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International audience; Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

The design and control of walking robots is a great issue for researchers (high number of DOFs, coupled phenomena). They could benefit to the biomechanics community as testing beds for bio-inspired...

International audience; Histidine kinases (HKs) are primary sensor proteins that act in cell signaling pathways generically referred to as “two-component systems” (TCSs). TCSs are among the most widely distributed transduction systems used by both prokaryotic and eukaryotic organisms to detect and respond to a broad range of environmental cues. The structure and distribution of HK proteins are now well documented in prokaryotes, but information is still fragmentary for eukaryotes. Here, we have taken advantage of recent genomic resources to explore the structural diversity and the phylogenetic distribution of HKs in the prominent eukaryotic supergroups. Searches of the genomes of 67 eukaryotic species spread evenly throughout the phylogenetic tree of life identified 748 predicted HK proteins. Independent phylogenetic analyses of predicted HK proteins were carried out for each of the major eukaryotic supergroups. This allowed most of the compiled sequences to be categorized into previously described HK groups. Beyond the phylogenetic analysis of eukaryotic HKs, this study revealed some interesting findings: 1) characterization of some previously undescribed eukaryotic HK groups with predicted functions putatively related to physiological traits; 2) discovery of HK groups that were previously believed to be restricted to a single kingdom in additional supergroups, and 3) indications that some evolutionary paths have led to the appearance, transfer, duplication, and loss of HK genes in some phylogenetic lineages. This study provides an unprecedented overview of the structure and distribution of HKs in the Eukaryota and represents a first step toward deciphering the evolution of TCS signaling in living organisms.

In Press, Corrected Proof; International audience; Aims. – MicroRNAs (miRNAs) from extracellular vesicles (EVs) have been proposed as promising biomarkers for a number of diseases. In this study, their potential as urine-based biomarkers of diabetic nephropathy (DN) was assessed. Methods. – MiRNAs were profiled in urinary EVs from 160 fasting subjects with normal glucose tolerance (NGT) and in T2DM patients with either microalbumininuria (MIC) or macroalbuminuria (MAC). Results. – A total of 73 miRNAs detected in urinary EVs (NGT) were predicted to target important functions for kidney homoeostasis, thereby validating their use as indicators of kidney dysfunction. Indeed, a urinary EV miRNA signature was found to comprise increased levels of let-7i-3p, miR-24-3p and miR-27b-3p, and decreased levels of miR-15b-5p, to identify patients with MIC. ROC curve analysis confirmed this ability to identify MIC in normo-albuminuria T2DM (T2DM-NA) patients and to differentiate between MAC and T2DM patients. These miRNAs were also predicted to target protein networks involved in the Wnt/b-catenin signalling cascade, activin receptor signalling and cell differentiation/proliferation, and correlated with eGRF, HbA1c, serum creatinine, urea, albumin and blood pressure. Concentrations of miR-30a-5p were specifically modified in urinary EVs from patients with MAC, but not MIC, suggesting that miR-30a-5p could be related to severe kidney damage. Conclusion. – Urinary EV miRNAs correlate with the degree of MIC. As they are also thought to regulate pathways that are targets of pharmacological agents to prevent DN (reticulum stress, activin receptors), they may also serve as non-invasive ‘liquid biopsies’ to stratify patients at risk of developing MAC and to monitor treatment efficacy.

Two-component systems (TCSs) are widely distributed cell signaling pathways used by both prokaryotic and eukaryotic organisms to cope with a wide range of environmental cues. In fungi, TCS signaling routes, that mediate perception of stimuli, correspond to a multi-step phosphorelay between three protein families including hybrid histidine kinases (HHK), histidine phosphotransfer proteins (HPt) and response regulators (RR). The best known of these fungal transduction pathways remains the Sln1(HHK)-Ypd1(HPt)-Ssk1(RR) system that governs the high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway for osmo-adaptation in Saccharomyces cerevisiae. Although recent advances have provided a preliminary overview of the distribution of TCS proteins in the kingdom Fungi, underlying mechanisms that drive the remarkable diversity among HHKs and other TCS proteins in different fungal lineages remain unclear. More precisely, evolutionary paths that led to the appearance, transfer, duplication, and loss of the corresponding TCS genes in fungi have never been hitherto addressed. In the present study, we were particularly interested in studying the distribution of TCS modules across the so-called "budding yeasts clade" (Saccharomycotina) by interrogating the genome of 82 species. With the exception of the emergence of an additional RR (named Srr1) in the fungal CTG clade, TCS proteins Ypd1 (HPt), Ssk1 (RR), Skn7 (RR), and Rim15 (RR) are well conserved within the Saccharomycotina. Surprisingly, some species from the basal lineages, especially Lipomyces starkeyi, harbor several filamentous-type HHKs that appear as relict genes that have been likely retained from a common ancestor of Saccharomycotina. Overall, this analysis revealed a progressive diminution of the initial pool of HHK-encoding genes during Saccharomycotina yeast evolution.

