, Nuclear Proteins}, issn = {1089-8638}, doi = {10.1016/j.jmb.2014.09.008}, author = {Ramdas, Nisha M and Shivashankar, G V} } @article {1005, title = {Deep and wide valleys drive nested phylogeographic patterns across a montane bird community.}, journal = {Proc Biol Sci}, volume = {282}, year = {2015}, month = {2015 Jul 7}, abstract = {

Montane species distributions interrupted by valleys can lead to range fragmentation, differentiation and ultimately speciation. Paleoclimatic fluctuations may accentuate or reduce such diversification by temporally altering the extent of montane habitat and may affect species differentially. We examined how an entire montane bird community of the Western Ghats--a linear, coastal tropical mountain range--responds to topographic valleys that host different habitats. Using genetic data from 23 species (356 individuals) collected across nine locations, we examined if different species in the community reveal spatial concordance in population differentiation, and whether the timing of these divergences correlate with climatic events. Our results reveal a nested effect of valleys, with several species (10 of 23) demonstrating the oldest divergences associated with the widest and deepest valley in the mountain range, the Palghat Gap. Further, a subset of these 10 species revealed younger divergences across shallower, narrower valleys. We recovered discordant divergence times for all valley-affected montane birds, mostly in the Pleistocene, supporting the Pliestocene-pump hypotheses and highlighting the role of climatic fluctuations during this period in driving species evolution. A majority of species remain unaffected by valleys, perhaps owing to geneflow or extinction-recolonization dynamics. Studying almost the entire community allowed us to uncover a range of species{\textquoteright} responses, including some generalizable and other unpredicted patterns.

}, issn = {1471-2954}, doi = {10.1098/rspb.2015.0861}, author = {Robin, V V and Vishnudas, C K and Gupta, Pooja and Ramakrishnan, Uma} } @article {915, title = {Design of ultrasensitive DNA-based fluorescent pH sensitive nanodevices.}, journal = {Nanoscale}, volume = {7}, year = {2015}, month = {2015 Jun 14}, pages = {10008-12}, abstract = {

Here we tune the pH sensitivity of a DNA-based conformational switch, called the I-switch, to yield a set of fluorescent pH sensitive nanodevices with a collective, expanded pH sensing regime from 5.3 to 7.5. The expanded pH regime of this new family of I-switches originates from a dramatic improvement in the overall percentage signal change in response to pH of these nanodevices.

}, issn = {2040-3372}, doi = {10.1039/c5nr01158b}, author = {Halder, Saheli and Krishnan, Yamuna} } @article {1035, title = {Designing DNA nanodevices for compatibility with the immune system of higher organisms.}, journal = {Nat Nanotechnol}, volume = {10}, year = {2015}, month = {2015 Sep}, pages = {741-7}, abstract = {

DNA is proving to be a powerful scaffold to construct molecularly precise designer DNA devices. Recent trends reveal their ever-increasing deployment within living systems as delivery devices that not only probe but also program and re-program a cell, or even whole organisms. Given that DNA is highly immunogenic, we outline the molecular, cellular and organismal response pathways that designer nucleic acid nanodevices are likely to elicit in living systems. We address safety issues applicable when such designer DNA nanodevices interact with the immune system. In light of this, we discuss possible molecular programming strategies that could be integrated with such designer nucleic acid scaffolds to either evade or stimulate the host response with a view to optimizing and widening their applications in higher organisms.

}, issn = {1748-3395}, doi = {10.1038/nnano.2015.180}, author = {Surana, Sunaina and Shenoy, Avinash R and Krishnan, Yamuna} } @article {1015, title = {Differential Distortion of Purine Substrates by Human and Plasmodium falciparum Hypoxanthine-Guanine Phosphoribosyltransferase to Catalyse the Formation of Mononucleotides.}, journal = {Chemphyschem}, volume = {16}, year = {2015}, month = {2015 Jul 20}, pages = {2172-81}, abstract = {

Plasmodium falciparum (Pf) hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a potential therapeutic target. Compared to structurally homologous human enzymes, it has expanded substrate specificity. In this study, 9-deazapurines are used as in situ probes of the active sites of human and Pf HGPRTs. Through the use of these probes it is found that non-covalent interactions stabilise the pre-transition state of the HGPRT-catalysed reaction. Vibrational spectra reveal that the bound substrates are extensively distorted, the carbonyl bond of nucleobase moiety is weakened and the substrate is destabilised along the reaction coordinate. Raman shifts of the human and Pf enzymes are used to quantify the differing degrees of hydrogen bonding in the homologues. A decreased Raman cross-section in enzyme-bound 9-deazaguanine (9DAG) shows that the phenylalanine residue (Phe186 in human and Phe197 in Pf) of HGPRT stacks with the nucleobase. Differential loss of the Raman cross-section suggests that the active site is more compact in human HGPRT as compared to the Pf enzyme, and is more so in the phosphoribosyl pyrophosphate (PRPP) complex 9DAG-PRPP-HGPRT than in 9-deazahypoxanthine (9DAH)-PRPP-HGPRT.

}, issn = {1439-7641}, doi = {10.1002/cphc.201500084}, author = {Karnawat, Vishakha and Gogia, Spriha and Balaram, Hemalatha and Puranik, Mrinalini} } @article {1019, title = {Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin.}, journal = {Mol Biol Cell}, volume = {26}, year = {2015}, month = {2015 Nov 5}, pages = {4033-45}, abstract = {

Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24-37{\textdegree}C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature-dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI-anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an "active actin-membrane composite" cell surface.

}, issn = {1939-4586}, doi = {10.1091/mbc.E15-06-0397}, author = {Saha, Suvrajit and Lee, Il-Hyung and Polley, Anirban and Groves, Jay T and Rao, Madan and Mayor, Satyajit} } @article {869, title = {DOCKSCORE: a webserver for ranking protein-protein docked poses.}, journal = {BMC Bioinformatics}, volume = {16}, year = {2015}, month = {2015}, pages = {127}, abstract = {

BACKGROUND: Proteins interact with a variety of other molecules such as nucleic acids, small molecules and other proteins inside the cell. Structure-determination of protein-protein complexes is challenging due to several reasons such as the large molecular weights of these macromolecular complexes, their dynamic nature, difficulty in purification and sample preparation. Computational docking permits an early understanding of the feasibility and mode of protein-protein interactions. However, docking algorithms propose a number of solutions and it is a challenging task to select the native or near native pose(s) from this pool. DockScore is an objective scoring scheme that can be used to rank protein-protein docked poses. It considers several interface parameters, namely, surface area, evolutionary conservation, hydrophobicity, short contacts and spatial clustering at the interface for scoring.

RESULTS: We have implemented DockScore in form of a webserver for its use by the scientific community. DockScore webserver can be employed, subsequent to docking, to perform scoring of the docked solutions, starting from multiple poses as inputs. The results, on scores and ranks for all the poses, can be downloaded as a csv file and graphical view of the interface of best ranking poses is possible.

CONCLUSIONS: The webserver for DockScore is made freely available for the scientific community at: http://caps.ncbs.res.in/dockscore/ .

}, keywords = {Algorithms, Humans, Internet, Molecular Docking Simulation, Protein Binding, Protein Interaction Domains and Motifs, Proteins, ras GTPase-Activating Proteins, Software}, issn = {1471-2105}, doi = {10.1186/s12859-015-0572-6}, author = {Malhotra, Sony and Mathew, Oommen K and Sowdhamini, Ramanathan} } @article {877, title = {A dPIP5K dependent pool of phosphatidylinositol 4,5 bisphosphate (PIP2) is required for G-protein coupled signal transduction in Drosophila photoreceptors.}, journal = {PLoS Genet}, volume = {11}, year = {2015}, month = {2015 Jan}, pages = {e1004948}, abstract = {

Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes.

}, keywords = {Animals, Cell Membrane, Cytoskeleton, Drosophila, Drosophila melanogaster, Light Signal Transduction, Membrane Proteins, Ocular Physiological Phenomena, Phosphatidylinositol 4,5-Diphosphate, Phosphoinositide Phospholipase C, Phosphotransferases (Alcohol Group Acceptor), Photoreceptor Cells, Retina, Signal Transduction}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1004948}, author = {Chakrabarti, Purbani and Kolay, Sourav and Yadav, Shweta and Kumari, Kamalesh and Nair, Amit and Trivedi, Deepti and Raghu, Padinjat} } @article {909, title = {The dynamic impact of repeated stress on the hippocampal spatial map.}, journal = {Hippocampus}, volume = {25}, year = {2015}, month = {2015 Jan}, pages = {38-50}, abstract = {

Stress alters the function of many physiological processes throughout the body, including in the brain. A neural circuit particularly vulnerable to the effects of stress is the hippocampus, a key component of the episodic and spatial memory system in both humans and rodents. Earlier studies have provided snapshots of morphological, molecular, physiological and behavioral changes in the hippocampus following either acute or repeated stress. However, the cumulative impact of repeated stress on in vivo hippocampal physiology remains unexplored. Here we report the stress-induced modulation of the spatially receptive fields of the hippocampal CA1 {\textquoteright}place cells{\textquoteright} as mice explore familiar and novel tracks after 5 and 10 days of immobilization stress. We find that similar to what has been observed following acute stress, five days of repeated stress results in decreased excitability of CA1 pyramidal cells. Following ten days of chronic stress, however, this decreased hippocampal excitability is no longer evident, suggesting adaptation may have occurred. In addition to these changes in neuronal excitability, we find deficient context discrimination, wherein both short-term and chronic stress impair the ability of the hippocampus to unambiguously distinguish novel and familiar environments. These results suggest that a loss of network flexibility may underlie some of the behavioral deficits accompanying chronic stress.

}, keywords = {Animals, Behavior, Animal, CA1 Region, Hippocampal, Discrimination (Psychology), Generalization (Psychology), Male, Mice, Mice, Inbred C57BL, Spatial Memory, Stress, Psychological, Time Factors}, issn = {1098-1063}, doi = {10.1002/hipo.22348}, author = {Tomar, Anupratap and Polygalov, Denis and Chattarji, Sumantra and McHugh, Thomas J} } @article {1038, title = {Dynamical feature extraction at the sensory periphery guides chemotaxis.}, journal = {Elife}, volume = {4}, year = {2015}, month = {2015}, abstract = {

Behavioral strategies employed for chemotaxis have been described across phyla, but the sensorimotor basis of this phenomenon has seldom been studied in naturalistic contexts. Here, we examine how signals experienced during free olfactory behaviors are processed by first-order olfactory sensory neurons (OSNs) of the Drosophila larva. We find that OSNs can act as differentiators that transiently normalize stimulus intensity-a property potentially derived from a combination of integral feedback and feed-forward regulation of olfactory transduction. In olfactory virtual reality experiments, we report that high activity levels of the OSN suppress turning, whereas low activity levels facilitate turning. Using a generalized linear model, we explain how peripheral encoding of olfactory stimuli modulates the probability of switching from a run to a turn. Our work clarifies the link between computations carried out at the sensory periphery and action selection underlying navigation in odor gradients.

}, issn = {2050-084X}, doi = {10.7554/eLife.06694}, author = {Schulze, Aljoscha and Gomez-Marin, Alex and Rajendran, Vani G and Lott, Gus and Musy, Marco and Ahammad, Parvez and Deogade, Ajinkya and Sharpe, James and Riedl, Julia and Jarriault, David and Trautman, Eric T and Werner, Christopher and Venkadesan, Madhusudhan and Druckmann, Shaul and Jayaraman, Vivek and Louis, Matthieu} } @article {5221, title = {Ecosystem monitoring and forest census studies in South Asia (Meeting Report)}, journal = {Current Science}, volume = {180}, year = {2015}, month = {2015}, pages = {1779 {\textendash} 1782}, author = {Marthews, T. R. and Nelaballi, S. and Ratnam, J. and Sankaran, M.} } @article {1003, title = {The effect of land-use on the diversity and mass-abundance relationships of understory avian insectivores in Sri Lanka and southern India.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {11569}, abstract = {

Understory avian insectivores are especially sensitive to deforestation, although regional differences in how these species respond to human disturbance may be linked to varying land-use histories. South Asia experienced widespread conversion of forest to agriculture in the nineteenth century, providing a comparison to tropical areas deforested more recently. In Sri Lanka and the Western Ghats of India, we compared understory insectivores to other guilds, and to insectivores with different vertical strata preferences, both inside mixed-species flocks and for the whole bird community. Overall species richness did not change across the land-use gradient, although there was substantial turnover in species composition between land-use types. We found that the proportion of species represented by insectivores was ~1.14 times higher in forest compared to agriculture, and the proportion of insectivores represented by understory species was ~1.32 times higher in forests. Mass-abundance relationships were very different when analyzed on mixed-species flocks compared to the total community, perhaps indicating reduced competition in these mutualisms. We show that South Asia fits the worldwide pattern of understory insectivores declining with increased land-use intensity, and conclude that these species can be used globally as indicator and/or umbrella species for conservation across different disturbance time scales.

}, issn = {2045-2322}, doi = {10.1038/srep11569}, author = {Sreekar, Rachakonda and Srinivasan, Umesh and Mammides, Christos and Chen, Jin and Manage Goodale, Uromi and Kotagama, Sarath Wimalabandara and Sidhu, Swati and Goodale, Eben} } @article {997, title = {Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {12186}, abstract = {

Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution.

}, issn = {2045-2322}, doi = {10.1038/srep12186}, author = {Hansen, Sabine and Krishna, Sandeep and Semsey, Szabolcs and Svenningsen, Sine Lo} } @article {1010, title = {Energetic Calculations to Decipher pH-Dependent Oligomerization and Domain Swapping of Proteins.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0127716}, abstract = {

Domain swapping mechanism is a specialised mode of oligomerization of proteins in which part of a protein is exchanged in a non-covalent manner between constituent subunits. This mechanism is highly affected by several physiological conditions. Here, we present a detailed analysis ofthe effect of pH on different regions of the domain swapped oligomer by considering examples which are known to be sensitive to pH in transiting from monomeric to domain-swapped dimeric form. The energetic calculations were performed using a specialized method which considers changes in pH and subsequent changes in the interactions between subunits. This analysis provides definitive hints about the pH-dependence switch from monomer to domain-swapped oligomer and the steps that may be involved in the swapping mechanism.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0127716}, author = {Shingate, Prashant and Warwicker, Jim and Sowdhamini, Ramanathan} } @article {908, title = {Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: insights into structure and function.}, journal = {Tuberculosis (Edinb)}, volume = {95}, year = {2015}, month = {2015 Jan}, pages = {14-25}, abstract = {

The availability of the genome sequence of Mycobacterium tuberculosis H37Rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in M. tuberculosis remain unknown. The emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95\% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. New information includes association of 244 proteins with 205 domain families and a separate set of new association of folds to 64 proteins. Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. In retrospect, such superfamily relationships have facilitated recognition of probable structure and/or function for several uncharacterized protein families, eventually aiding recognition of probable functions for homologous proteins corresponding to such families. Gene products unique to mycobacteria for which no functions could be identified are 183. Of these 18 were determined to be M. tuberculosis specific. Such pathogen-specific proteins are speculated to harbour virulence factors required for pathogenesis. A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery.

}, keywords = {Hydrolases, Mycobacterium tuberculosis, Protein Structure, Tertiary, Proteome, Sequence Analysis, Protein, Structural Homology, Protein}, issn = {1873-281X}, doi = {10.1016/j.tube.2014.10.009}, author = {Ramakrishnan, Gayatri and Ochoa-Monta{\~n}o, Bernardo and Raghavender, Upadhyayula S and Mudgal, Richa and Joshi, Adwait G and Chandra, Nagasuma R and Sowdhamini, Ramanathan and Blundell, Tom L and Srinivasan, Narayanaswamy} } @article {1000, title = {Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold.}, journal = {Proteins}, volume = {83}, year = {2015}, month = {2015 Oct}, pages = {1766-86}, abstract = {

Heterodimeric proteins with homologous subunits of same fold are involved in various biological processes. The objective of this study is to understand the evolution of structural and functional features of such heterodimers. Using a non-redundant dataset of 70 such heterodimers of known 3D structure and an independent dataset of 173 heterodimers from yeast, we note that the mean sequence identity between interacting homologous subunits is only 23-24\% suggesting that, generally, highly diverged paralogues assemble to form such a heterodimer. We also note that the functional roles of interacting subunits/domains are generally quite different. This suggests that, though the interacting subunits/domains are homologous, the high evolutionary divergence characterize their high functional divergence which contributes to a gross function for the heterodimer considered as a whole. The inverse relationship between sequence identity and RMSD of interacting homologues in heterodimers is not followed. We also addressed the question of formation of homodimers of the subunits of heterodimers by generating models of fictitious homodimers on the basis of the 3D structures of the heterodimers. Interaction energies associated with these homodimers suggests that, in overwhelming majority of the cases, such homodimers are unlikely to be stable. Majority of the homologues of heterodimers of known structures form heterodimers (51.8\%) and a small proportion (14.6\%) form homodimers. Comparison of 3D structures of heterodimers with homologous homodimers suggests that interfacial nature of residues is not well conserved. In over 90\% of the cases we note that the interacting subunits of heterodimers are co-localized in the cell.

}, issn = {1097-0134}, doi = {10.1002/prot.24849}, author = {Sudha, Govindarajan and Naveenkumar, Nagarajan and Srinivasan, Narayanaswamy} } @article {2209, title = {Evolutionary Biology}, journal = {Current Science}, volume = {108}, year = {2015}, pages = {1835-1873}, author = {Kunte, Krushnamegh and Agashe, Deepa} } @article {871, title = {Expression and purification of OsVDAC4.}, journal = {Methods Enzymol}, volume = {556}, year = {2015}, month = {2015}, pages = {51-75}, abstract = {

The voltage-dependent anion channel (VDAC), a major component of the mitochondrial outer membrane, has emerged as an important player in cell function, survival, and death signaling. VDAC function is modulated by its interaction with proteins such as hexokinase, adenine nucleotide translocator, and apoptotic proteins like Bax. Monitoring the activity of VDAC and its modulation in the complex cellular milieu is fraught with complications. Minimizing the number of components in the study is one approach to teasing apart various aspects of its function. In this chapter, we have described detailed protocols for the purification of a rice VDAC isoform, OsVDAC4 after overexpression in a bacterial system. The protein is solubilized with LDAO and then reconstituted into liposomes or planar bilayers to verify its competence to fold into a functionally active form.

}, issn = {1557-7988}, doi = {10.1016/bs.mie.2014.12.019}, author = {Godbole, Ashwini and Dubey, Ashvini K and Mitra, Rohan and Reddy, Palakolanu S and Mathew, M K} } @article {916, title = {Fast, Efficient, and Stable Conjugation of Multiple DNA Strands on Colloidal Quantum Dots.}, journal = {Bioconjug Chem}, volume = {26}, year = {2015}, month = {2015 Aug 19}, pages = {1582-9}, abstract = {

A novel method for covalent conjugation of DNA to polymer coated quantum dots (QDs) is investigated in detail. This method is fast and efficient: up to 12 DNA strands can be covalently conjugated per QD in optimized reaction conditions. The QD-DNA conjugates can be purified using size exclusion chromatography and the QDs retain high quantum yield and excellent stability after DNA coupling. We explored single-stranded and double-stranded DNA coupling, as well as various lengths. We show that the DNA coupling is most efficient for short (15 mer) single-stranded DNA. The DNA coupling has been performed on QDs emitting at four different wavelengths, as well as on gold nanoparticles, suggesting that this technique can be generalized to a wide range of nanoparticles.

}, issn = {1520-4812}, doi = {10.1021/acs.bioconjchem.5b00221}, author = {Banerjee, Anusuya and Grazon, Chlo{\'e} and Nadal, Brice and Pons, Thomas and Krishnan, Yamuna and Dubertret, Benoit} } @article {897, title = {Fast native-SAD phasing for routine macromolecular structure determination.}, journal = {Nat Methods}, volume = {12}, year = {2015}, month = {2015 Feb}, pages = {131-3}, abstract = {

We describe a data collection method that uses a single crystal to solve X-ray structures by native SAD (single-wavelength anomalous diffraction). We solved the structures of 11 real-life examples, including a human membrane protein, a protein-DNA complex and a 266-kDa multiprotein-ligand complex, using this method. The data collection strategy is suitable for routine structure determination and can be implemented at most macromolecular crystallography synchrotron beamlines.

}, keywords = {Animals, DNA-Binding Proteins, Humans, Membrane Proteins, Models, Molecular, Multiprotein Complexes, Protein Conformation, Software, Synchrotrons, X-Ray Diffraction}, issn = {1548-7105}, doi = {10.1038/nmeth.3211}, author = {Weinert, Tobias and Olieric, Vincent and Waltersperger, Sandro and Panepucci, Ezequiel and Chen, Lirong and Zhang, Hua and Zhou, Dayong and Rose, John and Ebihara, Akio and Kuramitsu, Seiki and Li, Dianfan and Howe, Nicole and Schnapp, Gisela and Pautsch, Alexander and Bargsten, Katja and Prota, Andrea E and Surana, Parag and Kottur, Jithesh and Nair, Deepak T and Basilico, Federica and Cecatiello, Valentina and Pasqualato, Sebastiano and Boland, Andreas and Weichenrieder, Oliver and Wang, Bi-Cheng and Steinmetz, Michel O and Caffrey, Martin and Wang, Meitian} } @article {878, title = {Formation of a CH-π contact in the core of native barstar during folding.}, journal = {J Phys Chem B}, volume = {119}, year = {2015}, month = {2015 Feb 19}, pages = {2928-32}, abstract = {

An important part of the protein folding process is the consolidation of the protein core through the formation of specific, directional contacts after the initial hydrophobic collapse. Here, we simultaneously monitor formation of core contacts and assembly of secondary structure through salt-induced folding by using resonance Raman spectroscopy. Unfolded barstar at pH 12 was refolded by gradual addition of sodium sulfate salt. Altered spectral characteristics of the Trp53 residue suggest that the core of the protein attains a CH-π interaction at a low concentration of the salt, with an increase in the packing density. Further increase in salt concentration produces a reduction in the solvent accessibility of the core. These data provide evidence that the core of the protein becomes rigid upon the addition of 0.6 M sodium sulfate. This is the first time that the formation of a CH-π interaction has been directly monitored during the folding of a protein.

}, issn = {1520-5207}, doi = {10.1021/jp512036p}, author = {Mil{\'a}n-Garc{\'e}s, Erix A and Thaore, Pallavi and Udgaonkar, Jayant B and Puranik, Mrinalini} } @article {1042, title = {Functional characterization of a transition metal ion transporter, OsZIP6 from rice (Oryza sativa L.).}, journal = {Plant Physiol Biochem}, volume = {97}, year = {2015}, month = {2015 Dec}, pages = {165-74}, abstract = {

Micronutrients are important for the growth and development of plants, which deploy families of transporters for their uptake and distribution. We have functionally characterized a novel transition metal ion transporter from rice, OsZIP6 (Oryza sativa zinc regulated transporter, iron regulated transporter-like protein 6). The transporter was found to be transcriptionally activated in shoot and root tissues in response to deficiency in Fe(2+), Zn(2+) and Mn(2+). OsZIP6 was expressed in Xenopus laevis oocytes, where currents were observed on addition of Co(2+), Fe(2+) and Cd(2+) but not Zn(2+), Mn(2+) and Ni(2+). This substrate range for OsZIP6, identified using two-electrode voltage clamp electrophysiology was confirmed by atomic absorption spectroscopy. Ion transport by OsZIP6 was found to be pH dependent and enhanced transport was observed at acidic pH. Radioisotope uptake suggested that Co(2+) competitively inhibits Fe(2+) uptake by OsZIP6. Identification and characterization of ZIP family members from crop plants will contribute to an understanding of nutrient mineral homeostasis in these plants.

}, issn = {1873-2690}, doi = {10.1016/j.plaphy.2015.10.005}, author = {P G, Kavitha and Kuruvilla, Sam and Mathew, M K} } @article {880, title = {Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Jan 7}, pages = {325-38}, abstract = {

Neurodevelopmental disorders arise from single or multiple gene defects. However, the way multiple loci interact to modify phenotypic outcomes remains poorly understood. Here, we studied phenotypes associated with mutations in the schizophrenia susceptibility gene dysbindin (dysb), in isolation or in combination with null alleles in the dysb network component Blos1. In humans, the Blos1 ortholog Bloc1s1 encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence in Drosophila neurons, and measured synaptic output and complex adaptive behavior in response to BLOC-1 perturbation. Homozygous loss-of-function alleles of dysb, Blos1, or compound heterozygotes of these alleles impaired neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval neuromuscular junction, and impaired olfactory habituation. This multiparameter assessment indicated that phenotypes were differentially sensitive to genetic dosages of loss-of-function BLOC-1 alleles. Our findings suggest that modification of a second genetic locus in a defined neurodevelopmental regulatory network does not follow a strict additive genetic inheritance, but rather, precise stoichiometry within the network determines phenotypic outcomes.

}, keywords = {Animals, Animals, Genetically Modified, Carrier Proteins, Drosophila, Drosophila Proteins, Dystrophin-Associated Proteins, Female, Gene Dosage, Nerve Net, Neuronal Plasticity, Schizophrenia, Synapses, Synaptic Transmission}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3542-14.2015}, author = {Mullin, Ariana P and Sadanandappa, Madhumala K and Ma, Wenpei and Dickman, Dion K and VijayRaghavan, Krishnaswamy and Ramaswami, Mani and Sanyal, Subhabrata and Faundez, Victor} } @article {161, title = {Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties.}, journal = {BMC Plant Biol}, volume = {15}, year = {2015}, month = {2015}, pages = {212}, abstract = {

BACKGROUND: Krishna Tulsi, a member of Lamiaceae family, is a herb well known for its spiritual, religious and medicinal importance in India. The common name of this plant is {\textquoteright}Tulsi{\textquoteright} (or {\textquoteright}Tulasi{\textquoteright} or {\textquoteright}Thulasi{\textquoteright}) and is considered sacred by Hindus. We present the draft genome of Ocimum tenuiflurum L (subtype Krishna Tulsi) in this report. The paired-end and mate-pair sequence libraries were generated for the whole genome sequenced with the Illumina Hiseq 1000, resulting in an assembled genome of 374~Mb, with a genome coverage of 61~\% (612~Mb estimated genome size). We have also studied transcriptomes (RNA-Seq) of two subtypes of O. tenuiflorum, Krishna and Rama Tulsi and report the relative expression of genes in both the varieties.

RESULTS: The pathways leading to the production of medicinally-important specialized metabolites have been studied in detail, in relation to similar pathways in Arabidopsis thaliana and other plants. Expression levels of anthocyanin biosynthesis-related genes in leaf samples of Krishna Tulsi were observed to be relatively high, explaining the purple colouration of Krishna Tulsi leaves. The expression of six important genes identified from genome data were validated by performing q-RT-PCR in different tissues of five different species, which shows the high extent of urosolic acid-producing genes in young leaves of the Rama subtype. In addition, the presence of eugenol and ursolic acid, implied as potential drugs in the cure of many diseases including cancer was confirmed using mass spectrometry.

CONCLUSIONS: The availability of the whole genome of O.tenuiflorum and our sequence analysis suggests that small amino acid changes at the functional sites of genes involved in metabolite synthesis pathways confer special medicinal properties to this herb.

}, issn = {1471-2229}, doi = {10.1186/s12870-015-0562-x}, author = {Upadhyay, Atul K and Chacko, Anita R and Gandhimathi, A and Ghosh, Pritha and Harini, K and Joseph, Agnel P and Joshi, Adwait G and Karpe, Snehal D and Kaushik, Swati and Kuravadi, Nagesh and Lingu, Chandana S and Mahita, J and Malarini, Ramya and Malhotra, Sony and Malini, Manoharan and Mathew, Oommen K and Mutt, Eshita and Naika, Mahantesha and Nitish, Sathyanarayanan and Pasha, Shaik Naseer and Raghavender, Upadhyayula S and Rajamani, Anantharamanan and Shilpa, S and Shingate, Prashant N and Singh, Heikham Russiachand and Sukhwal, Anshul and Sunitha, Margaret S and Sumathi, Manojkumar and Ramaswamy, S and Gowda, Malali and Sowdhamini, Ramanathan} } @article {905, title = {The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.}, journal = {Nucleic Acids Res}, volume = {43}, year = {2015}, month = {2015 Jan}, pages = {295-308}, abstract = {

The gene expression state of exponentially growing Escherichia coli cells is manifested by high expression of essential and growth-associated genes and low levels of stress-related and horizontally acquired genes. An important player in maintaining this homeostasis is the H-NS-StpA gene silencing system. A Δhns-stpA deletion mutant results in high expression of otherwise-silent horizontally acquired genes, many located in the terminus-half of the chromosome, and an indirect downregulation of many highly expressed genes. The Δhns-stpA double mutant displays slow growth. Using laboratory evolution we address the evolutionary strategies that E. coli would adopt to redress this gene expression imbalance. We show that two global gene regulatory mutations-(i) point mutations inactivating the stress-responsive sigma factor RpoS or σ38 and (ii) an amplification of \~{}40\% of the chromosome centred around the origin of replication-converge in partially reversing the global gene expression imbalance caused by Δhns-stpA. Transcriptome data of these mutants further show a three-way link amongst the global gene regulatory networks of H-NS and σ38, as well as chromosome architecture. Increasing gene expression around the terminus of replication results in a decrease in the expression of genes around the origin and vice versa; this appears to be a persistent phenomenon observed as an association across \~{}300 publicly-available gene expression data sets for E. coli. These global suppressor effects are transient and rapidly give way to more specific mutations, whose roles in reversing the growth defect of H-NS mutations remain to be understood.

