A rhenium tris-carbonyl derivative as a single core multimodal probe for imaging (SCoMPI) combining infrared and luminescent properties.

International audienceA rhenium tris-carbonyl derivative has been designed to couple infrared and luminescent detection in cells. Both spectroscopies are consistent with one another; they point out the reliability of the present SCoMPI (for Single Core Multimodal Probe for Imaging) for bimodal imaging and unambiguously indicate a localization at the Golgi apparatus in MDA-MB-231 breast cancer cells

Properties, mechanism and applications of diamond as an antibacterial material

Antibiotic resistance in bacteria is a current threat causing an increasing number of infections of difficult clinical management. While the overuse and misuse of antibiotics are investigated to reduce them, the need for alternatives to approaches is rising. Carbon-based materials shown recent moderate to high antibacterial properties and diamond, thanks to its superior mechanical, tribological, electrical, chemical and biological quality is a choice material to investigate for safe antibacterial films, coatings and particles. Here, the antibacterial properties of diamond films, nanodiamonds, DLC films and a comprehensive list of the composites developed from them are discussed along with a summary of the bacterial strains used and the most efficient composition and/or concentration discovered. In a later stage, the mechanisms of action and the parameters that are believed to influence them are discussed and finally, an overview of the biomedical and food industry applications is given

Urban Climate, Human behavior & Energy consumption: from LCZ mapping to simulation and urban planning (the MapUCE project)

International audienceThe MApUCE project aims to integrate in urban policies and most relevant legal documents quantitative data from urban microclimate, climate and energy.The primary objective of this project is to obtain climate and energy quantitative data from numerical simulations, focusing on urban microclimate and building energy consumption in the residential and service sectors, which represents in France 41% of the final energy consumption. Both aspects are coupled as building energy consumption is highly meteorologically dependent (e.g. domestic heating, air-conditioning) and heat waste impact the Urban Heat Island. We propose to develop, using national databases, a generic and automated method for generating Local Climate Zones (LCZ) for all cities in France, including the urban architectural, geographical and sociological parameters necessary for energy and microclimate simulations.As will be presented, previous projects on adaptation of cities to climate change have shown that human behavior is a very potent level to address energy consumption reduction, as much as urban forms or architectural technologies. Therefore, in order to further refine the coupled urban climate and energy consumption calculations, we will develop within TEB (and its Building Energy Module) a model of energy consumer behavior.The second objective of the project is to propose a methodology to integrate quantitative data in urban policies. Lawyers analyze the potential levers in legal and planning documents. A few “best cases” are also studied, in order to evaluate their performances. Finally, based on urban planning agencies requirements, we will define vectors to include quantified energy-climate data to legal urban planning documents. These vectors have to be understandable by urban planners and contain the relevant information.To meet these challenges, the project is organized around strongly interdisciplinary partners in the following fields: law, urban climate, building energetics, architecture, sociology, geography and meteorology, as well as the national federation of urban planning agencies.In terms of results, the cross-analysis of input urban parameters and urban micro-climate-energy simulated data will be available on-line as standardized maps for each of the studied cities. The urban parameter production tool as well as the models will be available as open-source. LCZ and associated urban (and social!) indicators may be integrated within the WUDAPT database

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

11 páginas, 4 figuras, 2 tablas. Datasets en su material suplementario. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2302720120/-/DCSupplemental.Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.This work was supported by the Michael J. Fox Foundation grant MJFF-020161 (E.M., Z.G.-O.), NIH and National Institute of Aging grants AG060747 (M.D.G.), AG066206 (Z.H.), AG066515 (Z.H., M.D.G.), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, Y.L.G.), the Alzheimer’s Association (AARF-20-683984, M.E.B.), and the Iqbal Farrukh and Asad Jamal Fund, a grant from the EU Joint Programme—Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB; JPND), the Japan Agency for Medical Research and Development JP21dk0207045 (T.I.), JP21dk020704 (K.O., S.N.), JP21km040550 (K.O.), the Einstein Center for Neurosciences in Berlin (S.M.Y.), the Swedish Research Council (#2018-02532, H.Z.), the European Research Council (#681712, H.Z.), and the Swedish State Support for Clinical Research (#ALFGBG-720931, H.Z.). Inserm UMR1167 is also funded by the Inserm, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine, and the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Additional funders of individual investigators and institutions who contributed to data collection and genotyping are provided in SI Appendix.Peer reviewe

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

The diversity of rational patterns in microeconomics

La microéconomie conventionnelle présente le concept de rationalité de manière univoque et étroite comme maximisation de l'utilité espérée. On sait les critiques qui ont été adressées à ce concept tant du point de vue de l'économie comportementale que de celui de la sociologie. Notre objectif est de proposer une lecture de certaines de ces critiques afin de montrer que, pour l'essentiel, elles mettent en évidence la diversité des modes de rationalité. Le problème est, dès lors, de savoir si le constat de cette diversité conduit nécessairement à la récusation du modèle standard. Cette thèse s'inscrit dans la double perspective de la théorie du choix rationnel et de la théorie des jeux. À partir des critiques de l'économie comportementale, nous soutenons que le principe de maximisation constitue un mode de raisonnement local et évaluable au regard du contexte d'action. Mais une telle régionalisation implique une profonde révision de la théorie des jeux standard. La récusation de l'équilibre général, fondé sur le présupposé de la maximisation de l'utilité espérée, comme modèle univoque appelle un nouveau type de formalisation. En ce sens, nous montrons que la modélisation multi-agents permet de penser, de manière contrefactuelle, des interactions entre agents économiques rationnels et situés. Cette méthode nous autorise ainsi à élaborer des scénarios rationalisants qui dessinent des mondes possibles sans trancher entre ces mondes.Standard microeconomics displays the concept of rationality as the maximisation of expected utility i.e. in a narrow and unequivocal sense. The criticisms against this concept made by behavioural economics or sociology are well known. I aim at providing an analysis of some of them in order to emphasise the fact that they mainly highlight the diversity of reasoning modes. But the issue is to know whether the diversity of reasoning modes necessarily leads to reject the standard model. My intention falls into two fields : the theory of Rational Choice and the Game Theory. From the point of view of behavioural economics, I assume that the maximisation is nothing more than a local reasoning mode that can be assessed in relation to the context of action. But this assumption implies correcting the standard Game Theory as well. The fact that the general equilibrium, based on the maximisation of expected utility, cannot be used anymore as an unique model calls a new kind of formalisation. So, I point out that agent-based modelling allows us to conceive, in a counterfactual way, interactions between rational economic agents in their context. Therefore, in this respect, rational patterns of actions and interactions design possible worlds without having to choose between them

ROLE DU PHARMACIEN D'OFFICINE DANS LA PRISE EN CHARGE DES PLAIES (MATERIEL DE PANSEMENT ET PREMIERS SOINS)

CLERMONT FD-BCIU-Santé (631132104) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF