Biology subjects

David, L. C.

Publications and source records attributed to David, L. C..

3 recordsLinked to original sources

bioRxiv2026

The Evolving Bileome: A Pan-Repository Landscape of Expanded Bile Acid and Related Steroidal Signatures

Bile acids and related steroidal metabolites are among the most studied biomolecules, yet recent work has revealed far greater structural diversity than previously recognized, much of it shaped by the microbiome. We previously introduced a repository-scale bile acid MS/MS library built from queries targeting C24 bile acid fragmentation, limited to Orbitrap Q Exactive datasets within GNPS/MassIVE. Here we announce a major expansion of this library: a bile acid and steroidal MS/MS spectral library assembled across three major metabolomics repositories, now capturing C23, C24 (including alkamine), C26 (C-C bonded aceto derivatives), and C27 bile acids, as well as C28 bile alcohols. The expanded libraries comprise 640,141 unique MS/MS spectra, of which 120,293 (18.8%) match 2,529 reference spectra, leaving most of this steroidal chemical space structurally unassigned. Linked to harmonized pan-repository metadata, the library provides a starting point for classifying MS/MS spectra as likely bile acids or related steroids, with two example analyses illustrated here. This resource allows researchers to flag candidate bile acid and steroidal signatures in their own data for further characterization.

bioinformatics↗

bioRxiv2026

Serum metabolic signatures of cognitive resilience in a longitudinal aging cohort

Aging is typically accompanied by a progressive decline in cognitive function, yet some individuals maintain exceptional cognitive performance, even across the transition from middle to older age, defining exceptional cognitive resilience. While existing measures of resilience primarily rely on clinical assessments, its molecular determinants and early predictive markers remain poorly understood. Here, we performed untargeted LC-MS/MS profiling of longitudinal serum samples to identify metabolic signatures associated with cognitive resilience, which was established based on cognitive tests conducted over 28 years in a cohort of 237 participants. We observed associations across multiple chemical classes, including carnitines, glutamine conjugates, phosphocholines, as well as diet-and drug-derived metabolites. Chemical class-specific analyses revealed distinct metabolic profiles, including predominantly negative associations of medium-chain acylcarnitines with cognitive resilience, increased accumulation of glucuronide conjugates in individuals with low cognitive resilience, altered metabolism of the antihypertensive drug, metoprolol, and elevated levels of dietary compounds such as piperine and lutein in individuals with high cognitive resilience. By leveraging public metabolomics data, we further contextualized the metabolic signatures with respect to their organ specificity, microbial origin, and disease associations. Collectively, these metabolic features, including several previously underexplored compounds, represent promising candidates for functional characterization in mechanisms of aging biology and provide mechanistic insights into the molecular basis of cognitive resilience. HighlightsO_LISerum metabolite MS/MS features, including acyl carnitines, phosphocholines, and hippuric acid conjugates, are associated with cognitive resilience in 237 individuals transitioning from middle to older age. C_LIO_LIDiet-derived piperine is positively associated with cognitive resilience. C_LIO_LIDifferences in {beta}-blocker drug metabolism, rather than parent drug levels, are associated with cognitive resilience. C_LIO_LIRepository-scale searches for the resilience-associated metabolites reveal organ specificity, microbial contributions, and their presence across multiple disease contexts. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/715122v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1038203org.highwire.dtl.DTLVardef@14ca5f1org.highwire.dtl.DTLVardef@12275fcorg.highwire.dtl.DTLVardef@16ff70c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

BdNRT2A and BdNRT3.2 are the major components of the High-Affinity nitrate Transport System in Brachypodium distachyon

O_LIAn efficient nitrate uptake system contributes to the improvement of crop nitrogen use efficiency under low nitrogen availability. The High Affinity nitrate Transport System (HATS) in plants is active in low external nitrate and is mediated by a two-component system [high affinity transporters NRT2 associated to a partner protein NRT3 (NAR2)]. C_LIO_LIIn Brachypodium, the model plant for C3 cereals, we investigated the role of BdNRT2A and BdNRT3.2 through various experimental approaches including gene expression profiling, functional characterisation in heterologous system, intracellular localization by imaging, and reverse genetics via gene silencing. C_LIO_LIExpression of BdNRT2.A and BdNRT3.2 genes in response to nitrate availability fits with the characteristics of the HATS components. Co-expression of BdNRT2A and BdNRT3.2 is required for an effective nitrate transport in the heterologous expression system Xenopus oocytes. Functional interaction between BdNRT2A-GFP and BdNRT3.2-RFP fusion proteins has been observed at the plasma membrane in Arabidopsis protoplasts in transient expression experiments. BdNRT3.2 appeared to be necessary for the plasma membrane localization of BdNRT2A. 15Nitrate influx measurements with bdnrt2a mutants (two amiRNA mutants and one NaN3 induced mutant with a truncated NRT2A protein), confirmed that BdNRT2A is a major contributor of the HATS in Brachypodium. C_LIO_LIDirected mutagenesis in BdNRT2A of a conserved Ser residue (S461) specific to monocotyledons has been performed to mimic a non-phosphorylated S461A or a constitutively phosphorylated S461D, in order to evaluate its potential role in the BdNRT2A and BdNRT3.2 interaction leading to plasma membrane targeting. Interestingly, the phosphorylation status of S461 did not modify the interaction, suggesting on a more complex mechanism. C_LIO_LIIn conclusion, our data show that BdNRT2A and BdNRT3.2 are the main components of the nitrate HATS activity in Brachypodium (Bd21-3) and allow an optimal growth in low N conditions. C_LI

plant biology↗