Biology subjects

Gay, M.

Publications and source records attributed to Gay, M..

6 recordsLinked to original sources

bioRxiv2025

Dried Blood Spot Lipidomics in Diabetes

Comprehensive lipidomic profiling in diabetes has identified disease-associated lipid signatures that may support more personalised monitoring beyond routine glycaemic control. Dried blood spot (DBS) microsampling offers a minimally invasive method for collecting and storing small blood volumes (<50 {micro}L), enabling decentralised and longitudinal sampling. However, its application in lipidomics for cardiometabolic phenotyping remains underexplored. In this study, 34 participants (17 diabetics, 17 non-diabetic controls) self-collected DBS samples using advanced microsampling devices (10 {micro}L, Capitainer(R)B). Lipid extracts were analysed using a validated liquid chromatography-trapped ion mobility-time-of-flight mass spectrometry method optimised for semi-quantitative DBS lipidomics. Multivariate analysis revealed significant differences in lipidomic profiles (n = 432 lipids) between diabetic and non-diabetic individuals (R{superscript 2}Y = 0.82, Q{superscript 2}Y = 0.50, p = 0.05). Key discriminatory lipids (all VIP > 1.44), including HexCer(18:1;O2/24:0), HexCer(18:1;O2/22:0), LPC(16:0), PC(O-34:3), TG(18:0_18:1_20:3), and TG(18:1_18:1_22:6), were consistent with matched venous and capillary plasma samples. Lipid class and structural differences, including elevated long-chain triacylglycerols and reduced lysophosphatidylcholines reflected known dyslipidaemia in diabetes and demonstrate the capacity of DBS to capture biologically meaningful lipid perturbations. Participant-reported outcomes from Problem Areas In Diabetes (PAID-20), Patient Activation Measure (PAM-13), and microsampling perception questionnaires highlighted psychosocial and behavioural insights, and indicated strong support for DBS sampling over venepuncture, citing ease of use and reduced burden. These findings establish DBS lipidomics as a feasible and informative approach for stratifying cardiometabolic disease, supporting broader implementation in remote, personalised monitoring frameworks (Figure 1). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/656742v1_fig1.gif" ALT="Figure 1"> View larger version (13K): org.highwire.dtl.DTLVardef@c53b4org.highwire.dtl.DTLVardef@14b507forg.highwire.dtl.DTLVardef@191e563org.highwire.dtl.DTLVardef@16af172_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Graphical abstract - Chapter 5. C_FIG

biochemistry↗

bioRxiv2025

Anaesthesia disrupts mesoscale signal propagation in spite of enhanced responsivity in frontal but not in parietal cortex

Loss of consciousness under anaesthesia is accompanied by widespread silencing of neurons, and disruption of cortical dynamics. Yet, how this affects mesoscale signal propagation within higher-order associative areas, crucially implicated in theories of consciousness, remains poorly understood. Here we combined intracortical microstimulation, and simultaneous multielectrode recordings in the ventrolateral prefrontal cortex (vlPFC) and the posterior parietal cortex (PPC) of macaques across wakefulness, and graded depths of anaesthesia. Spiking responses revealed distinct regimes: in the PFC, higher-amplitude stimulation elicited a delayed single rebound after sustained inhibition, whereas in the PPC, a faster and double-rebound profile emerged. Despite enhanced local spiking and LFP responsivity under anaesthesia, we found a strong and selective suppression of lateral signal propagation in the PFC - a breakdown strikingly absent in the PPC. This dissociation suggests that anaesthesia disrupts consciousness not merely by silencing cortical populations, but by impairing mesoscale integrative processes critical for neuronal dynamics at multiple scales. Our findings demonstrate in a causal and spatially-resolved manner, that lateral signal spread within higher-order cortex is a key mechanism underlying conscious awareness, and its loss under anaesthesia.

