Low-dose pesticide mixture induces senescence in normal mesenchymal stem cells (MSC) and promotes tumorigenic phenotype in premalignant MSC

Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype wasinduced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro andin vivo after cell implantation, in all nude mice. Our results suggest that a commoncombination of pesticides can induce a premature ageing of adult MSC, and as such couldaccelerate age-related diseases. Exposure to pesticide mixture may also promote thetumorigenic transformation in a predisposed stromal environment

Genetic diversity and relationships of the liver fluke Fasciola hepatica (Trematoda) with native and introduced definitive and intermediate hosts

Fasciolosis is a worldwide spread parasitosis mainly caused by the trematode Fasciola hepatica. This disease is particularly important for public health in tropical regions, but it can also affect the economies of many developed countries due to large infections in domestic animals. Although several studies have tried to understand the transmission by studying the prevalence of different host species, only a few have used population genetic approaches to understand the links between domestic and wildlife infections. Here, we present the results of such genetic approach combined with classical parasitological data (prevalence and intensity) by studying domestic and wild definitive hosts from Camargue (southern France) where fasciolosis is considered as a problem. We found 60% of domestic hosts (cattle) infected with F. hepatica but lower values in wild hosts (nutria, 19%; wild boars, 4.5%). We explored nine variable microsatellite loci for 1,148 adult flukes recovered from four different populations (non-treated cattle, treated cattle, nutria and wild boars). Populations from the four groups differed, though we found a number of migrants particularly non-treated cattle and nutria. Overall, we detected 729 different multilocus genotypes (from 783 completely genotyped individuals) and only 46 genotypes repeated across samples. Finally, we experimentally infected native and introduced intermediate snail hosts to explore their compatibility with F. hepatica and assess the risks of fasciolosis expansion in the region. The introduced species Galba truncatula and Pseudosuccinea columella attained the higher values of overall compatibility in relation to the European species. However, concerning the origin, sympatric combinations of G. truncatula were more compatible (higher prevalence, intensity and survival) than the allopatric tested. According to our results, we should note that the assessment of epidemiological risks cannot be limited to a single host–parasite system, but should focus on understanding the diversity of hosts in the heterogeneous environment through space and time.Fil: Vázquez, Antonio A.. Instituto de Medicina Tropical “Pedro Kourí”; Cuba. Université Montpellier II; Francia. Centre National de la Recherche Scientifique; FranciaFil: Sabourin, Emeline. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Alda, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Zoología de Invertebrados I; Argentina. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Leroy, Clémentine. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Leray, Carole. Institut de Recherche de la Tour du Valat; FranciaFil: Carron, Eric. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Mulero, Stephen. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; Francia. Université de Perpignan Via Domitia; FranciaFil: Caty, Céline. Institut de Recherche de la Tour du Valat; FranciaFil: Hasfia, Sarah. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Boisseau, Michel. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Saugné, Lucas. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Pineau, Olivier. Institut de Recherche de la Tour du Valat; FranciaFil: Blanchon, Thomas. Institut de Recherche de la Tour du Valat; FranciaFil: Alba, Annia. Instituto de Medicina Tropical “Pedro Kourí”; Cuba. Università di Corsica Pasquale Paoli; FranciaFil: Faugère, Dominique. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; FranciaFil: Vittecoq, Marion. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; Francia. Institut de Recherche de la Tour du Valat; FranciaFil: Hurtrez Boussès, Sylvie. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; Franci

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Produits dangereux : recherche et essais normalisés

International audienceLors de la fabrication, du stockage, du transport et de l'emploi de produits chimiques, il peut se produire accidentellement des incendies, des explosions et des dispersions et disseminations de polluants dans l'environnement au sein des eaux, des sols, de l'atmosphere. Les pollutions en cas d'accident ou d'incident de fabrication sont susceptibles d'engendrer de graves nuisances pour l'homme et pour les populations constituant les ecosystemes. II s'avere aujourd'hui indispensable de prevoir et d'evaluer les dangers presentes par ces produits

Synergie de l'immunothérapie et de la chimiothérapie pour l'induction de la présentation antigénique croisée par la microglie et le rejet tumoral dans un modèle pré-clinique de gliome murin

