Le rôle de LATS1 et de LATS2 dans le développement du cortex surrénalien

La voie de signalisation Hippo est une cascade de kinases hautement conservée entre les espèces qui contrôle des processus cellulaires fondamentaux comme la prolifération, l’apoptose et la différenciation. Dans la cascade, les kinases Large tumor suppressor 1 et 2 (LATS1/2) phosphorylent et inactivent les co-activateurs transcriptionnels Yes-associated protein (YAP) et Transcriptional coactivator with PDZ-binding motif (TAZ) pour réguler finement le développement, la taille et l’homéostasie de nombreux tissus. Bien qu’il ait été démontré que YAP/TAZ étaient essentiels au maintien du cortex surrénalien durant la vie adulte, le rôle des kinases en amont n’a jamais été étudié. L’objectif de ce projet était donc d’élucider le rôle de LATS1 et de LATS2 dans le développement corticosurrénalien. Pour ce faire, un modèle de souris Lats1flox/flox;Lats2flox/flox;Nr5a1-cre, permettant l’inactivation conditionnelle de Lats1/2 dans les tissus stéroïdiens, a été créé. La caractérisation de ce modèle a révélé que Lats1/2 étaient indispensables pour maintenir l’identité des cellules adrénocorticales durant le développement embryonnaire. En l’absence de Lats1/2, les cellules du cortex acquièrent des propriétés myofibroblastiques et perdent progressivement leur capacité de stéroïdogenèse, causant une insuffisance surrénalienne fatale vers 2 à 3 semaines d’âge chez les deux sexes. Cette transdifférenciation est probablement causée, du moins en partie, par une augmentation de l’activité transcriptionnelle de YAP/TAZ puisqu’une augmentation de l’expression nucléaire de YAP/TAZ et de l’expression de certains gènes cibles de la voie Hippo ont été observées dans les cellules myofibroblastiques. Ces résultats révèlent donc un tout nouveau rôle de la voie Hippo dans le développement du cortex surrénalien.The Hippo signaling pathway is a highly conserved kinase cascade that controls fundamental cellular processes such as proliferation, apoptosis and differentiation. In this cascade, the Large tumor suppressor kinase 1 and 2 (LATS1/2) phosphorylate and inactivate the main downstream effectors, Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ), to finely regulate the development, size and homeostasis of several organs. It was recently demonstrated that YAP and TAZ were essential for the maintenance of the adrenal cortex during adult life, but the role of the upstream kinases has never been studied. The objective of the present project was therefore to elucidate the role of LATS1 and LATS2 in adrenocortical development. We generated a Lats1flox/flox;Lats2flox/flox;Nr5a1-cre mouse model in which Lats1/2 were conditionally inactivated in steroidogenic cells. The characterization of this model revealed that Lats1/2 were required to maintain proper adrenocortical cell identity during embryonic development. In the absence of Lats1/2, adrenocortical cells acquire myofibroblastic properties and lose their steroidogenic capacity, leading to adrenal deficiency and death at 2 to 3 weeks of age. This transdifferentiation is probably caused, at least in part, by an increased transcriptional activity of YAP/TAZ since a stronger nuclear expression of YAP/YAZ and higher expression levels of Hippo target genes were observed in the myofibroblastic population. These results suggest an important novel role of Hippo signaling in adrenal cortex development

Transitions - note 10

Note complète ; Résumé ; Capsule: Ingénieure ou infirmier: les choix traditionnels et non traditionnels des filles et des garçons

Static in vitro digestion models for term infants : review of the literature

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A cidade asilo: crimes de guerra e crimes sociais

Resenha a SHOHAM, Liad. Asylum city: a novel. Trans. Sara Kitai. New York: Harper, 2014

Impact des procédés de transformation sur la digestion du lait maternel et des formules infantiles par le nouveau-né.

Ce numéro est constitué d’articles issus du colloque « Alimentation périnatale, alimentation des séniors: spécificités, impact du microbiote », organisé le 28 mars 2018 à Paris.Despite the efforts made over the last decades to bring the composition of infant formulas closer to thatof human milk, important differences in composition and structure of the constituents remain betweenthese two foods. The human milk, true "gold standard" for the feeding of the newborn, has nativestructures (casein micelle, fat globule) which are modified by the technological treatments used in themanufacture of infant formulas. These changes result in behavioral differences between the twoproducts in the digestive tract of the newborn (faster gastric emptying for human milk, differences inkinetics of hydrolysis of proteins and lipids). The heat treatments used in the production of formulas leadto the denaturation and aggregation of milk proteins affecting their resistance to the action of digestiveenzymes. Caseins become more resistant to hydrolysis while serum proteins are more sensitive tohydrolysis. Homogenization transforms the fat globule of milk of several microns of diameter into submicronlipid droplets and thus increases the specific surface area available for gastric lipase leading toan acceleration of lipolysis. The physiological consequences for the newborn remain to be establishedbut preliminary work shows that these changes affect the maturation of the immune system and thestructuring of the intestinal microbiota.Malgré les efforts réalisés ces dernières décennies pour rapprocher la composition des formulesinfantiles de celle du lait humain, d’importantes différences de composition et de structure desconstituants demeurent entre ces deux aliments. Le lait humain, véritable « gold standard » pourl’alimentation du nouveau-né présente des structures natives (micelle de caséines, globule gras) quisont modifiées par les traitements technologiques utilisés lors de la fabrication des formules infantiles.Ces modifications se traduisent par des différences de comportement entre les deux produits dans letube digestif du nouveau-né (vidange gastrique plus rapide pour le lait humain, cinétiques d’hydrolysedes protéines et des lipides différentes). Les traitements thermiques utilisés lors de la fabrication desformules infantiles entrainent la dénaturation et l’agrégation des protéines laitières affectant leurrésistance à l’action des enzymes digestives. Les caséines deviennent plus résistantes à l’hydrolysetandis que les protéines sériques y sont plus sensibles. L’homogénéisation transforme le globule grasdu lait de plusieurs microns de diamètre en petites gouttelettes lipidiques sub-microniques et augmenteainsi la surface spécifique disponible pour la lipase gastrique entrainant une accélération de la lipolyse.Les conséquences physiologiques pour le nouveau-né restent à établir mais des travaux préliminairesmontrent que ces modifications affectent la maturation du système immunitaire et la structuration dumicrobiote intestinal

Evaluation of current dosing guidance for oral rifampicin treatment in adult patients with osteoarticular infections

International audienceFor management of osteoarticular infections, rifampicin appears to be the key antibiotic. We aimed to evaluate the actual rifampicin dosing regimens using a population pharmacokinetic model of rifampicin in patients with osteoarticular infections. A Monte Carlo simulation study was performed to simulate steady-state plasma concentrations for 1000 randomly sampled subjects using a total daily dose between 600 and 1200 mg (600 and 900 mg once daily, 450 and 600 mg twice daily, or 300 mg 3 times daily). When rifampicin was administered with fusidic acid, the pharmacokinetic/pharmacodynamic (PK/PD) target (area under the curve/minimum inhibitory concentration ≥952) was achieved with all tested dosing regimen, except 600 mg once daily for Staphylococcus epidermidis infections. Without coadministration of fusidic acid, none of tested dosing regimens achieved this PK/PD target. Most recommended drug-dosing regimens allow attaining the fixed area under the curve/minimum inhibitory concentration target for Staphylococcus aureus and coagulase-negative staphylococcal osteoarticular infections. In future studies, PK/PD target for osteoarticular infections in human should also be confirmed

Recognition of Handwritten Script by Using Neural Network

Abstract- India is a multi script and multilingual country where a varity of different scripts is used in writing documents. It is important to know a script used in writing. Script recognitions have many important applications like automatic transcription of multilingual documents, searching document image, script sorting. Proposed work emphasis on the “block level technique ” which is conquered with manual which compromises Training, Calculating Error and Modifying Weights. A problem where script recognition recognizes the encountered with a 20x 20 matrix is time-consuming training compression and script of the given document in a mixture of various script documents. Feature extraction technique is an important step in Script recognition. In this project, we have used combined approach of Discrete Cosine Transform (DCT) and discrete wavelets Transform (DWT) for feature extraction and neural network(feedforward back propagation) classifier for classification and recognition purpose. Keywords:- Multi-script documents, Handwritten scripts, Discrete cosine Transform, Discrete wavelets transform, neural network I

Obsidian value and exchange in the southern Red Sea region and its role in the establishment of prehistoric complex society: new data from South Arabia and the African Horn

International audienceThe Red Sea is renowned as a locus of maritime activity during the early historic periods. As a resultof systematic obsidian analyses of sources and artifacts, maritime interaction in South Arabia can now be traced back to the beginning of the Neolithic period. Its increased intensity is echoed in the cultural sphere that eventually formed on opposing shores of the two continents by at least the third millennium B.C. New geochemical, archaeological, and technological data from South Arabia, Ethiopia and Djibouti illustrate the current state of research on Afro-Arabian prehistoric interactions, highlighting variabilities and relationships between two mirroring regions either bound or separated by the Red Sea. While major chronological gaps remain regarding the transition from the LSA to the Neolithic, the study of lithic and faunal material from several sites allows us to note major technological and subsistence shifts that occurred independently in each region, but also early links,such as maritime interaction, that may have affected the nature of the process of neolithization. Finally, we discuss obsidian circulation in light of elements of cultural convergence that make up theRed Sea cultural sphere and that occur sometime in the late 4th millennium B.C