International audience; Objectives: Species from the Scedosporium apiospermum complex rank the second among the filamentous fungi colonizing the respiratory tract of cystic fibrosis (CF) patients. Nevertheless, the pathogenesis of Scedosporium infections remains poorly understood. Notably, the mechanisms developed by these molds to establish within the bronchial tree are still unknown. Among the species from the S. apiospermum complex, four have been identified as capable to chronically colonize the CF respiratory tract (S. boydii, S. apiospermum, S. aurantiacum ,and S. minutisporum) whereas S. dehoogii , which is common in the environment is unable to establish chronically in the lungs of CF patients. Since several years, we aimed at identifying the key molecular mechanisms underlying the ability of Scedosporium species to establish within the respiratory tract of CF patients and to cause chronic colonization of the airways. Methods: To identify candidate genes potentially involved in the adaptation and pathogenicity of Scedosporium species, we recently performed two complementary omics approaches including transcriptomics and comparative genomics. First, the transcriptome of the S. apiospermum reference strain (IHEM14462) was compared in different growth conditions mimicking the various physio-chemical constraints encountered in the respiratory tract of CF patients (hypercapnia, hypoxia, acid pH, low osmolarity, increased lactate concentration). For the comparative genomic strategy, we sequenced 5 isolates from each of the five species S. boydii, S. apiospermum, S. aurantiacum, S. minutisporum, and S. dehoogii . To identify candidate proteins that may enable Scedosporium species to establish within the respiratory tract of CF patients, we first searched clusters of orthologous proteins with no copy found in S. dehoogi isolates but conserved in all other isolates. In a second time we also detected genes present in all pathogenic species, as well as in S. dehoogii but exhibiting in this last species point mutations potentially leading to a loss of function. Results: As revealed by the transcriptomic approach, while hypercapnia, increased lactate or low osmolarity modified the expression of a limited number of genes, the transcriptome of S. apiospermum was greatly influenced by hypoxia, growth at acid pH or in a cystic fibrosis synthetic medium. In addition, the whole-genome sequencing project of several isolates from the five Scedosporium species allowed to obtain a total of 2.4-8.9 mega-reads per isolate which permitted good quality draft genome assemblies. Finally, comparative genomics allowed to identify a series of 134 genes lost or with a loss of function in S. dehoogii but still functional in all other species. Conclusion: The transcriptomic changes observed during S. apiospermum exposure to the physico-chemical conditions en-countered in the respiratory tract of cystic fibrosis patients as well as the set of candidate genes revealed by the comparative genomic strategy would help deciphering in a near future the crucial mechanisms allowing these opportunistic pathogens to specifically adapt to the CF bronchial mucus.

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets.

Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

A novel gadolinium and cobalt based aluminide, namely Gd3Co4+xAl12−x (x = 0.50(3)) is shown to crystallize in the hexagonal Gd3Ru4Al12 structure-type (space-group P63/mmc, a = 8.6830(1) A, c = 9.3164(2) A at room temperature). The investigation of its magnetic properties revealed a reversible ferromagnetic ordering at TC ≈ 40 K but expanding in a wide temperature range, potentially due to the geometrical magnetic frustrations expected in this structure-type. The magnetocaloric properties of this intermetallic, determined from both magnetization and specific heat data, are dominated by a maximum entropy variation of −3.28 J kg−1 K−1 at 39(1) K and an adiabatic temperature change of about 1.5 K extending from 20 to 40 K, highlighting some interest for low temperature applications.

Big walking robots are complex multi-joints mechanical systems which crystallize the human will to confer their capabilities on artefacts, one of them being the bipedal locomotion and more especially the balance keeping against external disturbances. This thesis proposes a balance stabilizer under operating conditions displayed on the locomotor system BIP 2000.This anthropomorphic robot has got fifteen electrically actuated degree of freedom and an Industrial controller. A new software has been developed with an object-oriented programming approach in order to propose the modularity required by the emulated and natural human symmetry. This consideration leads to the development of a mathematical tool allowing the computation of every modelling of a serial robot which is the sum of multiple sub robots with already known modelling. The implemented software also enables the robot to run offline generated dynamic walking trajectories and to test the balance stabilizer.We explore in this thesis the feasibility of controlling the center of gravity of a multibody robotic system with electrostatic fields acting on its virtual counterpart in order to guarantee its balance. Experimental results confirm the potential of the proposed approach.; Les grands robots marcheurs sont des systèmes mécatroniques poly-articulés complexes qui cristallisent la volonté des humains de conférer leurs capacités à des artefacts, l’une d’entre elle étant la locomotion bipède, et plus particulièrement la conservation de l’équilibre face à des perturbations extérieures. Cette thèse propose un stabilisateur postural ainsi que sa mise en œuvre sur le système locomoteur BIP 2000.Ce robot anthropomorphique possède quinze degrés de libertés actionnés par moteurs électriques et a reçu un nouvel automate ainsi que des variateurs industriels lors de la mise à jour réalisée dans le cadre de ces travaux. Un contrôleur a été conçu et implémenté en suivant les principes de la programmation orientée objet afin de fournir une modularité qui s’inspire de la symétrie naturelle des humanoïdes. Cet aspect a conduit à l’élaboration d’un ensemble d’outils mathématiques permettant de calculer l’ensemble des modèles d’un robot composé de sous-robots dont on connaîtrait déjà les modèles. Le contrôleur permet notamment à la machine de suivre des trajectoires calculées hors ligne par des algorithmes de génération de marches dynamiques ainsi que de tester le stabilisateur postural.Ce dernier consiste en un contrôle en position du robot physique par la consigne d’un robot virtuel de modèle dégradé, commandé en effort, soumis à des champs électrostatiques contraignant sa configuration articulaire. Les tests effectués ont permis de montrer la faisabilité de la méthode.

The opportunistic fungal pathogen Scedosporium boydii is the most common Scedosporium species in French patients with cystic fibrosis. Here we present the first genome report for S. boydii, providing a resource which may enable the elucidation of the pathogenic mechanisms in this species.

International audience

Free radicals are often described as chemical compounds characterized by unpaired electrons in their outer orbital rendering them highly reactive species. In mammalians, studies on free radicals were focused on reactive oxygen species (ROS) or reactive nitrogen species (RNS) due to their relative importance in physiological as well as in pathological processes. These cellular compounds are produced by different physiological systems such as the aerobic metabolism and play a major role in cell signaling pathways but also in the host immune defenses against pathogenic microorganisms. ROS and RNS are highly reactive species with potentially harmful effects on any cellular components (lipids, proteins and nucleic acids) when produced with a high level. To maintain ROS and RNS at a non-toxic concentration, enzymatic and non-enzymatic cellular antioxidants coordinate the balance between their production and their degradation. Superoxide dismutases, catalases, glutathione system, thioredoxin system, peroxidase systems, flavohemoglobins and nitrate or nitrite reductases represent the prominent enzymatic antioxidants used to scavenge excess of internal as well as external ROS and RNS. Bacteria, fungi and parasites also display similar enzymatic activities to escape the host oxidative defenses during the immune response against infectious processes. Here we summarize current knowledge on the enzymatic systems that allow microorganisms to fight against ROS and RNS, and shed light on the role that take some of them in microbial infections. Such microbial protective systems are considered as virulence factors, and therefore represent key targets for diagnosis of the infections or development of anti-infectious drugs.

International audience; Histidine kinases (HKs) are among the most prominent sensing proteins studied in the kingdom Fungi. Their distribution and biological functions in early diverging fungi (EDF), however, remain elusive. We have taken advantage of recent genomic resources to elucidate whether relationships between the occurrence of specific HKs in some EDF and their respective habitat/lifestyle could be established. This led to the unexpected discovery of fungal HKs that share a high degree of similarity with receptors for plant hormones (ethylene and cytokinin). Importantly, these phytohormone receptor homologs are found not only in EDF that behave as plant root symbionts or endophytes but also in EDF species that colonize decaying plant material. We hypothesize that these particular sensing proteins promoted the interaction of EDF with plants, leading to the conquest of land by these ancestral fungi.

International audience; The numerical simulation of Friction Stir Welding (FSW) is carried out using an Arbitrary Lagrangian or Eulerian (ALE) formulation. Its computational cost is reduced by appealing to the parallel version recently developed within the Forge software. The accuracy of the numerical model is increased by enhancing the state variables remapping algorithm and by introducing a better suited time integration scheme based on the cylindrical coordinates. The pin and shoulder threads are modelled in order to account for this crucial phenomenon on material heating. The developed model provides quite satisfactory temperature fields for the FSW of a butt joint of 6061 aluminium, as compared to experimental results. It allows simulating welding defects such as tunnels holes or flashes. The study then focuses on numerical simulations and experimental measurements of a lap joint of a 7175 aluminium sheet on a 2024 aluminium sheet for an aeronautical application.

International audience

International audience; In order to support the design of such a complex process like Friction Stir Welding (FSW) for the aeronautic industry, numerical simulation software requires (1) developing an efficient and accurate Finite Element (F.E.) formulation that allows predicting welding defects, (2) properly modeling the thermo-mechanical complexity of the FSW process and (3) calibrating the F.E. model from accurate measurements from FSW experiments. This work uses a parallel ALE formulation developed in the Forge® F.E. code to model the different possible defects (flashes and worm holes), while pin and shoulder threads are modeled by a new friction law at the tool / material interface. FSW experiments require using a complex tool with scroll on shoulder, which is instrumented for providing sensitive thermal data close to the joint. Calibration of unknown material thermal coefficients, constitutive equations parameters and friction model from measured forces, torques and temperatures is carried out using two F.E. models, Eulerian and ALE, to reach a satisfactory agreement assessed by the proper sensitivity of the simulation to process parameters.

To delineate the direct effect of physical activity on adiponectin metabolism, we investigated the impact of contrasted physical activity changes, independent of body mass changes, on adiponectin plasma concentration and muscle sensitivity in lean and overweight adult males. Eleven physically active lean men (70.6 ± 2.1 kg) were subjected to 1-month detraining; 9 sedentary lean men (73.1 ± 3.3 kg); and 11 sedentary overweight men (97.5 ± 3.0 kg) participated in a 2-month aerobic-exercise training program. Diet was controlled to maintain stable energy balance. Body composition, VO2peak, circulating adiponectin, adipose and muscle tissue adiponectin, muscle adiponectin receptors, and APPL1 mRNAs were measured before and after the interventions. At baseline, plasma high-molecular-weight adiponectin concentration was lower in both active lean (5.44 ± 0.58 µg/mL) and sedentary overweight (5.30 ± 1.06 µg/mL) than in sedentary lean participants (7.44 ± 1.06 µg/mL; both p

International audience; This study investigated miR-148b as a potential physiological actor of physical inactivity-induced effects in skeletal muscle. By using animal and human protocols , we demonstrated that the early phase of transition toward inactivity was associated with an increase in muscle miR-148b content, which triggered the downregulation of NRAS and ROCK1 target genes. Using human myo-tubes, we demonstrated that overexpression of miR-148b decreased NRAS and ROCK1 protein levels, and PKB phosphorylation and glucose uptake in response to insulin. Increase in muscle miR-148b content might thus participate in the decrease in insulin sensitivity at the whole body level during the transition toward physical inactivity.

article i nfo Among marine organisms, little is known on patterns of intra-species habitat partitioning, whereas many studies have examined niche segregation at the multi-species community level. In this study, we investigated the fine-scale population structure and patterns of within-species habitat use of Indo-Pacific bottlenose dol- phins (Tursiops aduncus) in a tropical lagoon of the Indian Ocean (Mayotte, 45°10'E/12°50'S). First, we assessed genetic population structure using mtDNA and 14 microsatellite markers to determine if bottlenose dolphins around Mayotte belong to one or several panmictic groups. The analyses revealed no mitochondrial polymorphism and the presence of a single population at Hardy-Weinberg equilibrium. Second, we assessed whether a community structure exists within the bottlenose population. A community is an assemblage of individuals using a common home range. Photo-identification data were used to assess individual home range size and habitat preferences. Home range analysis revealed the presence of at least two communities of bottlenose dolphins around Mayotte: one occurring in the shallower waters inside the lagoon and a second in the vicinity of a deeper reef bank, situated further offshore in the northern part of the island. Stable isotope analyses of δ 13 C and δ 15 N were performed to detect intra-species segregation of habitat and resource use. However, no significant structure across the population was detected. Nevertheless, this study highlights that, even at small spatial scales, individual and between community variations of habitat preferences occur in bottlenose dolphin populations. Intra-species niche partitioning may explain habitat segregation in these insular delphinids.

In diving marine predators, such as pinnipeds, the development of diving and foraging skills prior to weaning might be critical to post-weaning survival. Here, we examined the effect of pup mass growth on the amount of time devoted to aquatic activities and the dive performance of Antarctic fur seal, Arctocephalus gazella, pups on Kerguelen Island. Maternal attendance and mass-specific growth rate were assessed for 85 pups. Two types of monitoring were applied: visual observations of behaviours for 60 pups and the deployment of time-depth recorders (TDRs) on 19 female pups. At approximately 2 months of age, pups demonstrated minimal diving behaviour, but displayed considerable aquatic activity. While mothers were foraging at sea, pups fasted on land (6.0 ± 1.3 d). As the mass-specific growth rate was different between sexes, only data on female pups were analysed (n = 31). Mass-specific growth rate was related to maternal attendance patterns and impacted the amount of time allocated by pups to aquatic activities. The time spent in the water by pups was quadratically related to fasting progress. This study shows the importance of growth and fasting progress on the quantity of time pups devoted to aquatic activities. Our results suggest that greater post-weaning survival of heavier pups may be due not only to their greater body reserves, as reported in several studies, but also possibly to from their greater aquatic skills and physiological adaptations developed during the suckling period.

Aspergillus fumigatus is the most prevalent thermophilic inhabitants of decaying vegetation and one of the most important human opportunistic fungal pathogens. Like other fungi, A. fumigatus cells are covered by a cell wall, which is both a protective, rigid exoskeleton and a dynamic structure, undergoing constant modification depending on its environment. The cell wall, in the majority of fungi, is composed of polysaccharides, and understanding the biochemical organization and biogenesis of an A. fumigatus cell wall is essential as this envelop is continuously in contact with the environment/host cell and acts as a sieve and reservoir for molecules, such as enzymes and toxins that play an active role during infection. This article is intended to give an overview of the biosynthesis of constituent cell wall polysaccharides and their postsynthetic modification in A. fumigatus, it also discusses the antifungal drugs that affect cell wall polysaccharide biosynthesis.

