Lipids droplets are induced by hypoxia in avian skin cells in vitro and their targeting by Marek's Disease Virus is linked to virulence

The skin is composed of a dermis and an epidermis, mainly composed of fibroblasts and keratinocytes, respectively. In vivo, the epidermis is among the tissues showing the lower oxygen pressure (pO2), between 1 and 5%. Below 5% of O2, the tissue is usually considered as hypoxic, even when physiological. In mammals, hypoxia was shown to induce lipid droplets (LDs). Interestingly, avian keratinocytes naturally display numerous LDs, that rearrange during the keratinocyte differentiation process occurring between the basal and the transitional layer of the epidermis. To address if hypoxia could contribute to LDs reorganization, we cultured stem-cell-derived chicken keratinocytes in hypoxia (1% O2) for 65h and compared their LDs contents to cells in normoxia by microscopy. The number and size of LDs increased significantly under hypoxia in keratinocytes. LDs were also induced by hypoxia in primary fibroblasts normally devoid of LDs in normoxia. In addition, we demonstrate that the pUL51 protein from Marek's Disease Virus, an important pathogen of chickens that naturally infects keratinocytes, associates to LDs and that this association correlates with virulence in infected chickens. Altogether, our results demonstrate that hypoxia induces lipid droplets in chicken cells, and that their targeting by pUL51 is linked to MDV virulence in its natural host

Establishment of a culture model for the prolonged maintenance of chicken feather follicles structure in vitro

International audienceProtocols allowing the in vitro culture of human hair follicles in a serum free-medium up to 9 days were developed 30 years ago. By using similar protocols, we achieved the prolonged maintenance in vitro of juvenile feather follicles (FF) microdissected from young chickens. Histology showed a preservation of the FF up to 7 days as well as feather morphology compatible with growth and/or differentiation. The integrity of the FF wall epithelium was confirmed by transmission electron microscopy at Day 5 and 7 of culture. A slight elongation of the feathers was detected up to 5 days for 75% of the examined feathers. By immunochemistry, we demonstrated the maintenance of expression and localization of two structural proteins: scaffoldin and fibronectin. Gene expression (assessed by qRT-PCR) of NCAM, LCAM, Wnt6, Notch1, and BMP4 was not altered. In contrast, Shh and HBS1 expression collapsed, DKK3 increased, and KRT14 transiently increased upon cultivation. This indicates that cultivation modifies the mRNA expression of a few genes, possibly due to reduced growth or cell differentiation in the feather, notably in the barb ridges. In conclusion, we have developed the first method that allows the culture and maintenance of chicken FF in vitro that preserves the structure and biology of the FF close to its in vivo state, despite transcriptional modifications of a few genes involved in feather development. This new culture model may serve to study feather interactions with pathogens or toxics and constitutes a way to reduce animal experimentation

Study of the static and dynamic behaviour of PU foam: from the material sample to the automotive seat.

International audienceThis study concerns the vibrational comfort of automotive seats. It is commonly characterized by the seattransmissibility, obtained by computing the ratio of the acceleration at the seat surface to the one at the seat base.This curve, observed in the frequency domain, depicts the seat performance in terms of vibrations filtration. Thetransmissibility is computed on a loaded structure, which means that an initial compression is present. Sincethe complete seat is a complex system, the first part of the paper presents static and dynamic experiments andsimulations on a foam sample. The experiments are then reproduced using a finite element model. In thecase of the static compression tests, the stress-strain curve is chosen as validation criterion. The simulationshows that for strains lower than 75%, the model is accurate. In the case of the dynamic experiment, themeasured and simulated transmissibilities are compared. While the resonance and cut-off frequencies are closeto the experimental results, the gain at the resonance is overestimated. The second section presents static anddynamic measurements performed on a seat cushion loaded by a rigid mass. The results show that the trim hasan impact on the measured displacements and pressure distributions. In dynamics, it also has an impact on theresonance peak of the transmissibility. Finally, the simulation process proposed to validate the complete seatmodel is presente

La flexibilité cognitive : une dimension cognitive clé

International audienceCognitive flexibility, an essential executive function, allows adaptation to environmental changes and represents a fundamental pillar of executive function in neuropsychological models. Based on neurobiological advances and clinical observations, it has emerged as a promising transdiagnostic marker for several psychiatric pathologies, including mood disorders, schizophrenia, and autism spectrum disorders. This review examines the specific role of cognitive flexibility among other cognitive functions, explores potential therapeutic approaches, and presents its evaluation in human and animal models as part of PEPR PROPSY. As the chapters unfold, readers will deepen their understanding of cognitive flexibility while discovering promising avenues for both assessment methods and intervention strategies.La flexibilité cognitive est une fonction exécutive fondamentale qui permet de s’adapter aux changements environnementaux, et constitue un marqueur transdiagnostique prometteur dans plusieurs troubles psychiatriques. Cette revue examine le rôle spécifique de la flexibilité cognitive parmi les autres fonctions cognitives. Elle explore les approches thérapeutiques potentielles, et présente son évaluation dans le cadre du PEPR PROPSY. À travers ses différentes sections, le lecteur peut ainsi approfondir ses connaissances sur la flexibilité cognitive, et découvrir des pistes encourageantes, tant pour son évaluation que pour son ciblage dans l’optique d’approches interventionnelles

Hypoxia and HIF-1 Trigger Marek’s Disease Virus Reactivation in Lymphoma-Derived Latently Infected T Lymphocytes

Latent-to-lytic switch of herpesviruses (also known as reactivation) is responsible for pathology recurrences and/or viral shedding. Studying physiological triggers of reactivation is therefore important for health to limit lesions and viral transmission.</jats:p

Stimulation du nerf vague dans le traitement de la dépression

International audienceVagus nerve stimulation (VNS) is an old, yet new, option for treatment-resistant depression. Despite several clinical trials over the last 15 years showing a consistent benefit-risk balance of the technic, VNS still struggles to find its place in our therapeutic algorithms. This is especially true in France, where only a few surgeries have been performed nationwide, all in the last year. The reasons behind this lag are manifolds; (1) psychiatrists usually do not consider surgical treatments, even when they are minimally invasive and reversible, (2) early VNS trials stumbled on methodological difficulties that are common to all invasive neurostimulation technics, and initially failed to provide strong evidence for its efficacy, and (3) VNS requires multidisciplinary teams involving psychiatrists and neurosurgeons that did not exist then. Nevertheless, studies of the past twenty years support VNS as a treatment of depression endowed with a unique efficacy profile: a long runner best at maintaining remission in hard-to-stabilize depression, even in the context of ECT withdrawal, and irrespective of whether it is unipolar or bipolar. Thus, VNS potentially addresses the unmet medical needs of some of the most severe and chronic patients with depression. This review aims at introducing VNS as a treatment option for depression, summarizing available evidence for its efficacy and tolerance, and delineating patient profiles that might benefit the most of such treatment

Hypoxia and HIF-1 trigger Marek’s Disease Virus reactivation in lymphoma-derived latently infected T lymphocytes

