Interferon-alpha reduces human hippocampal neurogenesis and increases apoptosis via activation of distinct STAT1-dependent mechanisms

BACKGROUND: In humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis. METHODS: We used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis. RESULTS: Both concentrations of interferon-α decreased hippocampal neurogenesis, with the high concentration also increasing apoptosis. Moreover, interferon-α increased the expression of interferon-stimulated gene 15 (ISG15), ubiquitin-specific peptidase 18 (USP18), and interleukin-6 (IL-6) via activation of STAT1. Like interferon-α, co-treatment with a combination of ISG15, USP18, and IL-6 was able to reduce neurogenesis and enhance apoptosis via further downstream activation of STAT1. Further experiments showed that ISG15 and USP18 mediated the interferon-α-induced reduction in neurogenesis (potentially through upregulation of the ISGylation-related proteins UBA7, UBE2L6, and HERC5), while IL-6 mediated the interferon-α-induced increase in apoptosis (potentially through downregulation of aquaporin 4). Using transcriptomic analyses, we showed that interferon-α regulated pathways involved in oxidative stress and immune response (e.g., Nuclear Factor (erythroid-derived 2)-like 2 [Nrf2] and interferon regulatory factor [IRF] signaling pathway), neuronal formation (e.g., CAMP response element-binding protein [CREB] signaling), and cell death regulation (e.g., tumor protein(p)53 signaling). CONCLUSIONS: We identify novel molecular mechanisms mediating the effects of interferon-α on the human hippocampus potentially involved in inflammation-induced neuropsychiatric symptoms

Le Rat (nouvel animal de compagnie)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Vers une agriculture sans ruralité ? La renégociation de la place de l’agriculture sur l’île de Bréhat (xxe-xxie siècle)

International audienceDistribution électronique Cairn.info pour Presses universitaires de Rennes. © Presses universitaires de Rennes. Tous droits réservés pour tous pays. La reproduction ou représentation de cet article, notamment par photocopie, n'est autorisée que dans les limites des conditions générales d'utilisation du site ou, le cas échéant, des conditions générales de la licence souscrite par votre établissement. Toute autre reproduction ou représentation, en tout ou partie, sous quelque forme et de quelque manière que ce soit, est interdite sauf accord préalable et écrit de l'éditeur, en dehors des cas prévus par la législation en vigueur en France. Il est précisé que son stockage dans une base de données est également interdit

