Loïc Dayon - Academia.edu (original) (raw)

Papers by Loïc Dayon

Rapid Communications in Mass Spectrometry, 2009

Diabetologia

Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic ... more Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress. Methods Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.1 mmol/l glucose. Metabolomics was applied to analyse intracellular metabolite changes as a result of glucose stress conditions. Alterations in beta cell function were followed using insulin secretion assays or cytosolic calcium signalling after expression of the calcium probe YC3.6 specifically in beta cells of islet clusters. Results At early stages of glucose stress, mitochondrial energy metabolism was augmented in contrast to the previously described mitochondrial dysfunction in beta cells from islets of diabetic donors. Following chronic glucose stress, mitochondrial respiration incr...

Methods in Molecular Biology

PROTEOMICS - Clinical Applications

Journal of Molecular Biology

Journal of Proteome Research

Current Topics in Behavioral Neurosciences

Alzheimer's Research & Therapy

Background: Altered proteome profiles have been reported in both postmortem brain tissues and bod... more Background: Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and taurelated neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology. Methods: Cross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72). LC-MS quantified hundreds of proteins in the CSF. CSF concentrations of β-amyloid 1-42 (Aβ 1-42), tau, and tau phosphorylated at threonine 181 (P-tau181) were determined with immunoassays. First, we explored proteins relevant to biomarker-defined AD. Then, correlation analysis of CSF proteins with CSF markers of amyloid pathology, neuronal injury, and tau hyperphosphorylation (i.e., Aβ 1-42 , tau, P-tau181) was performed using Pearson's correlation coefficient and Bonferroni correction for multiple comparisons. Results: We quantified 790 proteins in CSF samples with MS. Four CSF proteins showed an association with CSF Aβ 1-42 levels (p value ≤ 0.05 with correlation coefficient (R) ≥ 0.38). We identified 50 additional CSF proteins associated with CSF tau and 46 proteins associated with CSF P-tau181 (p value ≤ 0.05 with R ≥ 0.37). The majority of those proteins that showed such associations were brain-enriched proteins. Gene Ontology annotation revealed an enrichment for synaptic proteins and proteins originating from reelin-producing cells and the myelin sheath. Conclusions: We used an MS-based proteomic workflow to profile the CSF proteome in relation to cerebral AD pathology. We report strong evidence of previously reported CSF proteins and several novel CSF proteins specifically associated with amyloid pathology or neuronal injury and tau hyperphosphorylation.

Journal of proteome research, Jan 6, 2018

Over the last two decades, EDTA-plasma has been used as the preferred sample matrix for human blo... more Over the last two decades, EDTA-plasma has been used as the preferred sample matrix for human blood proteomic profiling. Serum has also been employed widely. Only a few studies have assessed the difference and relevance of the proteome profiles obtained from plasma samples, such as EDTA-plasma or lithium-heparin-plasma, and serum. A more complete evaluation of the use of EDTA-plasma, heparin-plasma, and serum would greatly expand the comprehensiveness of shotgun proteomics of blood samples. In this study, we evaluated the use of heparin-plasma with respect to EDTA-plasma and serum to profile blood proteomes using a scalable automated proteomic pipeline (ASAP). The use of plasma and serum for mass-spectrometry-based shotgun proteomics was first tested with commercial pooled samples. The proteome coverage consistency and the quantitative performance were compared. Furthermore, protein measurements in EDTA-plasma and heparin-plasma samples were comparatively studied using matched sampl...

Proteomics. Clinical applications, 2018

Cell reports, Jan 15, 2017

Lysine acetylation is involved in various biological processes and is considered a key reversible... more Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD)(+) level-dependent, we show that NAD(+) is orchestrated by both feeding rhythms and the circadian clock through the NAD(+) ...

Proteomics. Clinical applications, Jan 29, 2017

The nutritional intervention program "DiOGenes" focuses on how obesity can be prevented... more The nutritional intervention program "DiOGenes" focuses on how obesity can be prevented and treated from a dietary perspective. We generated differential plasma proteome profiles in the DiOGenes cohort to identify proteins associated with weight loss and maintenance and explore their relation to body mass index, fat mass, insulin resistance and sensitivity. Relative protein quantification was obtained at baseline and after combined weight loss/maintenance phases using isobaric tagging and MS/MS. A Welch t-test determined proteins differentially present after intervention. Protein relationships with clinical variables were explored using univariate linear models, considering collection center, gender and age as confounding factors. 473 subjects were measured at baseline and end of the intervention; 39 proteins were longitudinally differential. Proteins with largest changes were sex hormone-binding globulin, adiponectin, C-reactive protein, calprotectin, serum amyloid A, and...

Scientific Reports

Holistic human proteome maps are expected to complement comprehensive profile assessment of healt... more Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes. However, methodologies to analyze proteomes in human tissue or body fluid samples at relevant scale and performance are still limited in clinical research. Their deployment and demonstration in large enough human populations are even sparser. In the present study, we have characterized and compared the plasma proteomes of two large independent cohorts of obese and overweight individuals using shotgun mass spectrometry (MS)-based proteomics. Herein, we showed, in both populations from different continents of about 500 individuals each, the concordance of plasma protein MS measurements in terms of variability, gender-specificity, and age-relationship. Additionally, we replicated several known and new associations between proteins, clinical and molecular variables, such as insulin and glucose concentrations. In conclusion, our MS-based analyses of plasma samples from independent human cohorts proved the practical feasibility and efficiency of a large and unified discovery/replication approach in proteomics, which was also recently coined "rectangular" design. In the very recent years, technology improvements have induced an important paradigm shift for biomarker discovery in plasma (as well as in other body fluids and tissues) using mass spectrometry (MS)-based proteomics. Moving from a "triangular" to a "rectangular" approach 1 , we and others have been innovating the clinical proteomic discovery study design from limited sample sizes to much larger cohorts of individuals 2-5. Common proteomic strategies have applied a "triangular" or funnel design where initial discoveries are obtained on few samples (typically tens), followed by replication and validation of biomarker candidates on increasing numbers of samples (from typically hundreds to thousands). While technical constraints in sample preparation, liquid chromatography (LC) tandem MS (MS/MS) analysis, and bioinformatics have shaped such strategies, new developments in all those areas allow today deeper proteome coverage with higher throughput, offering new possibilities to design proteomic studies. Larger cohorts of human biospecimens (from typically hundreds to thousands) can now be studied with measurements of several hundreds to a thousand of proteins in plasma for instance. In a review, Geyer et al. recently used the "rectangular" adjective to conceptualize a clinical study design where both proteomic discovery and validation are performed similarly and on the same large enough number of samples and protein analytes 1. Practical demonstration of such a concept is however still lacking. Here, we present one of the first examples of such analyses of two large independent cohorts using MS-based proteomics.

Modification strategies targeting specific amino acids in proteins are widespread in proteomic an... more Modification strategies targeting specific amino acids in proteins are widespread in proteomic analysis. Cysteine residues have received deep consideration in view of their nucleophilic properties and their occurrence in the proteome. A recently developed micro-electrospray emitter for mass spectrometry was used to electrogenerate species reactive towards specific residues in biomolecules. When spraying L-cysteine in the presence of hydroquinone, the thiol cysteine moiety reacts via a 1,4-Michael addition with the benzoquinone electrochemically generated at the electrode. A series of electrogenerated selective electrophiles based on substituted benzoquinones was characterized as tags for L-cysteine. The rate constants pertaining to the addition of L-cysteine onto the benzoquinones were determined through electrochemical techniques. It was shown that the rate constants are primarily dependent on the electronic nature of the substituents. The apparent tagging extents observed for L-cy...

EuPA Open Proteomics, 2013

Blood Biomarker Diagnosis Liquid chromatography Mass spectrometry Shotgun proteomics a b s t r a ... more Blood Biomarker Diagnosis Liquid chromatography Mass spectrometry Shotgun proteomics a b s t r a c t In this study, several workflows to analyze human plasma proteins with RP-LC MS/MS are evaluated. The impact of depletion of abundant proteins on the plasma proteome coverage was assessed together with the duration of RP-LC separation. An additional upstream liquidbased fractionation was evaluated. The applicability and feasibility of these technologies in large-scale clinical studies with respect to effort, throughput, and outcome are discussed.