A5072176046- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Natural product bioactivities and synthesis
- Viral gastroenteritis research and epidemiology
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- Hippo pathway signaling and YAP/TAZ
- Monoclonal and Polyclonal Antibodies Research
- Malaria Research and Control
- Cancer-related gene regulation
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- interferon and immune responses
- Liver Disease Diagnosis and Treatment
- Traditional and Medicinal Uses of Annonaceae
- Viral Infections and Immunology Research
- Pharmacological Receptor Mechanisms and Effects
- Mast cells and histamine
- Phytochemistry and Biological Activities
- Cancer, Hypoxia, and Metabolism
- Plant biochemistry and biosynthesis
- Pancreatic function and diabetes
- Advanced Proteomics Techniques and Applications
Sanofi (France)
2002-2023
Architecture et Fonction des Macromolécules Biologiques
2014-2023
Centre National de la Recherche Scientifique
2010-2022
Aix-Marseille Université
2001-2022
Bioénergétique et Ingénierie des Protéines
1994-2015
University of New Caledonia
2012
Institut du Cerveau
2003
Inserm
1992-2002
Institut Claudius Regaud
2002
Délégation Provence et Corse
2001
Abstract The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). recently entered phase III clinical trials for the treatment of COVID-19. Once in cells, is converted into its triphosphate form, AT-9010, that presumably targets viral RNA-dependent RNA polymerase (RdRp, nsp12), incorporation RNA. Here we report 2.98 Å cryo-EM structure SARS-CoV-2 nsp12-nsp7-nsp8 -RNA complex, showing AT-9010 bound at three sites...
A midthroughput screening follow-up program targeting the first bromodomain of human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with affinity in low micromolar range yet exerts suitable unexpected selectivity vitro against other members and extra-terminal domain (BET) family. structure-based pinpointed a role ZA loop, paving way for development potent selective BET-BRDi probes.
White adipose tissue (WAT) expands in part through adipogenesis, a process involving fat cell generation and fatty acid (FA) storage into triglycerides (TGs). Several findings suggest that inter-individual regional variations adipogenesis are linked to metabolic complications. We aimed identify cellular markers define human adipocyte progenitors (APs) with pronounced adipogenic/TG ability. Using an unbiased single screen of passaged adipose-derived stromal cells (hADSCs), we identified...
Abstract Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization which remains to be defined. Here we report that lobules are composed two extracellular matrix compartments, i.e., septa and stroma, delineating niches CD45−/CD34+/CD31− progenitor subsets characterized by MSCA1 (ALPL) CD271 (NGFR) expression. MSCA1+ adipogenic subset enriched in stroma while contains mainly MSCA1−/CD271− MSCA1−/CD271 high progenitors. marks myofibroblast precursors NGF...
Here, we have used patient-derived induced pluripotent stem cell (iPSC) and gene-editing technology to study the cardiac-related molecular functional consequences of mutations in GLA causing lysosomal storage disorder Fabry disease (FD), for which heart dysfunction is a major cause mortality. Our vitro model recapitulated clinical data with FD cardiomyocytes accumulating GL-3 displaying an increased excitability, altered electrophysiology calcium handling. Quantitative proteomics enabled...
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic inflammatory disease often accompanied by impairment of sense smell. This symptom has been somewhat overlooked, and its relationship to cytokines, tissue compression, neuronal loss, neurogenesis still unclear.In order elucidate potential mechanisms leading CRS in humans, we have established type 2/T helper 2 cell (Th2)-mediated allergic mouse model, based on house dust mite (HDM) Staphylococcus aureus enterotoxin B (SEB)...
The Wiskott‐Aldrich syndrome (WAS) is a rare immunodeficiency disease affecting mainly platelets and lymphocytes. Here, we show that the WAS gene product, WASp, tyrosine phosphorylated upon aggregation of high affinity IgE receptor (FcϵRI) at surface RBL‐2H3 rat tumor mast cells. Lyn Bruton's kinase (Btk), two protein kinases involved in FcϵRI‐signaling phosphorylate WASp interact with vivo. Interestingly, expression GTPase defective mutant form CDC42, interacts accompanied by substantial...
An in vitro screening of New Caledonian plants allowed the selection several species with a significant dengue virus NS5 RNA-dependent RNA polymerase (RdRp) inhibiting activity. The chemical investigation Cryptocarya chartacea led to isolation series new mono- and dialkylated flavanones named chartaceones A-F (1-6), along pinocembrin. They were isolated as racemic mixtures characterized using extensive one- two-dimensional NMR spectroscopy. Four diastereomers chartaceone A (1) separated...
In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts madagascan plants was performed in virus-cell-based assay for CHIKV, DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark Flacourtia ramontchi selected its significant activity both assays. Six new phenolic glycosides, named flacourtosides A–F (1–6), glycosides itoside H, xylosmin, scolochinenoside D,...
Toll-like receptor–mediated responses to pathogens can be modulated by targeting the TLR co-receptor CD14.
Accumulation of neurofilaments (NFs), the major constituents neuronal cytoskeleton, is a distinctive feature neurological diseases and several studies have shown that soluble NFs can be detected in cerebrospinal fluid (CSF) patients with diseases, such as multiple sclerosis frontotemporal dementia. Here we used an inducible transgenic mouse model neurodegeneration, CamKII-TetOp25 mice, to evaluate whether NF-L levels CSF or blood biochemical biomarker neurodegeneration. Induction p25...
Amino acid sequencing of peptides obtained after proteolytic hydrolysis Aspergillus flavus urate oxidase (uricase) permitted the design oligodeoxynucleotide probes that were used to obtain 1.2-and 5-kilobase pair DNA fragments from A. cDNA and genomic libraries, respectively.The fragment contained entire coding region for uricase, comparison with revealed presence two short introns in gene.A. uricase has around 40% overall identity uricases higher organisms but many conserved amino...