Full field modeling of recrystallization and grain growth thanks to a level set approach: towards modeling by industry

International audienceMetal forming modeling can be predictive only if the strain rate, strain and temperature dependency of the flow behaviour are correctly described. The mechanical properties and behaviour of metallic materials mainly depends on the content and structure of dislocation network, this points out the need to incorporate microstructure concepts into the numerical models. The goal is to correctly describe the main physical mechanisms occurring in metals during thermomechanical processes i.e. work-hardening, recovery, grain boundary migration, nucleation and grain growth related to dynamic, static or metadynamic recrystallization. Macroscopic and homogenized models are widely used in the industry, mainly due to their low computational cost. If this mean field framework is quite convenient, it can be synonymous, for a given material, with a large amount of experiments with advanced laboratory devices. Moreover, the homogenization of the microstructure does not permit to capture some very local phenomena

Rôle de la signalisation purinergique au cours de la régénération du foie chez la souris (étude des récepteurs P2X4 et P2X7)

Objectif : La régénération hépatique est un processus complexe qui met en jeu de nombreux signaux régulateurs endocrines, paracrines, autocrines et nerveux. L ATP extracellulaire et plus généralement la signalisation purinergique, ont été décrits comme ayant un rôle dans la survie et la prolifération cellulaires ainsi que dans les processus inflammatoires et sécrétoires. Le laboratoire a rapporté antérieurement que l ATP extracellulaire contribuait à la régénération du foie chez le rat. L objectif de ce travail était d étudier le rôle des récepteurs ionotropiques P2X4 et P2X7 au cours de la régénération hépatique après hépatectomie des deux tiers (Hx) chez la souris. Résultats : Les récepteurs P2X4 et P2X7 étaient fortement exprimés par les cellules de Kupffer et par les hépatocytes avec, pour le récepteur P2X4, un renforcement canaliculaire et sous-canaliculaire. Après Hx, un retard de régénération par rapport aux souris WT (restauration de la masse du foie, expression protéique de la cycline D1 et du PCNA, entrée en mitose des hépatocytes), ainsi que des lésions de nécrose hépatique et une cholestase prolongée étaient observés chez les souris P2X4 KO mais pas chez les P2X7 KO. La réponse adaptative hépatocytaire à la surcharge en acides biliaires après Hx n était pas altérée chez les souris P2X4 KO (vs WT) (régulation transcritpionnelle de CYP7a1, NTCP, et OSTb), alors que l adaptation du flux biliaire et de la sécrétion d HCO3- dans la bile était anormale. Enfin, une réponse inflammatoire exacerbée était observée après Hx chez les souris P2X4 KO, (ARNm et concentrations plasmatiques de IL-1b, TNF-a et IL-6) par rapport aux souris WT. In vitro, le récepteur P2X4 n avait pas d impact significatif sur la prolifération hépatocytaire, ni sur la réponse au LPS (lipopolysaccharide) ou à l ATP des macrophages péritonéaux (MP). Conclusion : Pendant la régénération du foie, le récepteur P2X4 contribuerait au contrôle de l homéostasie bilaire et de la réponse inflammatoire, deux éléments dont la régulation est essentielle au bon déroulement du processus de régénération. Les mécanismes par lesquels le récepteur P2X4 régule ces différents processus restent à déterminer.Background : Liver regeneration is a complex process during which various endocrine, paracrine, autocrine and nervous factors play important roles. Extracellular ATP and more generally purinergic signalling has been described to regulate cell survival and proliferation, as well as inflammatory processes. We previously reported that extracellular ATP contributed to liver regeneration in the rat. In this work, we analysed the involvement of the membrane ionotropic P2X4 and P2X7 purinergic receptors during liver regeneration after a two-third partial hepatectomy (PH) in mice. Results : P2X4 and P2X7 receptors were highly expressed in Kupffer cells, and in hepatocytes with reinforcement in the sub-canalicular and canalicular areas for P2X4 receptor. After PH, there was a delay in P2X4 KO as compared to WT mice, in liver mass restoration, cyclin D1 and PCNA expression, and mitotic activity. Post-PH hepatocyte necrosis (periportal focal bile infarcts ) and prolonged cholestasis were observed in P2X4-KO mice, but neither WT, nor P2X7 KO mice. Adaptive response to post-PH cholestasis (CYP7a1, NTCP and OSTb mRNA regulation) was similar in WT and P2X4-KO livers. In P2X4 KO mice after PH, as compared with WT, smaller increase in bile flow and HCO3- biliary output were observed. Early mRNA induction, as well as plasma concentration rise in cytokines (IL1 b, TNFa and IL6) were greater in P2X4-KO than WT mice after PH. In vitro, the P2X4 receptor didn t impact significantly hepatocyte proliferation, nor peritoneal macrophages (PM) inflammatory reponse to LPS (lipopolysaccharide) or ATP. Conclusions : During liver regeneration, P2X4 may contribute to the complex control of hepatocyte proliferation through the regulation of biliary homeostasis and inflammation. Mechanisms underlying P2X4 involvement in those processes still remain to be definedPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Water infiltration in an aquifer recharge basin affected by temperature and air entrapment

Artificial basins are used to recharge groundwater and protect water pumping fields. In these basins, infiltration rates are monitored to detect any decrease in water infiltration in relation with clogging. However, miss-estimations of infiltration rate may result from neglecting the effects of water temperature change and air-entrapment. This study aims to investigate the effect of temperature and air entrapment on water infiltration at the basin scale by conducting successive infiltration cycles in an experimental basin of 11869 m(2) in a pumping field at Crepieux-Charmy (Lyon, France). A first experiment, conducted in summer 2011, showed a strong increase in infiltration rate; which was linked to a potential increase in ground water temperature or a potential dissolution of air entrapped at the beginning of the infiltration. A second experiment was conducted in summer, to inject cold water instead of warm water, and also revealed an increase in infiltration rate. This increase was linked to air dissolution in the soil. A final experiment was conducted in spring with no temperature contrast and no entrapped air (soil initially water-saturated), revealing a constant infiltration rate. Modeling and analysis of experiments revealed that air entrapment and cold water temperature in the soil could substantially reduce infiltration rate over the first infiltration cycles, with respective effects of similar magnitude. Clearly, both water temperature change and air entrapment must be considered for an accurate assessment of the infiltration rate in basins

Defective angiogenesis in CXCL12 mutant mice impairs skeletal muscle regeneration

International audienceDuring muscle regeneration, the chemokine CXCL12 (SDF-1) and the synthesis of some specific heparan sulfates (HS) have been shown to be critical. CXCL12 activity has been shown to be heavily influenced by its binding to extracellular glycosaminoglycans (GAG) by modulating its presentation to its receptors and by generating haptotactic gradients. Although CXCL12 has been implicated in several phases of tissue repair, the influence of GAG binding under HS influencing conditions such as acute tissue destruction remains understudied

Limitation of gene flow by distance in the common yellow jasmine (Chrysojasminum fruticans, Oleaceae): implications for the study of its mating strategies

International audienceThe common yellow jasmine (Chrysojasminum fruticans; Oleaceae) is a distylous shrub occurring in the wild in southwestern Europe and the Mediterranean Basin. Little is known about the genetics of its populations and such information would be necessary to investigate its spread and mating strategies. Here, the organization of its genetic diversity was investigated among and between 13 populations from southern France, including a 35-years old experimental plot ('CEFE', CNRS Montpellier). Markers (microsatellites and indels) were developed to screen polymorphisms in nuclear, chloroplast, and mitochondrial genomes. Low linkage disequilibrium was observed between chloroplast and mitochondrial haplotypes likely resulting from paternal leaks in their inheritance as reported in other species of tribe Jasmineae. Yet, analyses of 36 progenies issued from parents with distinct chloroplast and/or mitochondrial DNA haplotypes only revealed a maternal contribution. Natural populations of C. fruticans are moderately to highly differentiated at the regional scale with a strong isolation-by-distance pattern detected on nuclear data, indicating limited gene flow. An isolated site ('Moulis'), located on the marginal distribution area, was remarkably genetically depauperate and highly differentiated from other populations. Further studies on the variation of mating strategies in C. fruticans should consider populations with contrasting patterns of genetic diversity. The artificial 'CEFE' population also offers opportunities for experiments in a closed system