La présentation antigénique croisée permet de générer directement des lymphocytes T cytotoxiques, cellules les plus efficaces pour éliminer les cellules tumorales. Ce travail montre que les cellules microgliales adultes, principales cellules présentatrices d antigènes (CPA) du système nerveux central (SNC), et donc en première ligne face aux tumeurs cérébrales, sont capables in vivo de présenter de façon croisée des antigènes tumoraux issus de cellules tumorales mourantes traitées par un agent chimiothérapeutique (BCNU). Ainsi, la microglie constitue un appui pour l efficacité des réponses immunitaires anti-tumorales dans le cerveau. Cependant, pour une activation lymphocytaire optimale, cette aptitude est soumise à l injection d adjuvants destinés à contrer l immunosuppression locale du SNC. En parallèle, dans un modèle pré-clinique de gliome murin, le bénéfice de l association d une chimiothérapie administrée localement (BCNU) avec un protocole d immunothérapie a été étudié. La chimiothérapie permet l apoptose massive des cellules tumorales et donc la libération d antigènes. Le bras immunothérapeutique a pour but de lever une part de l immunosuppression tumorale par la déplétion des lymphocytes T régulateurs et à restimuler la réponse immunitaire via un agoniste du TLR9 capable de promouvoir l activation des CPA. L association de ces deux approches thérapeutiques permet ainsi à 93% des souris traitées de survivre ainsi que l induction d une réponse mémoire protégeant 43% d entre-elles d une seconde injection du gliome.Antigen cross-presentation induces cytotoxic T lymphocyte generation, the most efficient cells allowing tumor cell elimination. This work shows that adult microglial cells, the main antigen presenting cells (APC) of the central nervous system (CNS), in first line to brain tumors, are able to cross-present antigens from dying tumor cells treated by chemotherapy (BCNU) in vivo. Thus, microglia are necessary for anti-tumor immune response efficiency in the brain. Nevertheless, this ability is subjected to the injection of several adjuvants to counterbalance the local immunosuppression of the CNS and to obtain an optimal lymphocyte activation. Moreover, in a pre-clinical murine glioma model, we studied the benefit of the association of a local chemotherapy (BCNU) with an immunotherapeutic protocol. Chemotherapy enables a massive tumor apoptosis and therefore antigen release. The immunotherapeutic arm aims to remove a part of the tumor immunosuppression by the regulatory T lymphocyte depletion and to restimulate the immune response through a TLR9 agonist promoting APC activation. The combination of these two therapeutic approaches allows 93% of treated mice to survive and induces a memory immune response protecting 43% of them from tumor rechallenging.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

From Charpy to present impact testing

International audienc

Mechanical behaviour of materials. Vol 1 : Micro and macroscopic consitutive behaviour

International audienceForeword .- Chapter 1 Introduction.- Chapter 2 Elastic behaviour.- Chapter 3 Elastoplasticity.- Chapter 4 Elastoviscoplasticity.- Chapter 5 Viscoelasticity.- Annex I Atomic and molecular structures.- Annex II Phase transformations.- Annex III Continuum mechanics: basic concepts and equations.- Tables 1.- Tables 2.- Notations.- Author Index.- Subject Index

Mechanical behaviour of materials. Vol 2 : Fracture mechanics and damage

International audienceDesigning new structural materials, extending lifetimes and guarding against fracture in service are among the preoccupations of engineers, and to deal with these they need to have command of the mechanics of material behaviour. The first volume of this two-volume work deals with elastic and elastoplastic behaviour; this second volume continues with viscoelasticity, damage, fracture (resistance to cracking) and contact mechanics. As in Volume I, the treatment starts from the active mechanisms on the microscopic scale and develops the laws of macroscopic behaviour. Chapter I deals with viscoplastic behaviour, as shown, for example, at low temperatures by the effects of oscillatory loads and at high temperatures by creep under steady load. Chapter 2 treats damage phenomena encountered in all materials - for example, metals, polymers, glasses, concretes - such as cavitation, fatigue and stress-corrosion cracking. Chapter 3 treats those concepts of fracture mechanics that are needed for the understanding of resistance to cracking and Chapter 4 completes the volume with a survey of the main concepts of contact mechanics. As with Volume I, each chapter has a set of exercises, either with solutions or with indications of how to attack the problem; and there are many explanatory diagrams and other illustrations

Mechanical behaviour of materials. Vol 1 : Micro and macroscopic consitutive behaviour

International audienceForeword .- Chapter 1 Introduction.- Chapter 2 Elastic behaviour.- Chapter 3 Elastoplasticity.- Chapter 4 Elastoviscoplasticity.- Chapter 5 Viscoelasticity.- Annex I Atomic and molecular structures.- Annex II Phase transformations.- Annex III Continuum mechanics: basic concepts and equations.- Tables 1.- Tables 2.- Notations.- Author Index.- Subject Index