International audienceLatency is a hallmark of herpesviruses, allowing them to persist into their host without virions production. Acute exposure to hypoxia (below 3% O 2 ) was identified as a trigger of latent-to-lytic switch (reactivation) for human oncogenic gamma-herpesviruses (KSHV and EBV). Therefore, we hypothesized that hypoxia could also induce reactivation of Marek’s disease virus (MDV), sharing biological properties with EBV and KSHV (notably oncogenic properties), into lymphocytes. Acute exposure to hypoxia (1% O 2 ) of two MDV-latently infected cell lines derived from MD tumors (3867K and MSB-1) induced MDV reactivation. A bioinformatic analysis of the RB-1B MDV genome revealed 214 putative hypoxia-response element consensus sequences on 119 open reading frames. RT-qPCR analysis showed five MDV genes strongly upregulated early after hypoxia. In 3867K cells under normoxia, pharmacological agents mimicking hypoxia (MLN4924 and CoCl 2 ) increased MDV reactivation, but to a lower level than real hypoxia. Overexpression of wild-type or stabilized human hypoxia inducible factor-1α (HIF-1α) in MSB-1 cells in normoxia also promoted MDV reactivation. In such conditions, lytic cycle was detected in cells with a sustainable HIF-1α expression, but also in HIF-1α negative cells, indicating that MDV reactivation is mediated by HIF-1, in a direct and/or indirect manner. Lastly, we demonstrated by a reporter assay that HIF-1α overexpression induced the transactivation of two viral promoters, shown upregulated in hypoxia. These results suggest that hypoxia may play a crucial role in the late lytic replication phase observed in vivo in MDV-infected chickens exhibiting tumors, since a hypoxic microenvironment is a hallmark of most solid tumors. IMPORTANCE Latent-to-lytic switch of herpesviruses (aka reactivation) is responsible for pathology recurrences and/or viral shedding. Studying physiological triggers of reactivation is therefore important for health to limit lesions and viral transmission. Marek's disease virus (MDV) is a potent oncogenic alpha-herpesvirus establishing latency in T-lymphocytes and causing lethal T-lymphomas in chickens. In vivo , a second lytic phase is observed during tumoral stage. Hypoxia being a hallmark of tumors, we wondered whether hypoxia induces MDV reactivation in latently-infected T-lymphocytes, like previously shown for EBV and KSHV in B-lymphocytes. In this study, we demonstrated that acute hypoxia (1% O2) triggers MDV reactivation in two MDV transformed T-cell lines. We provide some molecular basis of this reactivation by showing that hypoxia inducible factor (HIF-1) overexpression induces MDV reactivation to a similar extend than hypoxia after 24 hours. Hypoxia is therefore a reactivation stimulus shared by mammalian and avian oncogenic herpesviruses of different genus

High-Resolution Morphobathymetric Analysis and Evolution of Capbreton Submarine Canyon Head (Southeast Bay of Biscay—French Atlantic Coast) over the Last Decade Using Descriptive and Numerical Modeling

In this study, the Capbreton canyon head, just off the coast, is investigated using high-resolution multibeam bathymetry datasets, sediment samples and numerical modeling. The HR bathymetry analysis reveals a morphological connection between the longshore trough and the head of the canyon. The analysis of recent sediment samples shows a clear correlation between the sediment of the canyon head and that of the nearshore. Hydrodynamic modeling (a coupled wave-flow model) shows that for high-energy waves, the rotational nature of surf-zone circulation reverses and wave-induced currents have the potential to transport large quantities of nearshore sands toward the canyon head. All these arguments support the assumption that the canyon head captures a part of the sand transported by longshore drift. Over the 15 years of observation (1998–2013), time-lapse bathymetry shows that the floor of the canyon head and one lateral gully network experienced significant morphological reworking. In terms of hazards, despite this strong activity, the position of the canyon head and the profile of its longitudinal slope remained stable and appears as a comforting factor. However, the activity of unusual lateral erosions needs to be monitored

Simulation du confort vibratoire d’un siège d’automobile par éléments finis

International audienceCette étude s’intéresse au confort vibratoire des sièges d’automobile. Celui-ci est communément caractérisé par la transmissibilité du siège, qui est obtenue en faisant le rapport de l’accélération à la surface du siège et de l’accélération à sa base. Cette courbe, observée dans le domaine fréquentiel, permet de connaître la performance de filtration des vibrations du siège. L’objectif de cette étude est de simuler de manière prédictive cette transmissibilité par éléments finis. Dans un premier temps, le modèle de siège fourni est présenté. Celui a été initialement développé pour des calculs en dynamique rapide, et contient donc des choix de modélisation des liaisons qui ont été changés pour adapter le modèle à des calculs en basses fréquences (de 0 à 20Hz). La comparaison des fréquences et déformées propres montre que cette modification n’altère pas le comportement modal du siège. Celui-ci peut alors être utilisé pour un calcul de transmissibilité. La démarche de calcul est présentée avec l’exemple d’un échantillon de mousse. Une première phase de prédéformation est effectuée en utilisant des essais de compression décompression comme données d’entrée. Une fois cette étape validée, le calcul dynamique est réalisé. Deux modèles matériaux sont comparés et montrent les limites de la modélisation actuelle