neuroscience↗

bioRxiv2022

Characterization of p38a signaling networks in cancer cells using quantitative proteomics and phosphoproteomics

p38 (encoded by MAPK14) is a protein kinase that regulates cellular responses to almost all types of environmental and intracellular stresses. Upon activation, p38 phosphorylates many substrates both in the cytoplasm and nucleus, allowing this pathway to regulate a wide variety of cellular processes. While the role of p38 in the stress response has been widely investigated, its implication in cell homeostasis is less understood. To investigate the signaling networks regulated by p38 in normally proliferating cancer cells, we performed quantitative proteomic and phosphoproteomic analyses in breast cancer cells in which this pathway had been either genetically targeted or chemically inhibited. Our study identified with high confidence 35 proteins and 82 phosphoproteins (114 phosphosites) that are modulated by p38, and highlighted the implication of various protein kinases, including MK2 and mTOR, in the p38-regulated signaling networks. Moreover, functional analyses revealed an important contribution of p38 to the regulation of cell adhesion, DNA replication and RNA metabolism. Indeed, we provide experimental evidence supporting that p38 negatively regulates cell adhesion, and showed that this p38 function is likely mediated by the modulation of the adaptor protein ArgBP2. Collectively, our results illustrate the complexity of the p38 regulated signaling networks, provide valuable information on p38-dependent phosphorylation events in cancer cells, and document a mechanism by which p38 can regulate cell adhesion.

biochemistry↗

bioRxiv2021

Prefrontal neural ensembles encode an internal model of visual sequences and their violations

When exposed to sensory sequences, do macaque monkeys spontaneously form abstract internal models that generalize to novel experiences? Here, we show that neuronal populations in macaque ventrolateral prefrontal cortex encode visual sequences by factorizing them into separate codes for the specific pictures presented and for their abstract sequential structure. Ventrolateral prefrontal neurons were recorded while macaque monkeys passively viewed visual sequences and sequence mismatches in the local-global paradigm. Even without any overt task or response requirements, prefrontal populations spontaneously built up representations of sequence structure, serial order, and image identity within distinct but superimposed neuronal subspaces. Representations of sequence structure rapidly updated following single exposure to a mismatch sequence, while orthogonal populations represent mismatches for sequences of different complexity. Finally, those representations generalized across sequences following the same structure but comprising different images. These results suggest that prefrontal populations spontaneously encode rich internal models of visual sequences that reflect both content-specific and abstract information.

neuroscience↗

bioRxiv2021

Identification and drug-induced reversion of molecular signatures of Alzheimers disease onset and progression in AppNL-G-F, AppNL-F and 3xTg-AD mouse models

Alzheimers disease (AD) is the most common form of dementia. Over fifty years of intense research have revealed many key elements of the biology of this neurodegenerative disorder. However, our understanding of the molecular bases of the disease is still incomplete, and the medical treatments available for AD are mainly symptomatic and hardly effective. Indeed, the robustness of biological systems has revealed that the modulation of a single target is unlikely to yield the desired outcome and we should therefore move from gene-centric to systemic therapeutic strategies. Here we present the complete characterization of three murine models of AD at different stages of the disease (i.e. onset, progression and advanced). To identify genotype-to-phenotype relationships, we combine the cognitive assessment of these mice with histological analyses and full transcriptional and protein quantification profiling of the hippocampus. Comparison of the gene and protein expression trends observed in AD progression and physiological aging revealed certain commonalities, such as the upregulation of microglial and inflammation markers. However, although AD models show accelerated aging, other factors specifically associated with A{beta} pathology are involved. Despite the clear correlation between mRNA and protein levels of the dysregulated genes, we discovered a few proteins whose abundance increases with AD progression, while the corresponding transcript levels remain stable. Indeed, we show that at least two of these proteins, namely lfit3 and Syt11, co-localize with A{beta} plaques in the brain. Finally, we derived specific A{beta}-related molecular AD signatures and looked for drugs able to globally revert them. We found two NSAIDs (dexketoprofen and etodolac) and two anti-hypertensives (penbutolol and bendroflumethiazide) that overturn the cognitive impairment in AD mice while reducing A{beta} plaques in the hippocampus and partially restoring the physiological levels of AD signature genes to wild-type levels. TeaserThe comprehensive characterization of three AD mouse models reveals disease signatures that we used to identify approved drugs able to modify the etiology of the pathology and overturn cognitive impairment.

neuroscience↗

bioRxiv2018

Cross-linking/Mass Spectrometry: A Community-Wide, Comparative Study Towards Establishing Best Practice Guidelines

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has largely increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats that are generally accepted in the field and that have shown to lead to high-quality results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. From the results obtained, common protocols will be established. Our study serves as basis for establishing best practice guidelines in the field for conducting cross-linking experiments, performing data analysis, and reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results.

biochemistry↗