Since the invention of Friction Stir Welding (FSW) in 1991 by The Welding Institute (TWI), aeronautics industry has been investigating the possibility to use this process instead of riveting with the objective to lighten its structures and more particularly the aircrafts structure panels. Aircraft panels are often straightened with stringers and profiles which are joined to the outer skin. The qualification of FSW process in aeronautics requires producing very high quality joints with the longevity of tools, which requires fine tuning of process parameters such as the geometry of the welding tool (shoulder and pin dimensions, threads on pin and shoulder) and the advancing and rotating speeds. The aim of this work is to support the design of the process by numerical simulation. It has three parts: (1) developing an efficient and accurate Arbitrary Lagrangian or Eulerian (ALE) formulation within the parallel version of Forge® software, (2) modelling the FSW process and (3) calibrating the F.E. model and validating simulation results thanks to FSW experiments on lap joints.This work is based on the parallel ALE formulation developed in Forge® to model the different possible defects taking place in FSW (flashes and worm holes). The transport algorithm of continuous fields, required by the Eulerian frame, is enhanced to take the special characteristics of the FSW's flow into account (nodes located in input plan or flashes or in contact with the tool). A new time integration scheme based on cylindrical coordinates, which are best suited for this process, is introduced. Finally, the pin and shoulder threads are modelled by introducing a new friction law at the tool / material interface.This general and parallel ALE formulation is robust enough to model the FSW process. Thermomechanical results obtained are in agreement with previous results validated by experiences. And the numerical tool demonstrated its ability to model flashes formation and losses of contact behind the pin. Finally industrial welding lap joints configuration was studied. Experimental tests were conducted with several process parameters and type of lap joint. And measure of torque and forces in tool, and temperature in tool and sheet metal allowed to calibrate model parameters (friction, behavior law, thermal coefficients) and to validate FE results.; Depuis l'invention du soudage par frottement malaxage (FSW) en 1991 par The Welding Institute (TWI), l'industrie aéronautique envisage de remplacer l'assemblage par rivetage des tôles par ce procédé. L'objectif est d'alléger les structures, plus particulièrement les panneaux des structures d'aéronefs qui sont souvent raidis avec des lisses et des profilés assemblés à la peau extérieure. La qualification du procédé FSW dans l'aéronautique requiert de produire des joints de très haute qualité avec une longue durée de vie des outils. Ceci nécessite un réglage fin des paramètres procédé tels que la géométrie de l'outil (dimensions de l'épaulement et du pion, filetage) et les vitesses d'avance et de rotation. Le but de ce travail est d'accompagner la conception du procédé par la simulation numérique. Il comporte trois parties: (1) le développement de la formulation arbitrairement lagrangienne ou eulérienne (ALE) dans la version parallèle du logiciel Forge® pour l'adapter au FSW, (2) la modélisation du procédé FSW et (3) la calibration du modèle EF et la validation des résultats numériques suite à la réalisation d'essais FSW en configuration par recouvrement.Ce travail est basé sur la formulation ALE parallèle développée dans Forge® afin de modéliser les différents défauts caractéristiques du FSW (bavures et trous). L'algorithme de transport des champs continus, indispensable au caractère eulérien, est affiné afin de considérer les particularités de l'écoulement du procédé (nœud du plan d'entrée, en contact avec l'outil ou dans les bavures et sortant du domaine d'étude). Un nouveau schéma d'intégration temporelle basée sur les coordonnées cylindriques plus adapté à ce procédé fortement rotationnel est introduit. Enfin, un filetage sur l'outil est modélisé par l'introduction d'une nouvelle loi de frottement à l'interface outil / matière.Cette formulation ALE générale et parallèle a montré sa robustesse pour modéliser le procédé FSW. Les résultats thermomécaniques sont en accord avec de précédents résultats validés par l'expérience. De plus l'outil numérique obtenu a montré ses capacités pour la modélisation des bavures ou des pertes de contact derrière le pion.Finalement la configuration de soudage par recouvrement industrielle a été étudiée. Pour cela des essais expérimentaux ont été réalisés pour divers paramètres du procédé et divers types de joints de recouvrement. Puis les mesures de forces et du couple dans l'outil et de la température dans l'outil et la tôle ont permis de calibrer les paramètres du modèle (frottement, loi de comportement, coefficients thermiques) et de valider les résultats EF.

The Ce–Co–Al ternary phase diagram has been reinvestigated at 973 K by means of powder X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy and differential thermal analyses. It contains 5 ternary phases (CeCo 2 Al 8 , Ce 2 Co 6 Al 19 , CeCoAl 4 , Ce 3 Co 3 Al 4 and CeCoAl) as well as 7 extensions in the ternary field of pseudo-binaries (CeAl 2 − x Co x with 0 ⩽ x ⩽ 0.18; CeCo 2 − x Al x with 0 ⩽ x ⩽ 0.21; CeCo 3 − y Al y with 0 ⩽ y ⩽ 0.20; Ce 2 Co 7 − x Al x with 0 ⩽ x ⩽ 0.73; Ce 5 Co 19 − y Al y with 0 ⩽ y ⩽ 0.20; CeCo 5 − x Al x with 0 ⩽ x ⩽ 0.71 and Ce 2 Co 17 − y Al y with 0 ⩽ y ⩽ 2.2). Two liquid areas are present at the Al and Ce-rich corners of this isothermal section.

International audience; Friction stir welding on aluminum alloy is seen as an alternative solution to riveting 2024 and 7075 aluminum alloys pieces in order to lighten aircraft structure. On these alloys, mechanical properties are linked to structural hardening due to solid state precipitation. A coupling approach is proposed in order to manage the precipitates distribution evolution taking place during the process and predict final properties. At macro-scale, a model is used to get the thermal evolution in the different parts of the welded zone. At micro-scale, a time-efficient precipitation simulation is developed based on a reliable thermodynamic description. A particle size distribution approach (PSD) is proposed to predict the nucleation, growth, dissolution and coarsening of stable and metastable phases. An accurate yield strength model is applied on the final distribution. Calibration is performed on differential scanning calorimetry studies (DSC), hardening test and tensile tests for both isothermal, non-isothermal and weld samples.

International audience; Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians-an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

Scedosporium boydii is a pathogenic filamentous fungus that causes a wide range of human infections, notably respiratory infections in patients with cystic fibrosis. The development of new therapeutic strategies targeting S. boydii necessitates a better understanding of the physiology of this fungus and the identification of new molecular targets. In this work, we studied the conidium-to-germ tube transition using a variety of techniques including scanning and transmission electron microscopy, atomic force microscopy, two-phase partitioning, microelectrophoresis and cationized ferritin labeling, chemical force spectroscopy, lectin labeling, and nanoLC-MS/MS for cell wall GPI-anchored protein analysis. We demonstrated that the cell wall undergoes structural changes with germination accompanied with a lower hydrophobicity, electrostatic charge and binding capacity to cationized ferritin. Changes during germination also included a higher accessibility of some cell wall polysaccharides to lectins and less CH3/CH3 interactions (hydrophobic adhesion forces mainly due to glycoproteins). We also extracted and identified 20 GPI-anchored proteins from the cell wall of S. boydii, among which one was detected only in the conidial wall extract and 12 only in the mycelial wall extract. The identified sequences belonged to protein families involved in virulence in other fungi like Gelp/Gasp, Crhp, Bglp/Bgtp families and a superoxide dismutase. These results highlighted the cell wall remodeling during germination in S. boydii with the identification of a substantial number of cell wall GPI-anchored conidial or hyphal specific proteins, which provides a basis to investigate the role of these molecules in the host-pathogen interaction and fungal virulence.

Current lifestyle changes, notably sedentary behavior, are associated with chronic diseases, while regular activity improves metabolic functions The purpose of my work is to examine the effects of different level of physical activity, until extreme inactivity on cross-talk mediators, such as adiponectine and microRNAs, and on metabolism, notably in muscle or liver. We demonstrate a significant increase of hepatic markers under severe physical inactivity (60d bed-rest), showing the onset of a development of NASH. Our data support that regular exercise can limit these physical inactivity-induced metabolic alterations. We demonstrate that independently of effects of physical activity and inactivity on fat mass, adiponectin plasma concentrations were negatively related to physical activity level. Our data highlight that variations in total plasma adiponectin with physical activity level are mainly due to changes in HMW adiponectin plasma concentrations, and are unlikely explained by variations in expression of adiponectin in adipose tissue and muscle. We also show an inverse relation between fasting insulin plasma concentrations with both adiponectin receptors, and one of its downstream effector (APPL1) in the muscle, suggesting an improvement of adiponectin muscular sensitivity. During a contrasted and moderate physical activity intervention in human and mice, we show that transition from activity toward inactivity results in muscle miR-148b content increase, leading to muscle metabolism alteration. Our study on miR-148b expression modulation in vitro in human myotubes, show its involvement in insulin signaling pathway in muscle, suggesting that miR-148b accumulation in muscle could participate in the whole body insulin sensitivity degradation, which is a feature of persistent sedentary behavior. Altogether, these results demonstrate that the study of cross-talk actors is crucial to understand the mechanisms involved in active and inactive behaviors, and their effects on health, Les travaux de thèse présentés dans ce manuscrit ont pour but d’étudier les effets de différents niveaux d’activité physique, jusqu’à l’inactivité extrême sur des acteurs du dialogue inter-organe comme l’adiponectine et les microARNs, et sur le métabolisme, notamment dans le muscle ou le foie. Nous démontrons que l’inactivité physique extrême, dans le cadre d’un bedrest de 60 jours, augmente les marqueurs de l’inflammation hépatique, prémices du développement d’une stéato-hépatite non alcoolique. Nos données montrent que des exercices réguliers peuvent limiter les altérations métaboliques induites par l’inactivité physique. Nous montrons, ensuite qu’indépendamment des effets de l’activité et l’inactivité physique sur la masse grasse, les concentrations circulantes d’adiponectine sont inversement associées avec le niveau d’activité physique. Nous montrons notamment que les variations des taux circulants d’adiponectine totale avec le niveau d’activité physique sont principalement dû aux variations de la forme de haut poids moléculaire, et ne sont pas expliquées par des variations d’expression de l’adiponectine dans le tissu adipeux ou musculaire. Nous montrons également une relation inverse entre l’insulinémie plasmatique à jeun et les récepteurs de l’adiponectine, et un de ses effecteurs (APPL1) dans le muscle supportant l’amélioration de la sensibilité à l’adiponectine musculaire. Au cours d’une intervention contrastée et modérée sur le niveau d’activité physique chez l’homme et la souris, nous avons pu montrer que la transition d’un statut actif vers inactif augmentait le niveau d’expression de miR-148b dans le muscle, participant à la dégradation du métabolisme. Notre étude de modulation de l’expression de miR-148b in vitro dans les myotubes humains, montre son implication dans la voie de signalisation de l’insuline, et suggère que l’accumulation de miR-148b dans le tissu musculaire peut participer à l’altération de la sensibilité à l’insuline qui est caractéristique des comportements sédentaires persistants. L’ensemble de ces résultats démontrent que l’étude des acteurs de la signalisation inter-organe est cruciale pour comprendre les mécanismes mis en jeu par les comportements actifs et inactifs, et leurs effets sur la santé

Les histidine kinases (HK) sont des proteines « senseurs » impliquees dans des mecanismes de signalisation cellulaire utilises par les bacteries, les plantes et les champignons pour percevoir les signaux environnementaux et proposer une reponse adaptee. Si la fonction des HK chez les bacteries et les plantes est a present elucidee, les donnees dans ce domaine sont plus que fragmentaires pour les champignons. Quelques travaux recents suggerent cependant l’implication des HK dans la virulence d’especes pathogenes de l’homme ( Candida albicans , Cryptococcus neoformans et les champignons dimorphiques) [1] . Ainsi, aucune HK n’ayant ete identifiee a ce jour chez les animaux, ces proteines constituent de ce fait des cibles de choix pour le developpement de nouvelles molecules antimicrobiennes ( Fig. 1 ).

International audience; Le procédé de soudage par friction malaxage (FSW) permet le soudage à l’état solide d’alliages d’aluminium sans apport de matière et sans présenter de défauts de fissuration à chaud. Il est développé depuis une vingtaine d’années. Il apparait ainsi être, dans le domaine aéronautique, une alternative intéressante au rivetage, en conduisant à un allègement des structures. La garantie d’une tenue mécanique fiable, dans le cadre d’alliages à durcissement structural, nécessite de connaitre l’évolution des mécanismes de précipitation. La simulation représente une opportunité d’étudier ces évolutions, à travers l’étude des processus de germination, croissance, dissolution et coalescence des précipités. Le modèle proposé dans cette étude est un modèle de classe préconisé pour les traitements anisothermes et développé par Myhr et Grong. Il permet de simuler l’ensemble des phénomènes caractéristiques de la précipitation. Ce modèle est couplé au logiciel Thermocalc de calcul des équilibres thermodynamiques, et appliqué à l’étude de l’évolution de la précipitation de la phase S, lors du soudage FSW des alliages AA2024. Une calibration préalable de ce modèle est effectuée grâce aux résultats expérimentaux obtenus via une analyse DSC sur des échantillons prétraités. La simulation de ces essais conduit également à valider le modèle, en prédisant l’ensemble des évolutions des flux de chaleur attendues. Cette validation est étendue pour différents traitements anisothermes. Dans un second temps, le modèle est couplé à la simulation de l’évolution thermomécanique de pièces soudées, dans le cadre d’un suivi de particules. L’évolution des différents cellules du modèle, correspondant à des évolutions thermiques spécifiques (Fig1) permet de cartographier et prédire l’état de précipitation afin d’en déduire les propriétés mécaniques finales du joint soudé

This chapter mainly focuses on specific genes of Aspergillus fumigatus as well as genes missing in A. fumigatus but present in other Aspergillus species, with the aim to identify genes that encode particular functions specifically associated with the life-style of A. fumigatus. Species-specific comparisons shown in the chapter were based on the BLASTP program, with the pam250 substitution matrix to favor recognition of large similar segment pairs and the seg filter to mask compositionally biased regions in the query sequences. In each considered species, each nonunique protein is assigned to a class of paralogs. Clustering of genes responsible for secondary metabolite synthesis have been already identified in A. fumigatus. The survey of the genome led to the identification of a cluster of genes that seems specific to A. fumigatus. Among the 377 genes specific to A. fumigatus, 74% encode small proteins (shorter than 150 amino acids), whereas only 8% of the genes in the whole A. fumigatus genome encode such small proteins. Genome comparison studies in Aspergillus have shown that species- or genus-specific genes constitute a tiny part of the genome compared to other fungal species. Moreover, the analyses of A. fumigatus-specific genes have not been very informative in terms of gene functions and do not highlight any particular pathway which could be unique to this fungus. The chapter confirms that the eight analyzed Aspergillus species are closely related and shows that no major particular event of function loss or gain took place in A. fumigatus during its evolution.

National audience; Le procédé FSW est un procédé de soudage par frottement et malaxage dont la complexité résulte d'un très fort couplage thermomécanique. Nous présentons une nouvelle formulation Arbitrairement Lagrangienne ou Eulérienne (ALE) en vue de le modéliser avec précision. Son utilisation montre qu'elle est parfaitement adaptée à la simulation du FSW en 3D. Elle permet notamment de simuler des soudures de qualité ou la formation de défauts tels que les bavures ou les trous tunnels qui peuvent apparaître en arrière du pion. Des améliorations ont été apportées au logiciel afin d'augmenter la précision de la simulation. Un filetage numérique a ainsi été modélisé sur l'outil pour augmenter le malaxage du matériau. Le transport des champs continus a été perfectionné pour gérer des instabilités de surface.