}, keywords = {Chromosomes, Bacterial, Directed Molecular Evolution, DNA-Binding Proteins, DNA-Directed RNA Polymerases, Escherichia coli, Escherichia coli Proteins, Gene Deletion, Gene Expression Regulation, Bacterial, Gene Silencing, Genome, Bacterial, Molecular Chaperones, Sigma Factor, Stress, Physiological, Transcription, Genetic}, issn = {1362-4962}, doi = {10.1093/nar/gku1229}, author = {Srinivasan, Rajalakshmi and Scolari, Vittore Ferdinando and Lagomarsino, Marco Cosentino and Seshasayee, Aswin Sai Narain} } @article {875, title = {Higher speciation and lower extinction rates influence mammal diversity gradients in Asia.}, journal = {BMC Evol Biol}, volume = {15}, year = {2015}, month = {2015}, pages = {11}, abstract = {

BACKGROUND: Little is known about the patterns and correlates of mammal diversity gradients in Asia. In this study, we examine patterns of species distributions and phylogenetic diversity in Asia and investigate if the observed diversity patterns are associated with differences in diversification rates between the tropical and non-tropical regions. We used species distribution maps and phylogenetic trees to generate species and phylogenetic diversity measures for 1{\textdegree} {\texttimes} 1{\textdegree} cells across mainland Asia. We constructed lineage-through-time plots and estimated diversification shift-times to examine the temporal patterns of diversifications across orders. Finally, we tested if the observed gradients in Asia could be associated with geographical differences in diversification rates across the tropical and non-tropical biomes. We estimated speciation, extinction and dispersal rates across these two regions for mammals, both globally and for Asian mammals.

RESULTS: Our results demonstrate strong latitudinal and longitudinal gradients of species and phylogenetic diversity with Southeast Asia and the Himalayas showing highest diversity. Importantly, our results demonstrate that differences in diversification (speciation, extinction and dispersal) rates between the tropical and the non-tropical biomes influence the observed diversity gradients globally and in Asia. For the first time, we demonstrate that Asian tropics act as both cradles and museums of mammalian diversity.

CONCLUSIONS: Temporal and spatial variation in diversification rates across different lineages of mammals is an important correlate of species diversity gradients observed in Asia.

}, keywords = {Animals, Asia, Biodiversity, Genetic Speciation, Mammals, Phylogeny}, issn = {1471-2148}, doi = {10.1186/s12862-015-0289-1}, author = {Tamma, Krishnapriya and Ramakrishnan, Uma} } @article {863, title = {Homo-FRET imaging highlights the nanoscale organization of cell surface molecules.}, journal = {Methods Mol Biol}, volume = {1251}, year = {2015}, month = {2015}, pages = {151-73}, abstract = {

Several models have been proposed to understand the structure and organization of the plasma membrane in living cells. Predicated on equilibrium thermodynamic principles, the fluid-mosaic model of Singer and Nicholson and the model of lipid domains (or membrane rafts) are dominant models, which account for a fluid bilayer and functional lateral heterogeneity of membrane components, respectively. However, the constituents of the membrane and its composition are not maintained by equilibrium mechanisms. Indeed, the living cell membrane is a steady state of a number of active processes, namely, exocytosis, lipid synthesis and transbilayer flip-flop, and endocytosis. In this active milieu, many lipid constituents of the cell membrane exhibit a nanoscale organization that is also at odds with passive models based on chemical equilibrium. Here we provide a detailed description of microscopy and cell biological methods that have served to provide valuable information regarding the nature of nanoscale organization of lipid components in a living cell.

}, keywords = {Animals, Cell Membrane, CHO Cells, Cricetinae, Cricetulus, Fluorescence Polarization, Fluorescence Resonance Energy Transfer, Lipid Bilayers, Microscopy, Fluorescence, Models, Biological, Nanotechnology}, issn = {1940-6029}, doi = {10.1007/978-1-4939-2080-8_9}, author = {Saha, Suvrajit and Raghupathy, Riya and Mayor, Satyajit} } @article {1037, title = {An Interglomerular Circuit Gates Glomerular Output and Implements Gain Control in the Mouse Olfactory Bulb.}, journal = {Neuron}, volume = {87}, year = {2015}, month = {2015 Jul 1}, pages = {193-207}, abstract = {

Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration-dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness.

}, keywords = {Animals, Dopamine Plasma Membrane Transport Proteins, Dopaminergic Neurons, GABAergic Neurons, Mice, Neurons, Odors, Olfactory Bulb, Synaptic Transmission}, issn = {1097-4199}, doi = {10.1016/j.neuron.2015.06.019}, author = {Banerjee, Arkarup and Marbach, Fred and Anselmi, Francesca and Koh, Matthew S and Davis, Martin B and Garcia da Silva, Pedro and Delevich, Kristen and Oyibo, Hassana K and Gupta, Priyanka and Li, Bo and Albeanu, Dinu F} } @article {1001, title = {Islands within islands: two montane palaeo-endemic birds impacted by recent anthropogenic fragmentation.}, journal = {Mol Ecol}, volume = {24}, year = {2015}, month = {2015 Jul}, pages = {3572-84}, abstract = {

Anthropogenic habitat fragmentation of species that live in naturally patchy metapopulations such as mountaintops or sky islands experiences two levels of patchiness. Effects of such multilevel patchiness on species have rarely been examined. Metapopulation theory suggests that patchy habitats could have varied impacts on persistence, dependent on differential migration. It is not known whether montane endemic species, evolutionarily adapted to natural patchiness, are able to disperse between anthropogenic fragments at similar spatial scales as natural patches. We investigated historic and contemporary gene flow between natural and anthropogenic patches across the distribution range of a Western Ghats sky-island-endemic bird species complex. Data from 14 microsatellites for 218 individuals detected major genetic structuring by deep valleys, including one hitherto undescribed barrier. As expected, we found strong effects of historic genetic differentiation across natural patches, but not across anthropogenic fragments. Contrastingly, contemporary differentiation (D(PS)) was higher relative to historic differentiation (F(ST)) in anthropogenic fragments, despite the species{\textquoteright} ability to historically traverse shallow valleys. Simulations of recent isolation resulted in high D(PS)/F(ST) values, confirming recent isolation in Western Ghats anthropogenic fragments and also suggesting that this ratio can be used to identifying recent fragmentation in the context of historic connectedness. We suggest that in this landscape, in addition to natural patchiness affecting population connectivity, anthropogenic fragmentation additionally impacts connectivity, making anthropogenic fragments akin to islands within natural islands of montane habitat, a pattern that may be recovered in other sky-island systems.

}, keywords = {Animal Distribution, Animals, Computer Simulation, Conservation of Natural Resources, Ecosystem, Gene Flow, Genetic Variation, Genetics, Population, Geography, India, Microsatellite Repeats, Passeriformes, Phylogeography, Sequence Analysis, DNA}, issn = {1365-294X}, doi = {10.1111/mec.13266}, author = {Robin, V V and Gupta, Pooja and Thatte, Prachi and Ramakrishnan, Uma} } @article {884, title = {Key challenges for the creation and maintenance of specialist protein resources.}, journal = {Proteins}, volume = {83}, year = {2015}, month = {2015 Jun}, pages = {1005-13}, abstract = {

As the volume of data relating to proteins increases, researchers rely more and more on the analysis of published data, thus increasing the importance of good access to these data that vary from the supplemental material of individual articles, all the way to major reference databases with professional staff and long-term funding. Specialist protein resources fill an important middle ground, providing interactive web interfaces to their databases for a focused topic or family of proteins, using specialized approaches that are not feasible in the major reference databases. Many are labors of love, run by a single lab with little or no dedicated funding and there are many challenges to building and maintaining them. This perspective arose from a meeting of several specialist protein resources and major reference databases held at the Wellcome Trust Genome Campus (Cambridge, UK) on August 11 and 12, 2014. During this meeting some common key challenges involved in creating and maintaining such resources were discussed, along with various approaches to address them. In laying out these challenges, we aim to inform users about how these issues impact our resources and illustrate ways in which our working together could enhance their accuracy, currency, and overall value.

}, issn = {1097-0134}, doi = {10.1002/prot.24803}, author = {Holliday, Gemma L and Bairoch, Amos and Bagos, Pantelis G and Chatonnet, Arnaud and Craik, David J and Finn, Robert D and Henrissat, Bernard and Landsman, David and Manning, Gerard and Nagano, Nozomi and O{\textquoteright}Donovan, Claire and Pruitt, Kim D and Rawlings, Neil D and Saier, Milton and Sowdhamini, Ramanathan and Spedding, Michael and Srinivasan, Narayanaswamy and Vriend, Gert and Babbitt, Patricia C and Bateman, Alex} } @article {5218, title = {Landscape scale habitat suitability modelling of bats in the Western Ghats of India: Bats like something in their tea}, journal = {Biological Conservation}, volume = {191}, year = {2015}, month = {11/2015}, pages = {529{\textendash}536}, abstract = {

To conserve biodiversity it is imperative that we understand how different species respond to land use change, and determine the scales at which habitat changes affect species{\textquoteright} persistence. We used habitat suitability models (HSMs) at spatial scales from 100{\textendash}4000 m to address these concerns for bats in the Western Ghats of India, a biodiversity hotspot of global importance where the habitat requirements of bats are poorly understood. We used acoustic and capture data to build fine scale HSMs for ten species (Hesperoptenus tickelli, Miniopterus fuliginosus, Miniopterus pusillus, Myotis horsfieldii, Pipistrellus ceylonicus, Megaderma spasma, Hipposideros pomona, Rhinolophus beddomei, Rhinolophus indorouxii and Rhinolophus lepidus) in a tea-dominated landscape. Small (100{\textendash}500 m) scale habitat variables (e.g. percentage tea plantation cover) and distances to habitat features (e.g. distance to water) were the strongest predictors of bat occurrence, likely due to their high mobility, which enables them to exploit even small or isolated foraging areas. Most species showed a positive response to coffee plantations grown under native shade and to forest fragments, but a negative response to more heavily modified tea plantations. Two species were never recorded in tea plantations. This is the first study of bats in tea plantations globally, and the first ecological Old World bat study to combine acoustic and capture data. Our results suggest that although bats respond negatively to tea plantations, tea-dominated landscapes that also contain forest fragments and shade coffee can nevertheless support many bat species.

}, doi = {10.1016/j.biocon.2015.08.005}, author = {Claire F.R. Wordley and Mahesh Sankaran and Divya Mudappa and John D. Altringham} } @article {864, title = {Live cell plasma membranes do not exhibit a miscibility phase transition over a wide range of temperatures.}, journal = {J Phys Chem B}, volume = {119}, year = {2015}, month = {2015 Mar 26}, pages = {4450-9}, abstract = {

Lipid/cholesterol mixtures derived from cell membranes as well as their synthetic reconstitutions exhibit well-defined miscibility phase transitions and critical phenomena near physiological temperatures. This suggests that lipid/cholesterol-mediated phase separation plays a role in the organization of live cell membranes. However, macroscopic lipid-phase separation is not generally observed in cell membranes, and the degree to which properties of isolated lipid mixtures are preserved in the cell membrane remain unknown. A fundamental property of phase transitions is that the variation of tagged particle diffusion with temperature exhibits an abrupt change as the system passes through the transition, even when the two phases are distributed in a nanometer-scale emulsion. We support this using a variety of Monte Carlo and atomistic simulations on model lipid membrane systems. However, temperature-dependent fluorescence correlation spectroscopy of labeled lipids and membrane-anchored proteins in live cell membranes shows a consistently smooth increase in the diffusion coefficient as a function of temperature. We find no evidence of a discrete miscibility phase transition throughout a wide range of temperatures: 14-37 {\textdegree}C. This contrasts the behavior of giant plasma membrane vesicles (GPMVs) blebbed from the same cells, which do exhibit phase transitions and macroscopic phase separation. Fluorescence lifetime analysis of a DiI probe in both cases reveals a significant environmental difference between the live cell and the GPMV. Taken together, these data suggest the live cell membrane may avoid the miscibility phase transition inherent to its lipid constituents by actively regulating physical parameters, such as tension, in the membrane.

}, issn = {1520-5207}, doi = {10.1021/jp512839q}, author = {Lee, Il-Hyung and Saha, Suvrajit and Polley, Anirban and Huang, Hector and Mayor, Satyajit and Rao, Madan and Groves, Jay T} } @article {872, title = {Males and females gain differentially from sociality in a promiscuous fruit bat Cynopterus sphinx.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0122180}, abstract = {

Sociality emerges when the benefits of group living outweigh its costs. While both males and females are capable of strong social ties, the evolutionary drivers for sociality and the benefits accrued maybe different for each sex. In this study, we investigate the differential reproductive success benefits of group membership that males and females might obtain in the promiscuous fruit bat Cynopterus sphinx. Individuals of this species live in flexible social groups called colonies. These colonies are labile and there is high turnover of individuals. However, colony males sire more offspring within the colony suggesting that being part of a colony may result in reproductive benefits for males. This also raises the possibility that long-term loyalty towards the colony may confer additional advantage in terms of higher reproductive success. We used ten seasons of genetic parentage data to estimate reproductive success and relatedness of individuals in the colony. We used recapture data to identify long and short-term residents in the colony as well as to obtain rates of recapture for males and females. Our results reveal that males have a significantly higher chance of becoming long-term residents (than females), and these long-term resident males gain twice the reproductive success compared to short-term resident males. We also observed that long-term resident females are related to each other and also achieve higher reproductive success than short-term resident females. In contrast, long-term resident males do not differ from short-term resident males in their levels of relatedness. Our results re-iterate the benefits of sociality even in species that are promiscuous and socially labile and possible benefits of maintaining a colony.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0122180}, author = {Garg, Kritika M and Chattopadhyay, Balaji and Swami Doss, D P and Kumar, A K Vinoth and Kandula, Sripathi and Ramakrishnan, Uma} } @article {911, title = {Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca{\texttwosuperior}$^{+}$ signaling.}, journal = {Elife}, volume = {4}, year = {2015}, month = {2015}, abstract = {

The final identity of a differentiated neuron is determined by multiple signaling events, including activity dependent calcium transients. Non-canonical Frizzled2 (Fz2) signaling generates calcium transients that determine neuronal polarity, neuronal migration, and synapse assembly in the developing vertebrate brain. Here, we demonstrate a requirement for Fz2/Ca(2+) signaling in determining the final differentiated state of a set of central brain dopaminergic neurons in Drosophila, referred to as the protocerebral anterior medial (PAM) cluster. Knockdown or inhibition of Fz2/Ca(2+) signaling during maturation of the flight circuit in pupae reduces Tyrosine Hydroxylase (TH) expression in the PAM neurons and affects maintenance of flight. Thus, we demonstrate that Fz2/Ca(2+) transients during development serve as a pre-requisite for normal adult behavior. Our results support a neural mechanism where PAM neuron send projections to the α{\textquoteright} and β{\textquoteright} lobes of a higher brain centre, the mushroom body, and function in dopaminergic re-inforcement of flight.

}, issn = {2050-084X}, doi = {10.7554/eLife.07046}, author = {Agrawal, Tarjani and Hasan, Gaiti} } @article {1041, title = {Mechanistic Basis Of Peptide-Protein Interaction In AtPep1-PEPR1 Complex In Arabidopsis thaliana.}, journal = {Protein Pept Lett}, volume = {22}, year = {2015}, month = {2015}, pages = {618-27}, abstract = {

Peptide-mediated immunity against pathogens in plants can provide information on protein-peptide interactions and drug discovery in general. The molecular structure of AtPep1, a 23-amino acid signaling peptide isolated from Arabidopsis thaliana leaves and implicated in innate immunity, has evaded structural determination by biophysical methods. The details of molecular interaction of AtPep1 peptide with its receptor (PEPR1), a 170 kDa leucine-rich repeat (LRR) kinase is also unknown. We report a computational approach to the modeling AtPep1 by conformational sampling and its interaction with the receptor PEPR1. Molecular dynamics simulations were employed to sample and cluster energetically favorable conformations of AtPep1 and modeling of PEPR1 through homology. Docking of AtPep1 to PEPR1 and filtering of the biologically relevant poses were facilitated by the computational Ala-scanning mutations and binding energy analysis of the peptide-protein complex. This study provides the first independent in silico validation of the Structure-Activity- Relationship studies carried out on the AtPep1 and provides a molecular mechanism of the peptide-protein complex system.

}, issn = {1875-5305}, author = {Raghavender, Upadhyayula S and Sowdhamini, Ramanathan} } @article {891, title = {Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.}, journal = {J Biol Chem}, volume = {290}, year = {2015}, month = {2015 Mar 13}, pages = {7003-15}, abstract = {

The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca(2+) sensitivity of human β-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca(2+) activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca(2+) concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis.

}, keywords = {Actins, Adenosine Triphosphatases, Calcium, Cardiomyopathies, Humans, Models, Molecular, Myosins, Point Mutation, Protein Stability, Tropomyosin}, issn = {1083-351X}, doi = {10.1074/jbc.M114.596676}, author = {Gupte, Tejas M and Haque, Farah and Gangadharan, Binnu and Sunitha, Margaret S and Mukherjee, Souhrid and Anandhan, Swetha and Rani, Deepa Selvi and Mukundan, Namita and Jambekar, Amruta and Thangaraj, Kumarasamy and Sowdhamini, Ramanathan and Sommese, Ruth F and Nag, Suman and Spudich, James A and Mercer, John A} } @article {1012, title = {Mitochondrial Fragmentation Due to Inhibition of Fusion Increases Cyclin B through Mitochondrial Superoxide Radicals.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0126829}, abstract = {

During the cell cycle, mitochondria undergo regulated changes in morphology. Two particularly interesting events are first, mitochondrial hyperfusion during the G(1)-S transition and second, fragmentation during entry into mitosis. The mitochondria remain fragmented between late G(2)- and mitotic exit. This mitotic mitochondrial fragmentation constitutes a checkpoint in some cell types, of which little is known. We bypass the {\textquoteright}mitotic mitochondrial fragmentation{\textquoteright} checkpoint by inducing fragmented mitochondrial morphology and then measure the effect on cell cycle progression. Using Drosophila larval hemocytes, Drosophila S2R(+) cell and cells in the pouch region of wing imaginal disc of Drosophila larvae we show that inhibiting mitochondrial fusion, thereby increasing fragmentation, causes cellular hyperproliferation and an increase in mitotic index. However, mitochondrial fragmentation due to over-expression of the mitochondrial fission machinery does not cause these changes. Our experiments suggest that the inhibition of mitochondrial fusion increases superoxide radical content and leads to the upregulation of cyclin B that culminates in the observed changes in the cell cycle. We provide evidence for the importance of mitochondrial superoxide in this process. Our results provide an insight into the need for mitofusin-degradation during mitosis and also help in understanding the mechanism by which mitofusins may function as tumor suppressors.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0126829}, author = {Gupte, Tejas M} } @article {999, title = {Molecular Mechanism of the Misfolding and Oligomerization of the Prion Protein: Current Understanding and Its Implications.}, journal = {Biochemistry}, volume = {54}, year = {2015}, month = {2015 Jul 28}, pages = {4431-42}, abstract = {

Prion diseases, also known as transmissible spongiform encephalopathies, make up a group of fatal neurodegenerative disorders linked with the misfolding and aggregation of the prion protein (PrP). Although it is not yet understood how the misfolding of PrP induces neurodegeneration, it is widely accepted that the formation of misfolded prion protein (termed PrP(Sc)) is both the triggering event in the disease and the main component of the infectious agent responsible for disease transmission. Despite the clear involvement of PrP(Sc) in prion diseases, the exact composition of PrP(Sc) is not yet well-known. Recent studies show that misfolded oligomers of PrP could, however, be responsible for neurotoxicity and/or infectivity in the prion diseases. Hence, understanding the molecular mechanism of formation of the misfolded oligomers of PrP is critical for developing an understanding about the prion diseases and for developing anti-prion therapeutics. This review discusses recent advances in understanding the molecular mechanism of misfolded oligomer formation by PrP and its implications for the development of anti-prion therapeutics.

}, keywords = {Animals, Humans, Models, Molecular, Prion Diseases, Protein Folding, Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Secondary, PrPC Proteins, PrPSc Proteins}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5b00605}, author = {Singh, Jogender and Udgaonkar, Jayant B} } @article {1016, title = {Neighborhood matters: divergent patterns of stress-induced plasticity across the brain.}, journal = {Nat Neurosci}, volume = {18}, year = {2015}, month = {2015 Oct}, pages = {1364-75}, abstract = {

The fact that exposure to severe stress leads to the development of psychiatric disorders serves as the basic rationale for animal models of stress disorders. Clinical and neuroimaging studies have shown that three brain areas involved in learning and memory--the hippocampus, amygdala and prefrontal cortex--undergo distinct structural and functional changes in individuals with stress disorders. These findings from patient studies pose several challenges for animal models of stress disorders. For instance, why does stress impair cognitive function, yet enhance fear and anxiety? Can the same stressful experience elicit contrasting patterns of plasticity in the hippocampus, amygdala and prefrontal cortex? How does even a brief exposure to traumatic stress lead to long-lasting behavioral abnormalities? Thus, animal models of stress disorders must not only capture the unique spatio-temporal features of structural and functional alterations in these brain areas, but must also provide insights into the underlying neuronal plasticity mechanisms. This Review will address some of these key questions by describing findings from animal models on how stress-induced plasticity varies across different brain regions and thereby gives rise to the debilitating emotional and cognitive symptoms of stress-related psychiatric disorders.

}, keywords = {Animals, Brain, Humans, Neuronal Plasticity, Stress, Psychological}, issn = {1546-1726}, doi = {10.1038/nn.4115}, author = {Chattarji, Sumantra and Tomar, Anupratap and Suvrathan, Aparna and Ghosh, Supriya and Rahman, Mohammed Mostafizur} } @article {734, title = {Neural control of wing coordination in flies.}, journal = {Curr Biol}, volume = {25}, year = {2015}, month = {2015 Jan 5}, pages = {80-6}, abstract = {

At the onset of each flight bout in flies, neural circuits in the CNS must rapidly integrate multimodal sensory stimuli and synchronously engage hinges of the left and right wings for coordinated wing movements. Whereas anatomical and physiological investigations of flight have been conducted on larger flies, molecular genetic studies in Drosophila have helped identify neurons that mediate various levels of flight control. However, neurons that might mediate bilateral coordination of wing movements to precisely synchronize left and right wing engagement at flight onset and maintain their movement in perfect coordination at rapid frequencies during flight maneuvers remain largely unexplored. Wing coordination could be directly modulated via bilateral sensory inputs to motoneurons of steering muscles and/or through central interneurons. Using a Ca(2+)-activity-based GFP reporter, we identified three flight-activated central dopaminergic interneurons in the ventral ganglion, which connect to and activate motoneurons that innervate a pair of direct-steering flight muscles. The activation of these newly identified dopaminergic interneurons is context specific. Whereas bilateral wing engagement for flight requires these neurons, they do not control unilateral wing extension during courtship. Thus, independent central circuits function in the context of different natural behaviors to control the motor circuit for Drosophila wing movement.

}, keywords = {Animals, Central Nervous System, Dopaminergic Neurons, Drosophila, Flight, Animal, Genes, Reporter, Male, Synapses, Wings, Animal}, issn = {1879-0445}, doi = {10.1016/j.cub.2014.10.069}, author = {Sadaf, Sufia and Reddy, O Venkateswara and Sane, Sanjay P and Hasan, Gaiti} } @article {907, title = {Neuronal encoding of the switch from specific to generalized fear.}, journal = {Nat Neurosci}, volume = {18}, year = {2015}, month = {2015 Jan}, pages = {112-20}, abstract = {

Fear memories are crucial for survival. However, excessive generalization of such memories, characterized by a failure to discriminate dangerous from safe stimuli, is common in anxiety disorders. Neuronal encoding of the transition from cue-specific to generalized fear is poorly understood. We identified distinct neuronal populations in the lateral amygdala (LA) of rats that signaled generalized versus cue-specific associations and determined how their distributions switched during fear generalization. Notably, the same LA neurons that were cue specific before the behavioral shift to generalized fear lost their specificity afterwards, thereby tilting the balance of activity toward a greater proportion of generalizing neurons. Neuronal activity in the LA, but not the auditory cortex, was necessary for fear generalization. Furthermore, targeted activation of cAMP-PKA signaling in the LA increased neuronal excitability of LA neurons and led to generalized fear. These results provide a cellular basis in the amygdala for the alteration of emotional states from normal to pathological fear.

}, keywords = {Animals, Auditory Cortex, Conditioning, Operant, Cyclic AMP-Dependent Protein Kinases, Discrimination (Psychology), Fear, GABA Agonists, Generalization (Psychology), Male, Mental Recall, Neuronal Plasticity, Neurons, Rats, Rats, Sprague-Dawley, Signal Transduction}, issn = {1546-1726}, doi = {10.1038/nn.3888}, author = {Ghosh, Supriya and Chattarji, Sumantra} } @article {2211, title = {A new species of damselfly, Protosticta ponmudiensis (Odonata: Zygoptera: Platystictidae) from Ponmudi Hills in the Western Ghats of India}, journal = {Journal of Threatened Taxa}, volume = {7}, year = {2015}, pages = {7146-7151}, author = {Kiran, C. G. and Kalesh, S. and Kunte, Krushnamegh} } @article {2210, title = {A new species of Hypolycaena (Lepidoptera: Lycenidae) from Arunachal Pradesh, north-eastern India}, journal = {The Journal of Research on the Lepidoptera}, volume = {48}, year = {2015}, pages = {21-27}, author = {Kunte, Krushnamegh} } @article {5220, title = {Non-stationary and non-linear influence of ENSO and Indian Ocean Dipole on the variability of Indian monsoon rainfall and extreme rain events}, journal = {Climate Dynamics}, volume = {45}, year = {2015}, pages = {175-184.}, author = {Krishnaswamy, J. and Vaidyanathan, S. and Rajagopalan , B. and Bonell, M. and Sankaran, M. and Bhalla, R. S. and Badiger, S.} } @article {860, title = {Notch4 Signaling Confers Susceptibility to TRAIL-Induced Apoptosis in Breast Cancer Cells.}, journal = {J Cell Biochem}, volume = {116}, year = {2015}, month = {2015 Jul}, pages = {1371-80}, abstract = {

Notch signaling has been established as a key regulator of cell fate in development, differentiation, and homeostasis. In breast cancers, increased Notch1 and Notch4 activity have been implicated in tumor progression and, accumulation of the intracellular domain of Notch4 (ICN4), reported in basal breast cancer cells. While, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have demonstrated selectively in targeting tumor cells, the majority of primary tumors are resistant to TRAIL. This necessitates the identification of factors that might regulate TRAIL sensitivity. Here we investigate TRAIL sensitivity in tumor cells following the modulation of Notch (1 and 4) activity using siRNA-mediated depletions or ectopic expression of GFP-tagged constructs of the intracellular domains of Notch1 (ICN1) or Notch4 (ICN4). Our findings suggest that Notch4, but not Notch1 signaling, sensitizes breast tumor cells to TRAIL-induced apoptosis. ICN4-induced sensitization to TRAIL is characterized by CBF1-dependence. Apoptosis was mediated via caspase-8 activation and regulated by the Bcl-2 family pro-apoptotic proteins Bak and Bid. Finally, we present evidence that endogenous Notch4 activity regulates susceptibility to TRAIL in basal-like breast cancer cells but not in cell lines of luminal origin. These experiments reveal a hitherto unexplored Notch4-TRAIL signaling axis in breast cancer cells.

}, issn = {1097-4644}, doi = {10.1002/jcb.25094}, author = {Naik, Shambhavi and MacFarlane, Marion and Sarin, Apurva} } @article {901, title = {NrichD database: sequence databases enriched with computationally designed protein-like sequences aid in remote homology detection.}, journal = {Nucleic Acids Res}, volume = {43}, year = {2015}, month = {2015 Jan}, pages = {D300-5}, abstract = {

NrichD (http://proline.biochem.iisc.ernet.in/NRICHD/) is a database of computationally designed protein-like sequences, augmented into natural sequence databases that can perform hops in protein sequence space to assist in the detection of remote relationships. Establishing protein relationships in the absence of structural evidence or natural {\textquoteright}intermediately related sequences{\textquoteright} is a challenging task. Recently, we have demonstrated that the computational design of artificial intermediary sequences/linkers is an effective approach to fill naturally occurring voids in protein sequence space. Through a large-scale assessment we have demonstrated that such sequences can be plugged into commonly employed search databases to improve the performance of routinely used sequence search methods in detecting remote relationships. Since it is anticipated that such data sets will be employed to establish protein relationships, two databases that have already captured these relationships at the structural and functional domain level, namely, the SCOP database and the Pfam database, have been {\textquoteright}enriched{\textquoteright} with these artificial intermediary sequences. NrichD database currently contains 3,611,010 artificial sequences that have been generated between 27,882 pairs of families from 374 SCOP folds. The data sets are freely available for download. Additional features include the design of artificial sequences between any two protein families of interest to the user.

