Single cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations

peer reviewedAlzheimer's disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex-dependence for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changes shared across multiple cell types and cell type-specific changes were observed. The differential genes showed significant over-representation of known AD-relevant processes, such as pathways associated with neuronal differentiation, programmed cell death and inflammatory responses. Regulatory network analysis of these genes revealed upstream regulators that modulate many of the downstream targets with sex-dependent changes. Most key regulators have been previously implicated in AD, such as Egr1, Klf4, Chchd2, complement system genes, and myelin-associated glycoproteins. Comparing with similar data from the Tg2576 AD mouse model and human AD patients, we identified multiple genes with consistent, cell type-specific and sex-dependent alterations across all three datasets. These shared changes were particularly evident in the expression of myelin-associated genes such as Mbp and Plp1 in oligodendrocytes. In summary, we observed significant cell type-specific transcriptomic changes in the THY-Tau22 mouse model, with a strong over-representation of known AD-associated genes and processes. These include both sex-neutral and sex-specific patterns, characterized by consistent shifts in upstream master regulators and downstream target genes. Collectively, these findings provide insights into mechanisms influencing sex-specific susceptibility to AD and reveal key regulatory proteins that could be targeted for developing treatments addressing sex-dependent AD pathology.Validating Digital Biomarkers For Better Personalized Treatment Of Parkinson's Disease3. Good health and well-bein

Application des dosages par immunoéphélémétrie microparticulaire des caséines alpha, beta et kappa à l'évaluation de la qualité du lait, de sa production à sa valorisation fromagère

National audienc

Réseau PRO : Création d'un réseau d'essais au champ et d'un outil de mutualisation des données pour l'étude de la valeur agronomique et des impacts environnementaux des Produits Résiduaires Organiques recyclés enagriculture

Ce 49ème volume de la Revue Innovations Agronomiques regroupe l'ensemble de la restitution des projets Casdar, présentés le 3 novembre 2015.The "PRO Network” project (2011-2014) has enabled the creation of a national network of trials investigating the effects of agricultural organic waste products (PRO) applications in very different agropedo-climatic situations and for a range of applied PRO. This network was firstly, to harmonize the methods of study and follow-up effects of PRO applied to the field, and secondly to pool data acquired on a wide range of field trials. Have thus been developed: an inventory of 437 tests of PRO in France, an operational methodological guide of field test on the PRO, a method of referencing of the PRO with a first draft of nomenclature, and an information system shared by PRO network and the PRO SOERE. Collected data led to improve the setting of the tools developed within the RMT fertilization & environment (Tools for environmental diagnosis and management of fertilization and the Organic Statute of the soil). Finally, the critical analysis of pooled data sets resulted in recommendations for future trials.Le projet « Réseau PRO » (2011-2014) a permis la constitution d’un réseau national d’essais étudiant les effets des épandages agricoles de produits résiduaires organiques (PRO) dans des situations agropédo-climatiques très différentes et pour une grande diversité de PRO épandus. Ce réseau visait d’une part, à harmoniser les méthodes d’étude et de suivi des effets des PRO épandus au champ, et d’autre part à mutualiser les données acquises sur une grande diversité d’essais au champ. Ont ainsi été élaborés : un inventaire de 437 essais étudiant les PRO en France, un guide méthodologique opérationnel de conduite d’essai de plein champ sur les PRO, une méthode de référencement des PRO et une première ébauche de nomenclature, et un système d’information commun au Réseau PRO et au SOERE PRO. Par ailleurs, les données recueillies ont permis d’améliorer le paramétrage des outils développés au sein du RMT Fertilisation & Environnement (outils de diagnostic environnemental et de gestion de la fertilisation et du statut organique des sols). Enfin, l’analyse critique des jeux de données mutualisés a donné lieu à des recommandations pour les futurs essais

Agro-éco-Syst'N : Identification de systèmes agroécologiques à hautes performances azotées par le diagnostic avec l'outil Syst'N ®

International audienceLe projet Agro-éco-Syst’Nvisait à doter les conseillers agricoles, formateurs et enseignants de méthodes, outils et références leur permettant d’identifier et de concevoir des systèmes de culture à faibles pertes azotées vers l’environnement. A cette fin, une méthode de diagnostic des pertes d’azote vers l’eau (par lixiviation) et vers l’air (par volatilisation), utilisant l’outil Syst’N®, a été élaborée et formalisée. Elle a ensuite été utilisée pour évaluer et expliquer les performances azotées de plusieurs systèmes de culture dans des contextes pédoclimatiques variés.Quinze systèmes de culture ont ainsi été évalués et diagnostiqués. Leur analyse transversale a montré comment différentes combinaisons de pratiques dans un contexte donné conduisent à des performances variables en matière de pertes d’azote. Enfin, 21 cas-types ont été mis à disposition pour outiller les enseignants et conseillers sur le diagnostic des pertes d’azote, ressources mobilisables dans un éventail d’objectifs pédagogiques, de l’évaluation des pertes azotées à la reconception de systèmes de culture. Les systèmes simulés avec Syst’N®sont diffusés viala base de données Pertazote, mise à niveau au cours du proje

One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals

International audienceBackground: Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile.Methods: The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping.Results: In total, 721 patients were included in this study. The median age was 73 years (range 18-101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection.Conclusion: Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains