Production des protéines thérapeutiques par génie génétique (intérêts du système végétal)

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

The mycotoxins deoxynivalenol and nivalenol show in vivo synergism on jejunum enterocytes apoptosis

Remerciements : Plate-forme CIRE Chirurgie et Imagerie pour la Recherche et l’Enseignement, INRA, UMR PRC 37380 Nouzilly, Centre Val de LoireThe mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for human and animal gut health, following exposure through contaminated food and feed. The aim of this work was to analyze the effects of DON and NIV, alone or associated, on the intestinal pig mucosa. Jejunal loops were used for testing DON and NIV individually and in combination (1:1) after a single exposure, for 24 hours. For repeated exposure, piglets received a natural contaminated feed, with DON or with DON+NIV for 28 days. Histological investigations, proliferation and apoptosis assessments were conducted. Both experiments were concordant for the total-cell proliferation decreased at the villus tips after DON or DON+NIV at 10 μM acutely, or repeatedly, by 30-35% and 20-25%, respectively. In loops model, apoptotic enterocytes at villus tips increased dose-dependently after DON, NIV alone or DON+NIV in combination. The combination in loops at 10 μM showed higher effects on proliferation and apoptosis than DON alone, and synergism was shown for villus apoptotic enterocyte. These results are to be considered for NIV consumer risk assessment. Our results demonstrate the in vivo disruption of the intestinal balance proliferation/apoptosis explaining, at least partly, the disruption of intestinal barrier by these mycotoxins

Effects of Chronic Ingestion of Deoxynivalenol and 15 Acetyldeoxynivalenol in the Liver of Piglets

International audienc

The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: Interest of ex vivo models as an alternative to in vivo experiments

AbstractTrichothecenes induce changes in the intestinal barrier function through decreased expression of cell junction proteins and apoptosis of enterocytes. The mitogen activated protein kinases (MAPK) play an important role in the signaling pathways of cell turnover and differentiation. Using ex vivo and in vivo approaches, the purpose of this study was to investigate the ability of low doses of DON to induce histological changes in the intestine and to activate the MAPK ERK 1/2, p38 and JNK. Twelve weaning piglets received during four weeks a control diet or a DON-contaminated diet (2.3 mg DON/kg feed). Six weaning piglets were used to prepare jejunal explants (ex vivo model). Explants were exposed during 4 h to vehicle, 5 or 10 μM DON. Intestinal changes were graded using a histological score. Pigs fed a DON-diet and explants exposed to DON showed a significant decrease in the jejunal score. In both models, the toxin significantly enhanced phosphorylation of ERK 1/2 and p38, whereas the increased phosphorylation of JNK was non significant. Taken together these results indicate that in vivo or ex vivo exposure of intestinal tissue to DON lead to similar intestinal lesions and activation of MAPK. These effects could impair the homeostasis of intestinal tissue in the aspects of barrier function and immune protection. The similarity of the in vivo and ex vivo results provides also strong evidence that the jejunal explant model is a good alternative for toxicological studies in intestinal tissue

Toxicity of Deoxynivalenol and Its Acetylated Derivatives on the Intestine: Differential Effects on Morphology, Barrier Function, Tight Junction Proteins, and Mitogen-Activated Protein Kinases

International audienceThe intestinal epithelium is the first barrier against food contaminants and is highly sensitive to mycotoxins, especially de oxynivalenol (DON). Consumption of DON-contaminated food is associated with outbreaks of gastroenteritis. In cereals and their byproducts, DON is present together with two acetylated derivatives, 3-ADON and 15-ADON. The aim of this study was to compare the intestinal toxicity of DON and A-DONs, using noncytotoxic doses. The toxicity was assessed using in vitro (intestinal epithelial cell line), ex vivo (intestinal explants), and in vivo (animals exposed to mycotoxin-contaminated diets) models. The effects were studied on cell proliferation, barrier function, and intestinal structure. The mechanism of toxicity was investigated by measuring the expression of the tight junction proteins and of phosphorylated ERK1/2, p38, and JNK, which are effectors of signaling pathway involved in cellular programs including embryogenesis, proliferation, differentiation, and apoptosis. On proliferating cells, 3-ADON was less toxic than DON, which was less toxic than 15-ADON. On differentiated cells, 15 similar to ADON impaired the barrier function, whereas DON and 3 similar to ADON did not have a significant effect. Similarly, ex vivo and in vivo, 15-ADON caused more histological lesions than DON or 3-ADON. At the molecular level, the 15 similar to ADON activated the mitogen-activated protein kinases (MAPK) ERK1/2, p38, and JNK in the intestinal cell line, explants, and the jejunum from exposed animals at lower dose than DON and 3-ADON. Our results show that the higher toxicity of 15-DON is due to its ability to activate the MAPK. Given that cereal-based foods are contaminated with DON and acetylated-DON, the higher toxicity of 15-ADON should be taken into account

L’Éloge du Prince

S’interrogeant sur une pratique à la fois littéraire et politique, les auteurs de cet ouvrage ont envisagé les différentes facettes de l’éloge adressé à un Prince, qu’il s’agisse d’un empereur romain ou d’un roi de France. Sont ainsi proposées, pour une période qui va de l’Antiquité au temps des Lumières, des réflexions sur les aspects théoriques du genre épidictique et ses textes fondateurs, ainsi que des synthèses sur le fonctionnement de l’éloge, sa pratique et son rôle dans la cité. Un fil directeur unit ces approches diverses : l’intérêt pour un fait politique et littéraire intemporel mais changeant, qui ouvre la voie à des interrogations sur la force de la rhétorique

Bibliothèques d’écrivains

Espace de travail, de loisir ou d’évasion, la bibliothèque remplit toutes sortes de fonctions pour un écrivain. Elle est un patrimoine matériel qui se construit, se transmet et se disperse, mais aussi un atelier où les lectures, savantes ou sauvages, viennent nourrir la création; enfin elle constitue le lieu d’un réseau de savoirs où se découvrent des filiations, des circulations et des dialogues parfois insoupçonnés. Telles sont les trois facettes des bibliothèques d’écrivains explorées dans ce volume, pour des auteurs de l’époque médiévale à l’époque contemporaine qui ont voyagé en Europe, Amérique et Asie. Ces études interrogent les archives papier ou numériques de figures intellectuelles variées: poètes, linguistes, philosophes, cinéastes ou critiques. Issu d’un séminaire du laboratoire Lexiques, Textes, Discours, Dictionnaires (LT2D) de l’Université de Cergy-Pontoise et d’un colloque co-organisé avec la Bibliothèque nationale de France en 2014, cet ouvrage bénéficie du soutien de la Fondation des Sciences du Patrimoine