}, keywords = {Computational Biology, Databases, Protein, Internet, Molecular Sequence Annotation, Protein Structure, Tertiary, Sequence Analysis, Protein, Sequence Homology, Amino Acid}, issn = {1362-4962}, doi = {10.1093/nar/gku888}, author = {Mudgal, Richa and Sandhya, Sankaran and Kumar, Gayatri and Sowdhamini, Ramanathan and Chandra, Nagasuma R and Srinivasan, Narayanaswamy} } @article {857, title = {Olfactory bulb coding of odors, mixtures and sniffs is a linear sum of odor time profiles.}, journal = {Nat Neurosci}, volume = {18}, year = {2015}, month = {2015 Feb}, pages = {272-81}, abstract = {

The olfactory system receives intermittent and fluctuating inputs arising from dispersion of odor plumes and active sampling by the animal. Previous work has suggested that the olfactory transduction machinery and excitatory-inhibitory olfactory bulb circuitry generate nonlinear population trajectories of neuronal activity that differ across odorants. Here we show that individual mitral/tufted (M/T) cells sum inputs linearly across odors and time. By decoupling odor sampling from respiration in anesthetized rats, we show that M/T cell responses to arbitrary odor waveforms and mixtures are well described by odor-specific impulse responses convolved with the odorant{\textquoteright}s temporal profile. The same impulse responses convolved with the respiratory airflow predict the classical respiration-locked firing of olfactory bulb neurons and several other reported response properties of M/T cells. These results show that the olfactory bulb linearly processes fluctuating odor inputs, thereby simplifying downstream decoding of stimulus identity and temporal dynamics.

}, keywords = {Animals, Female, Models, Neurological, Neurons, Odors, Olfactory Bulb, Olfactory Perception, Olfactory Receptor Neurons, Rats, Rats, Wistar, Respiration, Time Factors}, issn = {1546-1726}, doi = {10.1038/nn.3913}, author = {Gupta, Priyanka and Albeanu, Dinu F and Bhalla, Upinder S} } @article {3536, title = {Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion.}, journal = {Mol Biol Cell}, volume = {26}, year = {2015}, month = {2015 Dec 15}, pages = {4700-17}, abstract = {

Hedgehog (Hh) is a secreted morphogen involved in both short- and long-range signaling necessary for tissue patterning during development. It is unclear how this dually lipidated protein is transported over a long range in the aqueous milieu of interstitial spaces. We previously showed that the long-range signaling of Hh requires its oligomerization. Here we show that Hh is secreted in the form of exovesicles. These are derived by the endocytic delivery of cell surface Hh to multivesicular bodies (MVBs) via an endosomal sorting complex required for transport (ECSRT)-dependent process. Perturbations of ESCRT proteins have a selective effect on long-range Hh signaling in Drosophila wing imaginal discs. Of importance, oligomerization-defective Hh is inefficiently incorporated into exovesicles due to its poor endocytic delivery to MVBs. These results provide evidence that nanoscale organization of Hh regulates the secretion of Hh on ESCRT-derived exovesicles, which in turn act as a vehicle for long-range signaling.

}, issn = {1939-4586}, doi = {10.1091/mbc.E15-09-0671}, author = {Parchure, Anup and Vyas, Neha and Ferguson, Charles and Parton, Robert G and Mayor, Satyajit} } @article {902, title = {Organelle morphogenesis by active membrane remodeling.}, journal = {Soft Matter}, volume = {11}, year = {2015}, month = {2015 Mar 28}, pages = {2387-93}, abstract = {

Intracellular organelles are subject to a steady flux of lipids and proteins through active, energy consuming transport processes. Active fission and fusion are promoted by GTPases, e.g., Arf-Coatamer and the Rab-Snare complexes, which both sense and generate local membrane curvature. Here we investigate, through Dynamical Triangulation Monte Carlo simulations, the role that these active processes play in determining the morphology and composition segregation in closed membranes. We find that the steady state shapes obtained as a result of such active processes, bear a striking resemblance to the ramified morphologies of organelles in vivo, pointing to the relevance of nonequilibrium fission-fusion in organelle morphogenesis.

}, keywords = {Intracellular Membranes, Membrane Fusion, Models, Biological, Models, Statistical, Monte Carlo Method, Organelles}, issn = {1744-6848}, doi = {10.1039/c4sm02311k}, author = {Ramakrishnan, N and Ipsen, John H and Rao, Madan and Kumar, P B Sunil} } @article {162, title = {Partially Unfolded Forms of the Prion Protein Populated under Misfolding-promoting Conditions: CHARACTERIZATION BY HYDROGEN EXCHANGE MASS SPECTROMETRY AND NMR.}, journal = {J Biol Chem}, volume = {290}, year = {2015}, month = {2015 Oct 16}, pages = {25227-40}, abstract = {

The susceptibility of the cellular prion protein (PrP(C)) to convert to an alternative misfolded conformation (PrP(Sc)), which is the key event in the pathogenesis of prion diseases, is indicative of a conformationally flexible native (N) state. In the present study, hydrogen-deuterium exchange (HDX) in conjunction with mass spectrometry and nuclear magnetic resonance spectroscopy were used for the structural and energetic characterization of the N state of the full-length mouse prion protein, moPrP(23-231), under conditions that favor misfolding. The kinetics of HDX of 34 backbone amide hydrogens in the N state were determined at pH 4. In contrast to the results of previous HDX studies on the human and Syrian hamster prion proteins at a higher pH, various segments of moPrP were found to undergo different extents of subglobal unfolding events at pH 4, a pH at which the protein is known to be primed to misfold to a β-rich conformation. No residual structure around the disulfide bond was observed for the unfolded state at pH 4. The N state of the prion protein was observed to be at equilibrium with at least two partially unfolded forms (PUFs). These PUFs, which are accessed by stochastic fluctuations of the N state, have altered surface area exposure relative to the N state. One of these PUFs resembles a conformation previously implicated to be an initial intermediate in the conversion of monomeric protein into misfolded oligomer at pH 4.

}, issn = {1083-351X}, doi = {10.1074/jbc.M115.677575}, author = {Moulick, Roumita and Das, Ranabir and Udgaonkar, Jayant B} } @article {5219, title = {Perceptions of priority issues in the conservation of biodiversity and ecosystems in India}, journal = {Biological Conservation }, volume = {187}, year = {2015}, month = {2015}, pages = {201-211}, author = {Varma, V. and Ratnam, J. and Viswanathan, V. and Osuri, A. M. and Biesmeijer, J. C. and Madhusudan, M. D. and Sankaran, M.} } @article {912, title = {A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells.}, journal = {Nat Nanotechnol}, volume = {10}, year = {2015}, month = {2015 Jul}, pages = {645-51}, abstract = {

The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5-130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b.

}, issn = {1748-3395}, doi = {10.1038/nnano.2015.130}, author = {Saha, Sonali and Prakash, Ved and Halder, Saheli and Chakraborty, Kasturi and Krishnan, Yamuna} } @article {885, title = {Phosphoinositide signalling in Drosophila.}, journal = {Biochim Biophys Acta}, volume = {1851}, year = {2015}, month = {2015 Jun}, pages = {770-84}, abstract = {

Phosphoinositides (PtdInsPs) are lipids that mediate a range of conserved cellular processes in eukaryotes. These include the transduction of ligand binding to cell surface receptors, vesicular transport and cytoskeletal function. The nature and functions of PtdInsPs were initially elucidated through biochemical experiments in mammalian cells. However, over the years, genetic and cell biological analysis in a range of model organisms including S. cerevisiae, D. melanogaster and C. elegans have contributed to an understanding of the involvement of PtdInsPs in these cellular events. The fruit fly Drosophila is an excellent genetic model for the analysis of cell and developmental biology as well as physiological processes, particularly analysis of the complex relationship between the cell types of a metazoan in mediating animal physiology. PtdInsP signalling pathways are underpinned by enzymes that synthesise and degrade these molecules and also by proteins that bind to these lipids in cells. In this review we provide an overview of the current understanding of PtdInsP signalling in Drosophila. We provide a comparative genomic analysis of the PtdInsP signalling toolkit between Drosophila and mammalian systems. We also review some areas of cell and developmental biology where analysis in Drosophila might provide insights into the role of this lipid-signalling pathway in metazoan biology. This article is part of a Special Issue entitled Phosphoinositides.

}, keywords = {Animals, CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Isoenzymes, Phosphatidylinositol 4,5-Diphosphate, Phosphoinositide Phospholipase C, Phospholipid Transfer Proteins, Receptors, Cell Surface, Signal Transduction, Species Specificity, Substrate Specificity}, issn = {0006-3002}, doi = {10.1016/j.bbalip.2014.10.010}, author = {Balakrishnan, Sruthi S and Basu, Urbashi and Raghu, Padinjat} } @article {1007, title = {Physical principles of membrane remodelling during cell mechanoadaptation.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {7292}, abstract = {

Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope--the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.

}, issn = {2041-1723}, doi = {10.1038/ncomms8292}, author = {Kosmalska, Anita Joanna and Casares, Laura and Elosegui-Artola, Alberto and Thottacherry, Joseph Jose and Moreno-Vicente, Roberto and Gonz{\'a}lez-Tarrag{\'o}, V{\'\i}ctor and del Pozo, Miguel {\'A}ngel and Mayor, Satyajit and Arroyo, Marino and Navajas, Daniel and Trepat, Xavier and Gauthier, Nils C and Roca-Cusachs, Pere} } @article {998, title = {Plant species{\textquoteright} origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {7710}, abstract = {

Exotic species dominate many communities; however the functional significance of species{\textquoteright} biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

}, issn = {2041-1723}, doi = {10.1038/ncomms8710}, author = {Seabloom, Eric W and Borer, Elizabeth T and Buckley, Yvonne M and Cleland, Elsa E and Davies, Kendi F and Firn, Jennifer and Harpole, W Stanley and Hautier, Yann and Lind, Eric M and MacDougall, Andrew S and Orrock, John L and Prober, Suzanne M and Adler, Peter B and Anderson, T Michael and Bakker, Jonathan D and Biederman, Lori A and Blumenthal, Dana M and Brown, Cynthia S and Brudvig, Lars A and Cadotte, Marc and Chu, Chengjin and Cottingham, Kathryn L and Crawley, Michael J and Damschen, Ellen I and Dantonio, Carla M and DeCrappeo, Nicole M and Du, Guozhen and Fay, Philip A and Frater, Paul and Gruner, Daniel S and Hagenah, Nicole and Hector, Andy and Hillebrand, Helmut and Hofmockel, Kirsten S and Humphries, Hope C and Jin, Virginia L and Kay, Adam and Kirkman, Kevin P and Klein, Julia A and Knops, Johannes M H and La Pierre, Kimberly J and Ladwig, Laura and Lambrinos, John G and Li, Qi and Li, Wei and Marushia, Robin and McCulley, Rebecca L and Melbourne, Brett A and Mitchell, Charles E and Moore, Joslin L and Morgan, John and Mortensen, Brent and O{\textquoteright}Halloran, Lydia R and Pyke, David A and Risch, Anita C and Sankaran, Mahesh and Schuetz, Martin and Simonsen, Anna and Smith, Melinda D and Stevens, Carly J and Sullivan, Lauren and Wolkovich, Elizabeth and Wragg, Peter D and Wright, Justin and Yang, Louie} } @article {1032, title = {PPCheck: A Webserver for the Quantitative Analysis of Protein-Protein Interfaces and Prediction of Residue Hotspots.}, journal = {Bioinform Biol Insights}, volume = {9}, year = {2015}, month = {2015}, pages = {141-51}, abstract = {

BACKGROUND: Modeling protein-protein interactions (PPIs) using docking algorithms is useful for understanding biomolecular interactions and mechanisms. Typically, a docking algorithm generates a large number of docking poses, and it is often challenging to select the best native-like pose. A further challenge is to recognize key residues, termed as hotspots, at protein-protein interfaces, which contribute more in stabilizing a protein-protein interface.

RESULTS: We had earlier developed a computer algorithm, called PPCheck, which ascribes pseudoenergies to measure the strength of PPIs. Native-like poses could be successfully identified in 27 out of 30 test cases, when applied on a separate set of decoys that were generated using FRODOCK. PPCheck, along with conservation and accessibility scores, was able to differentiate {\textquoteright}native-like and non-native-like poses from 1883 decoys of Critical Assessment of Prediction of Interactions (CAPRI) targets with an accuracy of 60\%. PPCheck was trained on a 10-fold mixed dataset and tested on a 10-fold mixed test set for hotspot prediction. We obtain an accuracy of 72\%, which is in par with other methods, and a sensitivity of 59\%, which is better than most existing methods available for hotspot prediction that uses similar datasets. Other relevant tests suggest that PPCheck can also be reliably used to identify conserved residues in a protein and to perform computational alanine scanning.

CONCLUSIONS: PPCheck webserver can be successfully used to differentiate native-like and non-native-like docking poses, as generated by docking algorithms. The webserver can also be a convenient platform for calculating residue conservation, for performing computational alanine scanning, and for predicting protein-protein interface hotspots. While PPCheck can differentiate the generated decoys into native-like and non-native-like decoys with a fairly good accuracy, the results improve dramatically when features like conservation and accessibility are included. The method can be successfully used in ranking/scoring the decoys, as obtained from docking algorithms.

}, issn = {1177-9322}, doi = {10.4137/BBI.S25928}, author = {Sukhwal, Anshul and Sowdhamini, Ramanathan} } @article {1622, title = {Prey from the eyes of predators: Color discriminability of aposematic and mimetic butterflies from an avian visual perspective.}, journal = {Evolution}, volume = {69}, year = {2015}, month = {2015 Nov}, pages = {2985-94}, abstract = {

Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators{\textquoteright} perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner.

}, issn = {1558-5646}, doi = {10.1111/evo.12800}, author = {Su, Shiyu and Lim, Matthew and Kunte, Krushnamegh} } @article {1039, title = {Pre-yield non-affine fluctuations and a hidden critical point in strained crystals.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {10644}, abstract = {

A crystalline solid exhibits thermally induced localised non-affine droplets in the absence of external stress. Here we show that upon an imposed shear, the size of these droplets grow until they percolate at a critical strain, well below the value at which the solid begins to yield. This critical point does not manifest in most thermodynamic or mechanical properties, but is hidden and reveals itself in the onset of inhomogeneities in elastic moduli, marked changes in the appearance and local properties of non-affine droplets and a sudden enhancement in defect pair concentration. Slow relaxation of stress and an-elasticity appear as observable dynamical consequences of this hidden criticality. Our results may be directly verified in colloidal crystals with video microscopy techniques but are expected to have more general validity.