The Receptor TGR5 Protects the Liver From Bile Acid Overload During Liver Regeneration in Mice

Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH) to initiate growth, protect liver cells, and sustain functions of the remnant liver. Bile acids (BAs), whose levels rise in the blood early after PH, stimulate both hepatocyte proliferation and protection, in part through their binding to the nuclear farnesoid X receptor (FXR). However, the effect of the BA receptor, TGR5 (G-protein-coupled BA receptor 1) after PH remains to be studied. Liver histology, hepatocyte proliferation, BA concentrations (plasma, bile, liver, urine, and feces), bile flow and composition, and cytokine production were studied in wild-type (WT) and TGR5 KO (knockout) mice before and after PH. BA composition (plasma, bile, liver, urine, and feces) was more hydrophobic in TGR5 KO than in WT mice. After PH, severe hepatocyte necrosis, prolonged cholestasis, exacerbated inflammatory response, and delayed regeneration were observed in TGR5 KO mice. Although hepatocyte adaptive response to post-PH BA overload was similar in WT and TGR5 KO mice, kidney and biliary adaptive responses were strongly impaired in TGR5 KO mice. Cholestyramine treatment, as well as Kupffer cell depletion, significantly improved the post-PH TGR5 KO mice phenotype. After bile duct ligation or upon a cholic acid-enriched diet, TGR5 KO mice exhibited more severe liver injury than WT as well as impaired BA elimination in urine. Conclusion: TGR5 is crucial for liver protection against BA overload after PH, primarily through the control of bile hydrophobicity and cytokine secretion. In the absence of TGR5, intrahepatic stasis of abnormally hydrophobic bile and excessive inflammation, in association with impaired bile flow adaptation and deficient urinary BA efflux, lead to BA overload-induced liver injury and delayed regeneration. (Hepatology 2013;58:1451-1460

Comparative Study of Injury Models for Studying Muscle Regeneration in Mice.

International audienceA longstanding goal in regenerative medicine is to reconstitute functional tissues or organs after injury or disease. Attention has focused on the identification and relative contribution of tissue specific stem cells to the regeneration process. Relatively little is known about how the physiological process is regulated by other tissue constituents. Numerous injury models are used to investigate tissue regeneration, however, these models are often poorly understood. Specifically, for skeletal muscle regeneration several models are reported in the literature, yet the relative impact on muscle physiology and the distinct cells types have not been extensively characterised. We have used transgenic Tg:Pax7nGFP and Flk1GFP/+ mouse models to respectively count the number of muscle stem (satellite) cells (SC) and number/shape of vessels by confocal microscopy. We performed histological and immunostainings to assess the differences in the key regeneration steps. Infiltration of immune cells, chemokines and cytokines production was assessed in vivo by Luminex®.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models

Modélisation en champ complet des phénomènes de recristallisation et de croissance de grains par une approche level-set : un outil de simulation avancée adapté à un usage industriel