International audience; BACKGROUND:SUN proteins are involved in yeast morphogenesis, but their function is unknown.RESULTS:SUN protein plays a role in the Aspergillus fumigatus morphogenesis. Biochemical properties of recombinant SUN proteins were elucidated.CONCLUSION:Both Candida albicans and Aspergillus fumigatus sun proteins show a β-(1,3)-glucanase activity.SIGNIFICANCE:The mode of action of SUN proteins on β-(1,3)-glucan is unique, new, and original. In yeasts, the family of SUN proteins has been involved in cell wall biogenesis. Here, we report the characterization of SUN proteins in a filamentous fungus, Aspergillus fumigatus. The function of the two A. fumigatus SUN genes was investigated by combining reverse genetics and biochemistry. During conidial swelling and mycelial growth, the expression of AfSUN1 was strongly induced, whereas the expression of AfSUN2 was not detectable. Deletion of AfSUN1 negatively affected hyphal growth and conidiation. A closer examination of the morphological defects revealed swollen hyphae, leaky tips, intrahyphal growth, and double cell wall, suggesting that, like in yeast, AfSun1p is associated with cell wall biogenesis. In contrast to AfSUN1, deletion of AfSUN2 either in the parental strain or in the AfSUN1 single mutant strain did not affect colony and hyphal morphology. Biochemical characterization of the recombinant AfSun1p and Candida albicans Sun41p showed that both proteins had a unique hydrolysis pattern: acting on β-(1,3)-oligomers from dimer up to insoluble β-(1,3)-glucan. Referring to the CAZy database, it is clear that fungal SUN proteins represent a new family of glucan hydrolases (GH132) and play an important morphogenetic role in fungal cell wall biogenesis and septation.

How as teacher we can help the pupils presenting school difficulties engendered by the separation of their parents? Numerous pupils had to support the divorce or the separation of their parents. In specifics cases, children cross this situation without too much difficulties but for the others it is more complicated: school difficulties and/or behavioral difficulties can appears. All these difficulties are in class. They can develop difficulties in class, as well from the point of view of learnings as of the behavior. The teacher can be in trouble in front of the situation : How a professor have to reacts? Does he have to act alone or does he have to develop a partnership? Does he have to help the pupil on the personal and/or school plan? What we can set up, in class, to bring it some help? To answer these questions, questionnaires and conversations were made with primary school teachers and with a "master G" (Member of the RASED). Thanks to it, the report propose runways of remediations and brings precision on teacher/RASED partnership but also onto the confidential character of the information which can be exchanged in this partnership.; Comment en tant qu'enseignant peut-on aider les élèves présentant des difficultés scolaires engendrées par la séparation de leurs parents ? De nombreux élèves ont dû faire face ou font face au divorce ou à la séparation de leurs parents. Dans certains cas, les enfants traversent cette situation sans trop d'encombres mais pour d'autres cela est plus difficile : ils peuvent développer des difficultés en classe, aussi bien sur le plan des apprentissages que du comportement. L'enseignant peut se retrouver en difficulté face à la situation : que doit-il faire face à ces difficultés ? Doit-il agir seul ou doit-il développer un partenariat ? Comment peut-il aider l'élève sur le plan personnel et/ou scolaire ? Que mettre en place, en classe, pour lui apporter une aide ? Pour répondre à ces questions, des questionnaires et des entretiens ont été effectués auprès de professeurs des écoles et d'une maitre G (Membre du RASED). Grâce à cela, le mémoire propose des pistes de remédiations et apporte des précisions sur le partenariat enseignant/RASED mais également sur le caractère confidentiel des informations qui peuvent être échangées dans le cadre de ce partenariat.

Inelastic scattering of 84 MeV/u 17 O projectiles has been used to excite the giant resonances (GR) in 232 Th. The deduced parameters (width, energy, EWSR) of the isoscalar giant quadrupole resonance are in agreement with the known systematics. The observed giant monopole resonance strength, 100% of the EWSR, is consistent with other recent experimental results using heavy-ion projectiles. Strength is also observed at high excitation energy. The fission probability of GR in 232 Th has been measured by detecting the fission fragments in coincidence with the inelastically scattered particles. A structure is observed in the fission coincidence spectrum around 10 MeV, which can be attributed to the fission decay of giant resonances. The measured fission probability is consistent with statistical decay of the GQR.

MgtC is important for the survival of several bacterial pathogens in macrophages and for growth under magnesium limitation. Among eukaryotes, a gene homologous to mgtC was found only in the pathogenic fungus Aspergillus fumigatus . Our data show that the A. fumigatus MgtC (AfuMgtC) protein does not have the same function as the bacterial MgtC proteins.

The β(1-3)glucanosyltransferase GEL family of Aspergillus fumigatus contains 7 genes, among which only 3 are expressed during mycelial growth. The role of the GEL4 gene was investigated in this study. Like the other Gelps, it encodes a glycosylphosphatidylinositol (GPI)-anchored protein. In contrast to the other β(1-3)glucanosyltransferases analyzed to date, it is essential for this fungal species.