}, issn = {2045-2322}, doi = {10.1038/srep10644}, author = {Das, Tamoghna and Ganguly, Saswati and Sengupta, Surajit and Rao, Madan} } @article {887, title = {Protein unfolding rates correlate as strongly as folding rates with native structure.}, journal = {Protein Sci}, volume = {24}, year = {2015}, month = {2015 Apr}, pages = {580-7}, abstract = {

Although the folding rates of proteins have been studied extensively, both experimentally and theoretically, and many native state topological parameters have been proposed to correlate with or predict these rates, unfolding rates have received much less attention. Moreover, unfolding rates have generally been thought either to not relate to native topology in the same manner as folding rates, perhaps depending on different topological parameters, or to be more difficult to predict. Using a dataset of 108 proteins including two-state and multistate folders, we find that both unfolding and folding rates correlate strongly, and comparably well, with well-established measures of native topology, the absolute contact order and the long range order, with correlation coefficient values of 0.75 or higher. In addition, compared to folding rates, the absolute values of unfolding rates vary more strongly with native topology, have a larger range of values, and correlate better with thermodynamic stability. Similar trends are observed for subsets of different protein structural classes. Taken together, these results suggest that choosing a scaffold for protein engineering may require a compromise between a simple topology that will fold sufficiently quickly but also unfold quickly, and a complex topology that will unfold slowly and hence have kinetic stability, but fold slowly. These observations, together with the established role of kinetic stability in determining resistance to thermal and chemical denaturation as well as proteases, have important implications for understanding fundamental aspects of protein unfolding and folding and for protein engineering and design.

}, issn = {1469-896X}, doi = {10.1002/pro.2606}, author = {Broom, Aron and Gosavi, Shachi and Meiering, Elizabeth M} } @article {894, title = {Quaternary climate change and social behavior shaped the genetic differentiation of an endangered montane primate from the southern edge of the Tibetan Plateau.}, journal = {Am J Primatol}, volume = {77}, year = {2015}, month = {2015 Mar}, pages = {271-84}, abstract = {

Multiple factors, including climate change, dispersal barriers, and social behavior influence the genetic structure of natural populations. While the effects of extrinsic factors such as historical climatic change and habitat topography have been well studied, mostly in temperate habitats, the simultaneous effects of intrinsic factors such as social behavior on genetic structure have rarely been explored. Such simultaneous effect, however, may particularly be common in social mammals such as many primates. Consequently, we studied the population structure of a rare and endangered social primate, the Arunachal macaque Macaca munzala, endemic to the northeastern Indian state of Arunachal Pradesh, located on the subtropical southern edge of the Tibetan Plateau and forming part of the Eastern Himalayan biodiversity hotspot. We studied a 534 bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci in individuals from three populations, Tawang, Upper Subansiri, and West Siang. The mtDNA data revealed three major divergence events: that between the Arunachal and bonnet macaques (ca. 1.61 mya), the founding of the West Siang population and the ancestral population of the present-day bonnet macaques (ca. 1.32 mya), and the divergence between the Tawang and Upper Subansiri populations (ca. 0.80 mya) that coincided with the major glacial events in the region. Comparing mitochondrial DNA with autosomal microsatellites, we also found evidence for female philopatry and male-driven long-distance gene flow. Arunachal macaques thus appear to be characterized by groups of philopatric females separated by geographical barriers and harsh climate but with dispersing males exerting a homogenizing effect on the nuclear gene pool. Given that severe population differentiation is of major concern in species conservation, we suggest that our study populations represent significant conservation units of this rare, endangered primate but, more importantly, emphasize the complex interplay of extrinsic and intrinsic factors in shaping the population structure of a social mammalian species.

}, keywords = {Animals, Behavior, Animal, Climate Change, DNA, Mitochondrial, Ecosystem, Evolution, Molecular, Female, Gene Flow, Genetics, Population, India, Macaca, Male, Microsatellite Repeats, Phylogeography, Population Dynamics, Sequence Analysis, DNA, Social Behavior}, issn = {1098-2345}, doi = {10.1002/ajp.22343}, author = {Chakraborty, Debapriyo and Ramakrishnan, Uma and Sinha, Anindya} } @article {996, title = {RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction.}, journal = {J Cell Sci}, volume = {128}, year = {2015}, month = {2015 Sep 1}, pages = {3330-44}, abstract = {

Many membrane receptors activate phospholipase C (PLC) during signalling, triggering changes in the levels of several plasma membrane lipids including phosphatidylinositol (PtdIns), phosphatidic acid (PtdOH) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. It is widely believed that exchange of lipids between the plasma membrane and endoplasmic reticulum (ER) is required to restore lipid homeostasis during PLC signalling, yet the mechanism remains unresolved. RDGBα (hereafter RDGB) is a multi-domain protein with a PtdIns transfer protein (PITP) domain (RDGB-PITPd). We find that, in vitro, the RDGB-PITPd binds and transfers both PtdOH and PtdIns. In Drosophila photoreceptors, which experience high rates of PLC activity, RDGB function is essential for phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for normal phototransduction; however, this property is insufficient to explain the in vivo function because another Drosophila PITP (encoded by vib) that also binds PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants, PtdIns(4,5)P2 resynthesis at the plasma membrane following PLC activation is delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns and PtdOH, key lipid intermediates during G-protein-coupled PtdIns(4,5)P2 turnover.

}, issn = {1477-9137}, doi = {10.1242/jcs.173476}, author = {Yadav, Shweta and Garner, Kathryn and Georgiev, Plamen and Li, Michelle and Gomez-Espinosa, Evelyn and Panda, Aniruddha and Mathre, Swarna and Okkenhaug, Hanneke and Cockcroft, Shamshad and Raghu, Padinjat} } @article {1006, title = {Restriction modification systems as engines of diversity.}, journal = {Front Microbiol}, volume = {6}, year = {2015}, month = {2015}, pages = {528}, abstract = {

Restriction modification (RM) systems provide protection against a broad spectrum of phages. However, the likelihood of a phage permanently bypassing this can be as high as 0.1 per infection (Korona et al., 1993) which makes for a relatively weak defense. Here we argue that, apart from providing such transient defenses, RM systems can facilitate long-term coexistence of many bacterial strains. We show that this diversity can be as large as the burst size of the phage but no larger-a curious correspondence between a number at the level of species and another number at the level of individuals. Such a highly diverse and stably coexisting ecosystem is robust to substantial variation in both bacterial growth rates and strength of their RM systems, which might be one reason why quite weak RM systems exist in the wild.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2015.00528}, author = {Sneppen, Kim and Semsey, Szabolcs and Seshasayee, Aswin S N and Krishna, Sandeep} } @article {1027, title = {Rise of the Helix from a Collapsed Globule during the Folding of Monellin.}, journal = {Biochemistry}, volume = {54}, year = {2015}, month = {2015 Sep 1}, pages = {5356-65}, abstract = {

Early kinetic intermediates observed during the folding of many proteins are invariably compact and appear to possess some secondary structure. Consequently, it has been difficult to understand whether compaction drives secondary structure formation or secondary structure formation facilitates compaction during folding. In this study of the folding of single-chain monellin, it is shown that a kinetic molten globule (MG) is populated at 2 ms of folding. Far-UV circular dichroism (CD) measurements show that the kinetic MG is devoid of any helical structure even under the most stabilizing folding conditions. Multisite fluorescence resonance energy transfer (FRET) measurements show that the kinetic MG is compact with different segments having contracted to different extents. It is shown that the sequence segment that goes on to form the sole helix in the native protein is fully collapsed in the kinetic MG. This segment expands to accommodate the helix as the kinetic MG folds further to the native state, while other segments of the protein contract. Helix formation starting from the kinetic MG is shown to occur in multiple kinetic steps, whether measured by far-UV CD or by FRET.

}, keywords = {Amino Acid Substitution, Circular Dichroism, Cysteine, Fluorescence Resonance Energy Transfer, Hydrophobic and Hydrophilic Interactions, Kinetics, Models, Molecular, Mutagenesis, Site-Directed, Plant Proteins, Protein Conformation, Protein Folding, Protein Stability, Protein Structure, Secondary, Spectrometry, Fluorescence}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5b00730}, author = {Goluguri, Rama Reddy and Udgaonkar, Jayant B} } @article {1199, title = {Robust and Rapid Air-Borne Odor Tracking without Casting(1,2,3).}, journal = {eNeuro}, volume = {2}, year = {2015}, month = {2015 Nov-Dec}, abstract = {

Casting behavior (zigzagging across an odor stream) is common in air/liquid-borne odor tracking in open fields; however, terrestrial odor localization often involves path selection in a familiar environment. To study this, we trained rats to run toward an odor source in a multi-choice olfactory arena with near-laminar airflow. We find that rather than casting, rats run directly toward an odor port, and if this is incorrect, they serially sample other sources. This behavior is consistent and accurate in the presence of perturbations, such as novel odors, background odor, unilateral nostril stitching, and turbulence. We developed a model that predicts that this run-and-scan tracking of air-borne odors is faster than casting, provided there are a small number of targets at known locations. Thus, the combination of best-guess target selection with fallback serial sampling provides a rapid and robust strategy for finding odor sources in familiar surroundings.

}, issn = {2373-2822}, doi = {10.1523/ENEURO.0102-15.2015}, author = {Bhattacharyya, Urvashi and Singh Bhalla, Upinder} } @article {1034, title = {The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {13910}, abstract = {

Oscillators and switches are important elements of regulation in biological systems. These are composed of coupling negative feedback loops, which cause oscillations when delayed, and positive feedback loops, which lead to memory formation. Here, we examine the behavior of a coupled feedback system, the Negative Autoregulated Frustrated bistability motif (NAF). This motif is a combination of two previously explored motifs, the frustrated bistability motif (FBM) and the negative auto regulation motif (NAR), which both can produce oscillations. The NAF motif was previously suggested to govern long term memory formation in animals, and was used as a synthetic oscillator in bacteria. We build a mathematical model to analyze the dynamics of the NAF motif. We show analytically that the NAF motif requires an asymmetry in the strengths of activation and repression links in order to produce oscillations. We show that the effect of time delays in eukaryotic cells, originating from mRNA export and protein import, are negligible in this system. Based on the reported protein and mRNA half-lives in eukaryotic cells, we find that even though the NAF motif possesses the ability for oscillations, it mostly promotes constant protein expression at the biologically relevant parameter regimes.

}, issn = {2045-2322}, doi = {10.1038/srep13910}, author = {Moss Bendtsen, Kristian and Jensen, Mogens H and Krishna, Sandeep and Semsey, Szabolcs} } @article {882, title = {Salt-induced remodeling of spatially restricted clathrin-independent endocytic pathways in Arabidopsis root.}, journal = {Plant Cell}, volume = {27}, year = {2015}, month = {2015 Apr}, pages = {1297-315}, abstract = {

Endocytosis is a ubiquitous cellular process that is characterized well in animal cells in culture but poorly across intact, functioning tissue. Here, we analyze endocytosis throughout the Arabidopsis thaliana root using three classes of probes: a lipophilic dye, tagged transmembrane proteins, and a lipid-anchored protein. We observe a stratified distribution of endocytic processes. A clathrin-dependent endocytic pathway that internalizes transmembrane proteins functions in all cell layers, while a sterol-dependent, clathrin-independent pathway that takes up lipid and lipid-anchored proteins but not transmembrane proteins is restricted to the epidermal layer. Saline stress induces a third pathway that is clathrin-independent, nondiscriminatory in its choice of cargo, and operates across all layers of the root. Concomitantly, small acidic compartments in inner cell layers expand to form larger vacuole-like structures. Plants lacking function of the Rab-GEF (guanine nucleotide exchange factor) VPS9a (vacuolar protein sorting 9A) neither induce the third endocytic pathway nor expand the vacuolar system in response to salt stress. The plants are also hypersensitive to salt. Thus, saline stress reconfigures clathrin-independent endocytosis and remodels endomembrane systems, forming large vacuoles in the inner cell layers, both processes correlated by the requirement of VPS9a activity.

}, keywords = {Arabidopsis, Biological Transport, Clathrin, Endocytosis, Plant Roots, Signal Transduction, Sodium Chloride}, issn = {1532-298X}, doi = {10.1105/tpc.15.00154}, author = {Baral, Anirban and Irani, Niloufer G and Fujimoto, Masaru and Nakano, Akihiko and Mayor, Satyajit and Mathew, M K} } @article {3538, title = {Second messenger - Sensing riboswitches in bacteria.}, journal = {Semin Cell Dev Biol}, volume = {47-48}, year = {2015}, month = {2015 Dec}, pages = {3-8}, abstract = {

Signal sensing in bacteria has traditionally been attributed to protein-based factors. It is however becoming increasingly clear that bacteria also exploit RNAs to serve this role. This review discusses how key developmental processes in bacteria, such as community formation, choice of a sessile versus motile lifestyle, or vegetative growth versus dormant spore formation may be governed by signal sensing RNAs. The signaling molecules that affect these processes, the RNAs that sense these molecules and the underlying molecular basis for specific signal-response are discussed here.

}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2015.10.019}, author = {Ramesh, Arati} } @article {3537, title = {Sequence Analysis and Evolutionary Studies of Reelin Proteins.}, journal = {Bioinform Biol Insights}, volume = {9}, year = {2015}, month = {2015}, pages = {187-93}, abstract = {

The reelin gene is conserved across many vertebrate species, including humans. The protein product of this gene plays several important roles in early brain development and regulation of neural network plasticity of a matured brain structure. With an extended structure of 3461 amino acid sequences, consisting of eight reelin repeats, the human reelin sequence stands out as an exceptional model for evolutionary studies. In this study, sequence analysis of the human reelin and its homologues and reelin sequences from 104 other species is described in detail. Interesting sequence conservation patterns of individual repeats have been highlighted. Sequence phylogeny of the reelin sequences indicates a pattern similar to the evolution of the species, thereby serving as a highly conserved family for evolutionary purposes. Multiple sequence alignment of different reelin domain repeats, derived from homologues, suggests specific functions for individual repeats and high sequence conservation across reelin repeats from different organisms, albeit with few unusual domain architectures. A three-dimensional structural model of the full-length human reelin is now available that provides clues on residues at the dimer interface.

}, issn = {1177-9322}, doi = {10.4137/BBI.S26530}, author = {Manoharan, Malini and Muhammad, Sayyed Auwn and Sowdhamini, Ramanathan} } @article {1002, title = {SInCRe-structural interactome computational resource for Mycobacterium tuberculosis.}, journal = {Database (Oxford)}, volume = {2015}, year = {2015}, month = {2015}, pages = {bav060}, abstract = {

We have developed an integrated database for Mycobacterium tuberculosis H37Rv (Mtb) that collates information on protein sequences, domain assignments, functional annotation and 3D structural information along with protein-protein and protein-small molecule interactions. SInCRe (Structural Interactome Computational Resource) is developed out of CamBan (Cambridge and Bangalore) collaboration. The motivation for development of this database is to provide an integrated platform to allow easily access and interpretation of data and results obtained by all the groups in CamBan in the field of Mtb informatics. In-house algorithms and databases developed independently by various academic groups in CamBan are used to generate Mtb-specific datasets and are integrated in this database to provide a structural dimension to studies on tuberculosis. The SInCRe database readily provides information on identification of functional domains, genome-scale modelling of structures of Mtb proteins and characterization of the small-molecule binding sites within Mtb. The resource also provides structure-based function annotation, information on small-molecule binders including FDA (Food and Drug Administration)-approved drugs, protein-protein interactions (PPIs) and natural compounds that bind to pathogen proteins potentially and result in weakening or elimination of host-pathogen protein-protein interactions. Together they provide prerequisites for identification of off-target binding.

}, issn = {1758-0463}, doi = {10.1093/database/bav060}, author = {Metri, Rahul and Hariharaputran, Sridhar and Ramakrishnan, Gayatri and Anand, Praveen and Raghavender, Upadhyayula S and Ochoa-Monta{\~n}o, Bernardo and Higueruelo, Alicia P and Sowdhamini, Ramanathan and Chandra, Nagasuma R and Blundell, Tom L and Srinivasan, Narayanaswamy} } @article {1011, title = {Sloppiness in spontaneously active neuronal networks.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Jun 3}, pages = {8480-92}, abstract = {

Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function.

}, keywords = {Action Potentials, Animals, Brain, Cells, Cultured, Electric Stimulation, Embryo, Mammalian, Entropy, Models, Neurological, Nerve Net, Neural Pathways, Neurons, Rats, Synapses, Visual Cortex}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4421-14.2015}, author = {Panas, Dagmara and Amin, Hayder and Maccione, Alessandro and Muthmann, Oliver and van Rossum, Mark and Berdondini, Luca and Hennig, Matthias H} } @article {1200, title = {Spike Detection for Large Neural Populations Using High Density Multielectrode Arrays.}, journal = {Front Neuroinform}, volume = {9}, year = {2015}, month = {2015}, pages = {28}, abstract = {

An emerging generation of high-density microelectrode arrays (MEAs) is now capable of recording spiking activity simultaneously from thousands of neurons with closely spaced electrodes. Reliable spike detection and analysis in such recordings is challenging due to the large amount of raw data and the dense sampling of spikes with closely spaced electrodes. Here, we present a highly efficient, online capable spike detection algorithm, and an offline method with improved detection rates, which enables estimation of spatial event locations at a resolution higher than that provided by the array by combining information from multiple electrodes. Data acquired with a 4096 channel MEA from neuronal cultures and the neonatal retina, as well as synthetic data, was used to test and validate these methods. We demonstrate that these algorithms outperform conventional methods due to a better noise estimate and an improved signal-to-noise ratio (SNR) through combining information from multiple electrodes. Finally, we present a new approach for analyzing population activity based on the characterization of the spatio-temporal event profile, which does not require the isolation of single units. Overall, we show how the improved spatial resolution provided by high density, large scale MEAs can be reliably exploited to characterize activity from large neural populations and brain circuits.

}, issn = {1662-5196}, doi = {10.3389/fninf.2015.00028}, author = {Muthmann, Jens-Oliver and Amin, Hayder and Sernagor, Evelyne and Maccione, Alessandro and Panas, Dagmara and Berdondini, Luca and Upinder S Bhalla and Hennig, Matthias H} } @article {1033, title = {Store-Operated Calcium Entry through Orai Is Required for Transcriptional Maturation of the Flight Circuit in Drosophila.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Oct 7}, pages = {13784-99}, abstract = {

UNLABELLED: Store operated calcium entry (SOCE) is thought to primarily regulate calcium homeostasis in neurons. Subsequent to identification of Orai as the SOCE channel in nonexcitable cells, investigation of Orai function in neurons demonstrated a requirement for SOCE in Drosophila flight. Here, by analysis of an Orai mutant and by controlled expression of a dominant-negative Drosophila Orai transgene, we show that Orai-mediated SOCE is required in dopaminergic interneurons of the flight circuit during pupal development. Expression of dominant-negative Orai in dopaminergic neurons of pupae abolished flight. The loss of Orai-mediated SOCE alters transcriptional regulation of dopaminergic neurons, leading to downregulation of the enzyme tyrosine hydroxylase, which is essential for dopamine synthesis, and the dopamine transporter, which is required for dopamine uptake after synaptic release. These studies suggest that modulation of SOCE could serve as a novel mechanism for restoring dopamine levels in dopaminergic neurons.

SIGNIFICANCE STATEMENT: The specificity of an animal{\textquoteright}s response to an environmental stimulus is determined in part by the release of neurotransmitters, which are sensed by responding neurons through cognate receptors on their surface. One way by which neurons respond is through release of calcium from intracellular stores followed by store refilling from extracellular calcium sources. This mechanism is called store-operated calcium entry (SOCE). The function of SOCE in neurons has been debated. Here we describe a new function for SOCE in the regulation of neurotransmitter levels in Drosophila flight neurons. This cell-signaling mechanism is required to maintain optimal levels of a key enzyme for dopamine synthesis and may serve as a mechanism for restoring dopamine levels in relevant pathological conditions.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.1680-15.2015}, author = {Pathak, Trayambak and Agrawal, Tarjani and Richhariya, Shlesha and Sadaf, Sufia and Hasan, Gaiti} } @article {1014, title = {Structural effects of multiple pathogenic mutations suggest a model for the initiation of misfolding of the prion protein.}, journal = {Angew Chem Int Ed Engl}, volume = {54}, year = {2015}, month = {2015 Jun 22}, pages = {7529-33}, abstract = {

A molecular understanding of the prion diseases requires delineation of the origin of misfolding of the prion protein (PrP). An understanding of how different disease-linked mutations affect the structure and dynamics of native monomeric PrP can provide a clue about how misfolding commences. In this study, hydrogen-deuterium exchange mass spectrometry was used to show that several disease-linked mutant variants, which are thermodynamically destabilized, share a common structural perturbation in their native states: helix 1 is destabilized to an extent that correlates well with the destabilization of the native protein. The mutant variants misfold and form oligomers faster than does the wild-type protein, at rates that increase exponentially with the extent to which helix 1 is destabilized in the native protein. It appears, therefore, that the loss of helix 1 structure marks the beginning of PrP misfolding and oligomerization.

}, issn = {1521-3773}, doi = {10.1002/anie.201501011}, author = {Singh, Jogender and Udgaonkar, Jayant B} } @article {1009, title = {Structural Perturbations Present in the Folding Cores of Interleukin-33 and Interleukin-1β Correlate to Differences in Their Function.}, journal = {J Phys Chem B}, volume = {119}, year = {2015}, month = {2015 Aug 27}, pages = {11203-14}, abstract = {

The interleukin-1 cytokines belong to the β-trefoil fold family and play a key role in immune responses to infections and injury. We simulate the structure-based models of two interleukin-1 cytokines, IL-33 and IL-1β, and find that IL-33 has a lower barrier to folding than IL-1β. We then design the folding motif (FM) of the β-trefoil fold and identify structural deviations of IL-33 and IL-1β from this FM. In previous work, we found that structural deviations from the FM that are large enough to lower folding free energy barriers were part of ligand binding sites. In contrast, we find that structural perturbations in IL-33 and IL-1β which reduce the folding free energy barrier are located in the folding core and do not bind ligands. In both proteins, such core residues are interleaved with surface residues which are proximal to receptor binding sites. However, IL-33 has a lower folding barrier because its core perturbations are larger than those in IL-1β. In order to understand the role of these core perturbations, we perform atomistic simulations of both proteins and find that the larger core perturbations may allow IL-33 to communicate signals differently across the protein. Integrating previous data, we also hypothesize that the larger IL-33 core perturbations may help accommodate its more charged binding site and may also aid in its inactivation by caspase-mediated cleavage. Together, our results suggest that protein folding landscapes are modulated not only by larger functional features such as binding sites but also by the details of protein function and fate. Furthermore, a comparative study of such landscapes may be a facile way to identify subtle differences in allosteric connectivity between two similar proteins.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.5b03111}, author = {Giri Rao, V V Hemanth and Gosavi, Shachi} } @article {1044, title = {Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles.}, journal = {J Cell Biol}, volume = {211}, year = {2015}, month = {2015 Oct 12}, pages = {191-203}, abstract = {

Fusion of individual myoblasts to form multinucleated myofibers constitutes a widely conserved program for growth of the somatic musculature. We have used electron microscopy methods to study this key form of cell-cell fusion during development of the indirect flight muscles (IFMs) of Drosophila melanogaster. We find that IFM myoblast-myotube fusion proceeds in a stepwise fashion and is governed by apparent cross talk between transmembrane and cytoskeletal elements. Our analysis suggests that cell adhesion is necessary for bringing myoblasts to within a minimal distance from the myotubes. The branched actin polymerization machinery acts subsequently to promote tight apposition between the surfaces of the two cell types and formation of multiple sites of cell-cell contact, giving rise to nascent fusion pores whose expansion establishes full cytoplasmic continuity. Given the conserved features of IFM myogenesis, this sequence of cell interactions and membrane events and the mechanistic significance of cell adhesion elements and the actin-based cytoskeleton are likely to represent general principles of the myoblast fusion process.

}, issn = {1540-8140}, doi = {10.1083/jcb.201503005}, author = {Dhanyasi, Nagaraju and Segal, Dagan and Shimoni, Eyal and Shinder, Vera and Shilo, Ben-Zion and VijayRaghavan, K and Schejter, Eyal D} } @article {1036, title = {Systematic status of Fejervarya ((Amphibia, Anura, Dicroglossidae) from South and SE Asia with the description of a new species from the Western Ghats of Peninsular India.}, journal = {Zootaxa}, volume = {3999}, year = {2015}, month = {2015}, pages = {79-94}, abstract = {

We carried out a large-scale phylogenetic analysis of fejervaryan (dicroglossid frogs with {\textquoteright}Fejervaryan lines{\textquoteright} on the ventral side of the body) frogs, distributed in South and SE Asia, using published and newly generated sequences of unidentified individuals from the northern Western Ghats. The results corroborate the presence of a larger fejervaryan clade with a sister relationship to a clade composed of Sphaerotheca. Two sister clades could be discerned within the lager fejervaryan clade. The unidentified individuals formed a monophyletic group and showed a strong support for a sister relationship with Minervarya sahyadris. The species was found to be highly divergent (16S rRNA-4\% and tyr-1\%) from its sister lineage Minervarya sahyadris, and the clade composed of these two lineages were found to be deeply nested within the larger clade of Fejervarya. Based on this, the genus Minervarya Dubois, Ohler and Biju, 2001 is synonymized under the genus Fejervarya Bolkay, 1915. The unidentified lineage is recognized, based on phylogenetic position, genetic divergence and morphological divergence, as a distinct species and named here as Fejervarya gomantaki sp. nov. The presence of rictal glands was observed to be a synapomorphic character shared by the nested clade members, Fejervarya sahyadris and Fejervarya gomantaki sp. nov. Based on the presence of rictal gland and small size, Minervarya chilapata, a species from a lowland region in the Eastern Himalayas, is synonymized under Fejervarya and evidence for morphological separation from the new species, Fejervarya gomantaki sp. nov. is provided. For the fejervaryan frogs, currently three generic names (Frost, 2015) are available for the two phylogenetic subclades; the genus Fejervarya Bolkay, 1915 for the species of fejervaryan frogs having distribution in the South East Asia; the genus Zakerana Howlader, 2011 for the species of fejervaryan frogs having distribution in the South Asia and the genus Minervarya Dubois, Ohler and Biju, 2001 nested within the {\textquoteright}Zakerana clade{\textquoteright}. In the phylogenetic analysis Minervarya sahyadris, the new species described herein as Fejervarya gomantaki sp. nov. are nested within the {\textquoteright}Zakerana clade{\textquoteright}, if the {\textquoteright}Zakerana clade{\textquoteright} for the fejervaryan frogs having distribution in the South Asia is provided a generic status the nomen {\textquoteright}Minervarya{\textquoteright} should be considered as per the principle of priority of the ICZN Code. Taking into consideration the overlapping distribution ranges of members of the sister clades within the larger fejervaryan clade and the absence of distinct morphological characteristics, we also synonymize the genus Zakerana Howlader, 2011, a name assigned to one of the sister clades with members predominantly distributed in South Asia, under the genus Fejervarya Bolkay, 1915. We discuss the need for additional sampling to identify additional taxa and determine the geographical ranges of the members of the sister clades within Fejervarya to resolve taxonomy within this group.

}, issn = {1175-5326}, doi = {10.11646/zootaxa.3999.1.5}, author = {Dinesh, K P and Vijayakumar, S P and Channakeshavamurthy, B H and Torsekar, Varun R and Kulkarni, Nirmal U and Shanker, Kartik} } @article {867, title = {Tailor-made ezrin actin binding domain to probe its interaction with actin in-vitro.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0123428}, abstract = {

Ezrin, a member of the ERM (Ezrin/Radixin/Moesin) protein family, is an Actin-plasma membrane linker protein mediating cellular integrity and function. In-vivo study of such interactions is a complex task due to the presence of a large number of endogenous binding partners for both Ezrin and Actin. Further, C-terminal actin binding capacity of the full length Ezrin is naturally shielded by its N-terminal, and only rendered active in the presence of Phosphatidylinositol bisphosphate (PIP2) or phosphorylation at the C-terminal threonine. Here, we demonstrate a strategy for the design, expression and purification of constructs, combining the Ezrin C-terminal actin binding domain, with functional elements such as fusion tags and fluorescence tags to facilitate purification and fluorescence microscopy based studies. For the first time, internal His tag was employed for purification of Ezrin actin binding domain based on in-silico modeling. The functionality (Ezrin-actin interaction) of these constructs was successfully demonstrated by using Total Internal Reflection Fluorescence Microscopy. This design can be extended to other members of the ERM family as well.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0123428}, author = {Shrivastava, Rohini and K{\"o}ster, Darius and Kalme, Sheetal and Mayor, Satyajit and Neerathilingam, Muniasamy} } @article {890, title = {Tracing the geographic origin of traded leopard body parts in the indian subcontinent with DNA-based assignment tests.}, journal = {Conserv Biol}, volume = {29}, year = {2015}, month = {2015 Apr}, pages = {556-64}, abstract = {

Illicit trade in wildlife products is rapidly decimating many species across the globe. Such trade is often underestimated for wide-ranging species until it is too late for the survival of their remaining populations. Policing this trade could be vastly improved if one could reliably determine geographic origins of illegal wildlife products and identify areas where greater enforcement is needed. Using DNA-based assignment tests (i.e., samples are assigned to geographic locations), we addressed these factors for leopards (Panthera pardus) on the Indian subcontinent. We created geography-specific allele frequencies from a genetic reference database of 173 leopards across India to infer geographic origins of DNA samples from 40 seized leopard skins. Sensitivity analyses of samples of known geographic origins and assignments of seized skins demonstrated robust assignments for Indian leopards. We found that confiscated pelts seized in small numbers were not necessarily from local leopards. The geographic footprint of large seizures appeared to be bigger than the cumulative footprint of several smaller seizures, indicating widespread leopard poaching across the subcontinent. Our seized samples had male-biased sex ratios, especially the large seizures. From multiple seized sample assignments, we identified central India as a poaching hotspot for leopards. The techniques we applied can be used to identify origins of seized illegal wildlife products and trade routes at the subcontinent scale and beyond.

