@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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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} } @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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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} }