@article {149407, title = {Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Oct 03}, pages = {8562}, abstract = {

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

}, keywords = {Calibration, Ceramides, Humans, Laboratories, Lipidomics, Mass Spectrometry, Reference Standards, Reproducibility of Results}, issn = {2041-1723}, doi = {10.1038/s41467-024-52087-x}, author = {Torta, Federico and Hoffmann, Nils and Burla, Bo and Alecu, Irina and Arita, Makoto and Bamba, Takeshi and Bennett, Steffany A L and Bertrand-Michel, Justine and Br{\"u}gger, Britta and Cala, M{\'o}nica P and Camacho-Mu{\~n}oz, Dolores and Checa, Antonio and Chen, Michael and Chocholou{\v s}kov{\'a}, Michaela and Cinel, Michelle and Chu-Van, Emeline and Colsch, Benoit and Coman, Cristina and Connell, Lisa and Sousa, Bebiana C and Dickens, Alex M and Fedorova, Maria and Eir{\'\i}ksson, Finnur Freyr and Gallart-Ayala, Hector and Ghorasaini, Mohan and Giera, Martin and Guan, Xue Li and Haid, Mark and Hankemeier, Thomas and Harms, Amy and H{\"o}ring, Marcus and Hol{\v c}apek, Michal and Hornemann, Thorsten and Hu, Chunxiu and H{\"u}lsmeier, Andreas J and Huynh, Kevin and Jones, Christina M and Ivanisevic, Julijana and Izumi, Yoshihiro and K{\"o}feler, Harald C and Lam, Sin Man and Lange, Mike and Lee, Jong Cheol and Liebisch, Gerhard and Lippa, Katrice and Lopez-Clavijo, Andrea F and Manzi, Malena and Martinefski, Manuela R and Math, Raviswamy G H and Mayor, Satyajit and Meikle, Peter J and Monge, Mar{\'\i}a Eugenia and Moon, Myeong Hee and Muralidharan, Sneha and Nicolaou, Anna and Nguyen-Tran, Thao and O{\textquoteright}Donnell, Valerie B and Ore{\v s}i{\v c}, Matej and Ramanathan, Arvind and Riols, Fabien and Saigusa, Daisuke and Schock, Tracey B and Schwartz-Zimmermann, Heidi and Shui, Guanghou and Singh, Madhulika and Takahashi, Masatomo and Thorsteinsd{\'o}ttir, Margr{\'e}t and Tomiyasu, Noriyuki and Tournadre, Anthony and Tsugawa, Hiroshi and Tyrrell, Victoria J and van der Gugten, Grace and Wakelam, Michael O and Wheelock, Craig E and Wolrab, Denise and Xu, Guowang and Xu, Tianrun and Bowden, John A and Ekroos, Kim and Ahrends, Robert and Wenk, Markus R} } @article {97218, title = {Sphingolipid metabolism during TLR4-mediated macrophage activation.}, journal = {Br J Pharmacol}, year = {2021}, month = {2021 Aug 06}, abstract = {

Macrophage activation in response to stimulation of Toll-like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulate the inflammatory response. TLR4-mediated pro-inflammatory macrophage activation is characterised by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompany classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here we review the importance of TLR4-mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4-driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasise the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro-inflammatory and pro-resolution phases of LPS/TLR4 activation in macrophages.

}, issn = {1476-5381}, doi = {10.1111/bph.15642}, author = {Olona, Antoni and Hateley, Charlotte and Muralidharan, Sneha and Wenk, Markus R and Torta, Federico and Behmoaras, Jacques} } @article {80781, title = {The bacterial quorum sensing signal DSF hijacks sterol biosynthesis to suppress plant innate immunity.}, journal = {Life Sci Alliance}, volume = {3}, year = {2020}, month = {2020 Oct}, abstract = {

Quorum sensing (QS) is a recognized phenomenon that is crucial for regulating population-related behaviors in bacteria. However, the direct specific effect of QS molecules on host biology is largely understudied. In this work, we show that the QS molecule DSF (-11-methyl-dodecenoic acid) produced by pv. can suppress pathogen-associated molecular pattern-triggered immunity (PTI) in , mediated by flagellin-induced activation of flagellin receptor FLS2. The DSF-mediated attenuation of innate immunity results from the alteration of FLS2 nanoclusters and endocytic internalization of plasma membrane FLS2. DSF altered the lipid profile of , with a particular increase in the phytosterol species, which impairs the general endocytosis pathway mediated by clathrin and FLS2 nano-clustering on the plasma membrane. The DSF effect on receptor dynamics and host immune responses could be entirely reversed by sterol removal. Together, our results highlighted the importance of sterol homeostasis to plasma membrane organization and demonstrate a novel mechanism by which pathogenic bacteria use their communicating molecule to manipulate pathogen-associated molecular pattern-triggered host immunity.

}, issn = {2575-1077}, doi = {10.26508/lsa.202000720}, author = {Tran, Tuan Minh and Ma, Zhiming and Triebl, Alexander and Nath, Sangeeta and Cheng, Yingying and Gong, Ben-Qiang and Han, Xiao and Wang, Junqi and Li, Jian-Feng and Wenk, Markus R and Torta, Federico and Mayor, Satyajit and Yang, Liang and Miao, Yansong} }