}, issn = {1523-1739}, doi = {10.1111/cobi.12393}, author = {Mondol, Samrat and Sridhar, Vanjulavalli and Yadav, Prasanjeet and Gubbi, Sanjay and Ramakrishnan, Uma} } @article {881, title = {Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins.}, journal = {Cell}, volume = {161}, year = {2015}, month = {2015 Apr 23}, pages = {581-94}, abstract = {

Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesterol-dependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chain-containing phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.

}, keywords = {Actins, Animals, Cell Membrane, CHO Cells, Cricetulus, Glycosylphosphatidylinositols, Lipid-Linked Proteins, Molecular Dynamics Simulation, Phosphatidylserines}, issn = {1097-4172}, doi = {10.1016/j.cell.2015.03.048}, author = {Raghupathy, Riya and Anilkumar, Anupama Ambika and Polley, Anirban and Singh, Parvinder Pal and Yadav, Mahipal and Johnson, Charles and Suryawanshi, Sharad and Saikam, Varma and Sawant, Sanghapal D and Panda, Aniruddha and Guo, Zhongwu and Vishwakarma, Ram A and Rao, Madan and Mayor, Satyajit} } @article {1013, title = {Tuning Cooperativity on the Free Energy Landscape of Protein Folding.}, journal = {Biochemistry}, volume = {54}, year = {2015}, month = {2015 Jun 9}, pages = {3431-41}, abstract = {

Understanding the origin of the cooperativity seemingly inherent in a folding or unfolding reaction has been a major challenge. In particular, the relationship between folding cooperativity and stability is poorly understood. In this study, native state hydrogen exchange in conjunction with mass spectrometry has been used to explore the free energy landscape accessible to the small protein monellin, when the stability of the protein is varied. Mass distributions obtained in the EX1 limit of exchange have allowed a direct distinction between correlated (cooperative) and uncorrelated (noncooperative) structure-opening processes. Under conditions where the native protein is maximally stable, a continuum of partially unfolded states is gradually sampled before the globally unfolded state is transiently sampled. Under conditions that stabilize the unfolded state of the protein, the slowest structure-opening reactions leading to complete unfolding become cooperative. The present study provides experimental evidence for a gradual uphill unfolding transition on a very slow time scale, in the presence of a large free energy difference between the native and unfolded states. The results suggest that the cooperativity that manifests itself in protein folding and unfolding reactions carried out in the presence of denaturant might merely be a consequence of the effect of the denaturant on the unfolded state and transition state stabilities.

}, keywords = {Models, Chemical, Plant Proteins, Protein Folding, Protein Structure, Tertiary}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5b00247}, author = {Malhotra, Pooja and Udgaonkar, Jayant B} } @article {913, title = {Tuning the pH Response of i-Motif DNA Oligonucleotides.}, journal = {Chembiochem}, volume = {16}, year = {2015}, month = {2015 Jul 27}, pages = {1647-56}, abstract = {

Cytosine-rich single-stranded DNA oligonucleotides are able to adopt an i-motif conformation, a four-stranded structure, near a pH of 6. This unique pH-dependent conformational switch is reversible and hence can be controlled by changing the pH. Here, we show that the pH response range of the human telomeric i-motif can be shifted towards more basic pH values by introducing 5-methylcytidines (5-MeC) and towards more acidic pH values by introducing 5-bromocytidines (5-BrC). No thermal destabilisation was observed in these chemically modified i-motif sequences. The time required to attain the new conformation in response to sudden pH changes was slow for all investigated sequences but was found to be ten times faster in the 5-BrC derivative of the i-motif.

}, issn = {1439-7633}, doi = {10.1002/cbic.201500182}, author = {Lannes, Laurie and Halder, Saheli and Krishnan, Yamuna and Schwalbe, Harald} } @article {856, title = {Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.}, journal = {Structure}, volume = {23}, year = {2015}, month = {2015 Jan 6}, pages = {56-67}, abstract = {

The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E.\ coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E.\ coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E.\ coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics.

}, keywords = {Anti-Bacterial Agents, Crystallography, X-Ray, DNA Adducts, DNA Polymerase beta, Drug Resistance, Bacterial, Escherichia coli, Escherichia coli Proteins, Models, Molecular, Nitrofurazone, Nitrogen Compounds, Protein Structure, Tertiary, Reactive Nitrogen Species}, issn = {1878-4186}, doi = {10.1016/j.str.2014.10.019}, author = {Kottur, Jithesh and Sharma, Amit and Gore, Kiran R and Narayanan, Naveen and Samanta, Biswajit and Pradeepkumar, Pushpangadan I and Nair, Deepak T} } @article {1018, title = {Vesicular trafficking and salinity responses in plants.}, journal = {IUBMB Life}, volume = {67}, year = {2015}, month = {2015 Sep}, pages = {677-86}, abstract = {

Research spanning three decades has demonstrated that vesicles pinch off from the plasma membrane and traffic through the cytoplasm of plant cells, much as previously reported in animal cells. Although the well-conserved clathrin-mediated mechanism of endocytosis has been well characterized, relatively little is known about clathrin-independent pathways in plants. Modulation of endocytosis by both physical stimuli and chemical ligands has been reported in plants. Here, we review the effect of salinity-one of the most deleterious environmental assaults-on endocytosis and intracellular trafficking. {\textcopyright} 2015 IUBMB Life, 67(9):677-686, 2015.

}, issn = {1521-6551}, doi = {10.1002/iub.1425}, author = {Baral, Anirban and Shruthi, K S and Mathew, M K} } @article {1025, title = {Why do bacteria regulate public goods by quorum sensing?-How the shapes of cost and benefit functions determine the form of optimal regulation.}, journal = {Front Microbiol}, volume = {6}, year = {2015}, month = {2015}, pages = {767}, abstract = {

Many bacteria secrete compounds which act as public goods. Such compounds are often under quorum sensing (QS) regulation, yet it is not understood exactly when bacteria may gain from having a public good under QS regulation. Here, we show that the optimal public good production rate per cell as a function of population size (the optimal production curve, OPC) depends crucially on the cost and benefit functions of the public good and that the OPC will fall into one of two categories: Either it is continuous or it jumps from zero discontinuously at a critical population size. If, e.g., the public good has accelerating returns and linear cost, then the OPC is discontinuous and the best strategy thus to ramp up production sharply at a precise population size. By using the example of public goods with accelerating and diminishing returns (and linear cost) we are able to determine how the two different categories of OPSs can best be matched by production regulated through a QS signal feeding back on its own production. We find that the optimal QS parameters are different for the two categories and specifically that public goods which provide accelerating returns, call for stronger positive signal feedback.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2015.00767}, author = {Heilmann, Silja and Krishna, Sandeep and Kerr, Benjamin} } @article {1637, title = {Zebra finch as a developmental model.}, journal = {Genesis}, volume = {53}, year = {2015}, month = {2015 Nov}, pages = {669-77}, abstract = {

The domesticated zebra finch (Taeniopygia guttata) is a well-established animal model for studying vocal learning. It is also a tractable model for developmental analyses. The finch genome has been sequenced and methods for its transgenesis have been reported. Hatching and sexual maturation in this species takes only two weeks and three months, respectively. Finch colonies can be established relatively easily and its eggs are laid at a stage earlier than in other common avian experimental models, facilitating the analysis of very early avian development. Representing the Neoaves to which 95\% of all bird species belong, the finch can potentially complement two existing, Galloanserae developmental models, the chick, and quail. Here, we provide a step-by-step guide for how to set up a finch colony in a conventional laboratory environment. Technical tips are offered to optimize hens{\textquoteright} productivity and ensure a constant supply of fertilized finch eggs. Methods of handling finch eggs and embryos for subsequent embryological, cellular, or molecular analyses are also discussed. We conclude by emphasizing scientific values and cost effectiveness of maintaining a finch colony for avian developmental studies. genesis 53:669-677, 2015. {\textcopyright} 2015 Wiley Periodicals, Inc.

}, issn = {1526-968X}, doi = {10.1002/dvg.22900}, author = {Mak, Siu-Shan and Wrabel, Anna and Nagai, Hiroki and Ladher, Raj K and Sheng, Guojun} } @article {127108, title = {Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.}, journal = {BMC Genomics}, volume = {15}, year = {2014}, month = {2014 Dec 02}, pages = {1049}, abstract = {

BACKGROUND: Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs. Expression levels of AGOs are greatly regulated by plants in order to minimize unwarranted perturbations using miRNAs to target mRNAs coding for AGOs. AGOs may also have high promoter specificity-sometimes expression of AGO can be limited to just a few cells in a plant. Viral pathogens utilize various means to counter antiviral roles of AGOs including hijacking the host encoded miRNAs to target AGOs. Two host encoded miRNAs namely miR168 and miR403 that target AGOs have been described in the model plant Arabidopsis and such a mechanism is thought to be well conserved across plants because AGO sequences are well conserved.

RESULTS: We show that the interaction between AGO mRNAs and miRNAs is species-specific due to the diversity in sequences of two miRNAs that target AGOs, sequence diversity among corresponding target regions in AGO mRNAs and variable expression levels of these miRNAs among vascular plants. We used miRNA sequences from 68 plant species representing 31 plant families for this analysis. Sequences of miR168 and miR403 are not conserved among plant lineages, but surprisingly they differ drastically in their sequence diversity and expression levels even among closely related plants. Variation in miR168 expression among plants correlates well with secondary structures/length of loop sequences of their precursors.

CONCLUSIONS: Our data indicates a complex AGO targeting interaction among plant lineages due to miRNA sequence diversity and sequences of miRNA targeting regions among AGO mRNAs, thus leading to the assumption that the perturbations by viruses that use host miRNAs to target antiviral AGOs can only be species-specific. We also show that rapid evolution and likely loss of expression of miR168 isoforms in tobacco is related to the insertion of MITE-like transposons between miRNA and miRNA* sequences, a possible mechanism showing how miRNAs are lost in few plant lineages even though other close relatives have abundantly expressing miRNAs.

}, keywords = {Argonaute Proteins, Base Sequence, Binding Sites, Disease Resistance, Gene Dosage, Gene Expression Regulation, Plant, Genetic Variation, Genotype, Host-Pathogen Interactions, MicroRNAs, Molecular Sequence Data, Nucleic Acid Conformation, Plants, RNA Precursors, RNA, Messenger, RNA, Plant, Sequence Alignment, Species Specificity}, issn = {1471-2164}, doi = {10.1186/1471-2164-15-1049}, author = {Jagtap, Soham and Shivaprasad, Padubidri V} } @article {80913, title = {Pathways of clathrin-independent endocytosis.}, journal = {Nat Rev Mol Cell Biol}, volume = {8}, year = {2007}, month = {2007 Aug}, pages = {603-12}, abstract = {

There are numerous ways that endocytic cargo molecules may be internalized from the surface of eukaryotic cells. In addition to the classical clathrin-dependent mechanism of endocytosis, several pathways that do not use a clathrin coat are emerging. These pathways transport a diverse array of cargoes and are sometimes hijacked by bacteria and viruses to gain access to the host cell. Here, we review our current understanding of various clathrin-independent mechanisms of endocytosis and propose a classification scheme to help organize the data in this complex and evolving field.

}, keywords = {Animals, Bacteria, Biological Transport, Active, Clathrin, Endocytosis, Eukaryotic Cells, Humans, Virus Internalization, Viruses}, issn = {1471-0072}, doi = {10.1038/nrm2216}, author = {Mayor, Satyajit and Pagano, Richard E} } @article {19527, title = {Activation of alpha 1-adrenoceptors increases [3H]inositol metabolism in rat vas deferens and caudal artery.}, journal = {Eur J Pharmacol}, volume = {116}, year = {1985}, month = {1985 Oct 08}, pages = {145-52}, abstract = {

Rings of rat vas deferens and caudal artery were incubated with [3H]inositol in Krebs-Ringer bicarbonate buffer containing 10 mM lithium chloride, and the production of water-soluble [3H]inositol phosphates was monitored. Norepinephrine increased [3H]inositol phosphate accumulation 7-fold in rings from vas deferens and 3-fold in rings from caudal artery. Epinephrine, phenylephrine and methoxamine were as effective as norepinephrine, suggesting that these drugs are full agonists in causing this response. Prazosin, phentolamine and yohimbine completely blocked the stimulation by norepinephrine in both tissues with potencies typical of blockade of alpha 1-adrenoceptors. Despite a substantial receptor reserve for alpha 1-adrenoceptor mediated contractile responses, clonidine, p-amino-clonidine, phenylpropanolamine and ephedrine can only cause a partial contractile response in rat vas deferens. However, all of these partial agonists were either as effective or more effective in increasing [3H]inositol phosphate accumulation in rat vas deferens as they were in activating a contractile response. These data suggest that alpha 1-adrenoceptors increase phosphatidylinositol turnover in rat vas deferens and caudal artery, and that there may be a receptor reserve for alpha 1-adrenoceptor mediated increases in [3H]inositol phosphate accumulation in these smooth muscles.

}, keywords = {Adrenergic alpha-Agonists, Adrenergic alpha-Antagonists, Animals, Arteries, In Vitro Techniques, Inositol, Inositol Phosphates, Male, Muscle, Smooth, Muscle, Smooth, Vascular, Rats, Rats, Inbred Strains, Receptors, Adrenergic, alpha, Vas Deferens}, issn = {0014-2999}, author = {Fox, A W and Abel, P W and Minneman, K P} } @article {159723, title = {Increase in acetyl CoA synthetase activity after phenobarbital treatment.}, journal = {Biochem Pharmacol}, volume = {24}, year = {1975}, month = {1975 Sep 15}, pages = {1725-7}, keywords = {Acetate-CoA Ligase, Acetylesterase, Acetylglucosamine, Animals, Coenzyme A Ligases, Cycloheximide, Glucosamine, Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), Liver, Male, Phenobarbital, Phosphotransferases, Proteins, Rats, Stimulation, Chemical}, issn = {0006-2952}, doi = {10.1016/0006-2952(75)90013-1}, author = {Akamatsu, N and Nakajima, H and Ono, M and Miura, Y} }