PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1–p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells

Prise en charge de patients à problématique addictive admis au service d'accueil des urgences psychiatriques du C[entre] H[ospitalier] Le Vinatier à Lyon et orientés en consultation externe d'addictologie de liaison

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Peut-on réduire le nombre d'anesthésies générales en coloscopie ? (comparaison des coloscopies sous anesthésie générale et sous sédation vigile par voie orale et revue de la littérature)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

LES VARICES OESOPHAGIENNES A LA PHASE HEMORRAGIQUE ET EN PROPHYLAXIE SECONDAIRE (ANALYSE COMPARATIVE DES METHODES ENDOSCOPIQUES)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Locally refined discrete velocity grids for stationary rarefied flow simulations

Most of deterministic solvers for rarefied gas dynamics use discrete velocity (or discrete ordinate) approximations of the distribution function on a Cartesian grid. This grid must be sufficiently large and fine to describe the distribution functions at every space position in the computational domain. For 3-dimensional hypersonic flows, like in re-entry problems, this induces much too dense velocity grids that cannot be practically used, for memory storage requirements. In this article, we present an approach to generate automatically a locally refined velocity grid adapted to a given simulation. This grid contains much less points than a standard Cartesian grid and allows us to make realistic 3-dimensional simulations at a reduced cost, with a comparable accuracy

Metabolic consequences of various fruit-based diets in a generalist insect species

All data & code generated during this study have been deposited in the INRAE dataverse: https://entrepot.recherche.data.gouv.fr/dataset.xhtml?persistentId=doi:10.57745/G4D3PG. The shiny application enabling the exploration and analysis of our complete dataset (PCA, GLM/Elastic Net and associated visualizations) is available here: https://fruitfliesmetabo.shinyapps.io/shiny.International audienceMost phytophagous insect species exhibit a limited diet breadth and specialize on a few or a single host plant. In contrast, some species display a remarkably large diet breadth, with host plants spanning several families and many species. It is unclear, however, whether this phylogenetic generalism is supported by a generic metabolic use of common host chemical compounds ('metabolic generalism') or alternatively by distinct uses of diet-specific compounds ('multi-host metabolic specialism')? Here, we simultaneously investigated the metabolomes of fruit diets and of individuals of a generalist phytophagous species, Drosophila suzukii, that developed on them. The direct comparison of metabolomes of diets and consumers enabled us to disentangle the metabolic fate of common and rarer dietary compounds. We showed that the consumption of biochemically dissimilar diets resulted in a canalized, generic response from generalist individuals, consistent with the metabolic generalism hypothesis. We also showed that many diet-specific metabolites, such as those related to the particular color, odor, or taste of diets, were not metabolized, and rather accumulated in consumer individuals, even when probably detrimental to fitness. As a result, while individuals were mostly similar across diets, the detection of their particular diet was straightforward. Our study thus supports the view that dietary generalism may emerge from a passive, opportunistic use of various resources, contrary to more widespread views of an active role of adaptation in this process. Such a passive stance towards dietary chemicals, probably costly in the short term, might favor the later evolution of new diet specializations