Modélisation de la cristallisationSF2M infoLa simulation thermomécanique de la mise en forme des matériaux métalliques est prédictive, d'un point de vue macroscopique, si la dépendance de la contrainte d'écoulement vis-à-vis de la déformation, de la vitesse de déformation, et de la température est décrite par une loi de comportement adaptée. Les propriétés mécaniques et le comportement rhéologique des matériaux métalliques dépendent fortement de la densité de dislocations et des structures constituées au sein du réseau de dislocations. Il apparaît donc naturel d'incorporer ces aspects métallurgiques dans les outils de simulation numérique afin de décrire les principaux mécanismes physiques à l'oeuvre dans le matériau déformé : écrouissage, restauration, migration des joints de grains, germination et croissance de grains recristallisés, que ce soit en conditions statiques (au cours du chauffage ou traitement thermique), dynamiques (pendant une déformation à chaud) ou post-dynamiques. Cette étape est nécessaire au développement de modèles avec un fondement physique qui soient capables de prédire l'évolution du matériau lui-même, ou plus exactement de sa microstructure. Des modèles macroscopiques et homogénéisés sont assez fréquemment utilisés dans l'industrie, notamment parce qu'ils ne nécessitent pas de moyens de calculs particuliers, qu'ils sont assez simples et rapides à mettre en oeuvre [1, 2]. Ces avantages doivent néanmoins être nuancés par le fait que ces modèles nécessitent de réaliser au préalable un grand nombre de mesures expérimentales impliquant des moyens d'analyse parfois assez lourds, afin d'identifier les valeurs de paramètres adaptés à chaque cas (matériau/procédé). De plus, le principe même de l'homogénéisation peut empêcher de décrire les phénomènes métallurgiques locaux apparaissant de manière hétérogène dans la microstructure. Depuis une quinzaine d'années, des modèles à plus fine échelle, appelés modèles en champ complet, ont été développés pour décrire explicitement la microstructure et simuler son évolution [3-5] à l'échelle du polycristal. L'idée sous-jacente est que le réseau de joints de grains, sa morphologie et sa topologie jouent un rôle primordial dans l'évolution de la microstructure, il faut donc le prendre en compte de manière aussi fine que possible. Une nouvelle approche en champ complet, basée sur la description des interfaces au moyen de fonctions distance (level-set) dans un contexte éléments-finis (EF), a été introduite pour modéliser la recristallisation statique (incluant le phénomène de germination) en deux puis trois dimensions, et a ensuite été étendue à la modélisation de la croissance de grains [6-8]. L'un des avantages de cette méthode est que le phénomène d'ancrage de joints de grains par des particules de seconde phase (« Smith-Zener pinning »), qui apparaît dans de nombreux alliages industriels, est pris en compte de manière naturelle, sans introduire d'hypothèse simplificatrice ou de paramètre spécifique [9]. L'inconvénient majeur des modèles en champ complet est qu'ils sont souvent très couteux d'un point de vue numérique, ce qui peut même devenir rédhibitoire pour certains calculs en trois dimensions. Par ailleurs, ils reposent sur de nombreux paramètres dont l

The P2X4 purinergic receptor impacts liver regeneration after partial hepatectomy in mice through the regulation of biliary homeostasis

International audienceno abstrac

A hemizygous supergene controls homomorphic and heteromorphic self-incompatibility systems in Oleaceae

International audienceSelf -incompatibility (SI) has evolved independently multiple times and prevents self -fertilization in hermaphrodite angiosperms. Several groups of Oleaceae such as jasmines exhibit distylous flowers, with two compatibility groups each associated with a specific floral morph. 1 Other Oleaceae species in the olive tribe have two compatibility groups without associated morphological variation. 2-5 The genetic basis of both homomorphic and dimorphic SI systems in Oleaceae is unknown. By comparing genomic sequences of three olive subspecies ( Olea europaea ) belonging to the two compatibility groups, we first locate the genetic determinants of SI within a 700 -kb hemizygous region present only in one compatibility group. We then demonstrate that the homologous hemizygous region also controls distyly in jasmine. Phylogenetic analyses support a common origin of both systems, following a segmental genomic duplication in a common ancestor. Examination of the gene content of the hemizygous region in different jasmine and olive species suggests that the mechanisms determining compatibility groups and floral phenotypes (whether homomorphic or dimorphic) in Oleaceae rely on the presence/absence of two genes involved in gibberellin and brassinosteroid regulation