Elaboration et caractérisation de céramiques et de cermets à base de TiB2

Nous avons étudié la densification de céramiques et de cermets à base de TiB2 et les propriétés mécaniques en relation avec la microstructure. On a étudié les facteurs les plus influençant : la taille de grains, les activateurs de frittage, la température de frittage et les techniques de densification comme le pressage uniaxial à chaud (HP) ou le pressage isostatique à chaud (HIP). L objectif de ce travail est le développement de matériaux, usinables par électroérosion, présentant une dureté Hv > 1500 Hv et une ténacité KIC > 8 MPa.m1/2, pour des applications industrielles types outils de coupe ou pièces mécaniques résistantes en usure. Dans un premier temps, on a étudié l effet de la température et de la taille de particules sur la densification par HP et par HIP et les propriétés mécaniques de céramiques à base TiB2. En frittant par HP, on obtient les meilleures propriétés pour une températures de frittage de 1990 C, avec un taux de densification de 99.3 % et une dureté de 2600 Hv pour une poudre initiale de taille de particules de 6.8 m. Toutefois, on constate une croissance de grains importante, ce qui produit une diminution de la contrainte à la rupture. La mauvaise densification obtenue pour la poudre fine s explique par un pourcentage d oxygène élevé (2 % en masse). En revanche, la densification par HIP permet de diminuer la température optimale de frittage à 1800 C et de limiter ainsi la croissance de grains. Le meilleur résultat est toujours obtenu pour la poudre à 6.8 m, avec 100 % de densification et une dureté de 2650 Hv. La deuxième phase de l étude, concerne l effet de l ajout d un activateur de frittage (B4C) et de la taille des particules de poudres. Dans une première approche, on a réalisé une étude sur la poudre à 12 m pour différentes pourcentage de B4C, un optimum a été obtenu à 10 % en masse. On a ensuite réalisé un composite similaire avec la poudre à 6.8 m. Une très bonne répartition de la phase B4C et l homogénéité de la microstructure ont conduit à une densification et dureté élevées (99.8 % et 2500 Hv) et une contrainte à la rupture de plus de 400 MPa, cependant la ténacité est de l ordre de 6.6 MPa.m1/2. Afin d augmenter la ténacité du TiB2, on a étudié, dans la deuxième partie, l effet de l ajout d une phase liante métallique pour former un cermet. Ces matériaux composés d une céramique et d un métal présentent des propriétés issues d un compromis entre la dureté de l une et la ténacité de l autre. On a choisi d utiliser le Ni3Al comme liant intermétallique pour ces propriétés intermédiaires entre les céramiques et les métaux. Cet intermétallique n étant pas disponible dans le commerce, on a procédé de deux manières pour le former : La voie indirecte, consiste à le synthétiser à partir d un mélange Ni et Al, puis l introduire dans la matrice TiB2. On a constaté après frittage une réaction entre le bore libre issu de la dissolution du TiB2 et la phase liante. Un borure secondaire s est formé, produisant la diminution de la résistance du cermet. La voie directe, consiste à introduire le Ni et le TiAl3, correspondant à 20 % en volume de liant, dans la matrice TiB2. Le traitement thermique de ce mélange permet de former une phase Ni3(Al,Ti) en équilibre avec TiB2. Un post-hipping permet de compléter la densification du cermet et d améliorer les propriétés mécaniques (Hv = 1610 et KIC = 10.8 MPa.m1/2). Des essais tribologiques ont été réalisés sur les matériaux les plus intéressants, afin de mesurer leur taux d usure pour un frottement sans lubrification. Le cermet après post hipping et le composite avec la poudre à 12 m présentent la plus faible usure. Aussi, les matériaux ont été optimisés en usinage par EDM en améliorant leur état de surface. Enfin, des prototypes de filières d extrusion ont été testés sur une chaîne de production. Compte tenu de la sévérité des essais, on a conclu que le composites présentent un bon comportement en usure. Ce travail a été réalisé dans le cadre du projet européen Moncerat , avec la participation de plusieurs industriels et laboratoires.This work is done in the framework of Moncenat European project, with the participation of severals industrials and laboratories. The aim is the development of ceramics machinable per EDM, with hardness Hv &gt 1500 Hv and toughness KIC&gt8 Mpa.m^1/2, for applications as cutting tools or mechanical resistant parts in wear. The densification and the mechanical properties of TiB2 based ceramics and cermets have been studied with their relation with the microstructure. We have studied the most influent factors : grain size, sintering additives, sintering temperature and densification technique as hot pressing (HP) and hot isostatic pressing (HIP). In order to increase TiB2 toughness, we have studied intermetallic binder phase (Ni3Al) effect to form cermet. This materials elaborated from ceramic and metal, show properties coming from a compromise between hardness of ceramic and toughness of metal. Tribological tests have been performed in the most interesting materials. Likewise, the materials have been optimised in EDM machining with improving surface quality. At last, extrusion dies prototypes have been tested in line production. Interesting results have been obtained concerning composites materials.VILLEURBANNE-DOC'INSA LYON (692662301) / SudocSudocFranceF

Microstructure and mechanical properties of TiC-TiN based cermets for tools application

International audienceThe objective of this work is to develop materials with both a good hardness and a good toughness. Titanium carbonitride has a significant hardness (2000Hv), but its toughness (6 MPa√m) is insufficient for tools applications. Toughness can be improved by addition of a metallic binder. Cermets based on TiC and TiN with Ni as binder are the most developed materials. In the present work, the effect of TiN addition and binder content on the microstructure and the properties of the TiC based cermets elaborated by pressureless sintering have been investigated. Results show that dense cermets with specific core/rim structure have been obtained. The rupture strength and the toughness increase with the addition of Ni. The optimum values of mechanical properties were found for the cermet with 15 wt% Ni and 10 wt% TiN addition, respectively, which exhibits a Vickers hardness over 1400 Hv0.3 and a fracture toughness around 13.6 MPa√m

Influence of crystallinity on thermo-process ability and mechanical properties in a Au-based bulk metallic glass

cited By 2International audienceThe present investigation addresses the impact of crystallinity on the mechanical properties: hardness (HV) and toughness (KIC) in an Au49Cu26.9Ag5.5Pd2.3Si16.3 BMG which appears especially attractive for applications in jewelry and watch making industries. Thermal stability is first determined using differential scanning calorimetry (DSC), X-ray diffraction and thermo-mechanical analysis (TMA). Then the conditions (time, temperature) in which crystallization is observed (during annealing above the glass transition temperature) and the kinetics are determined. Results show an increase of hardness proportional to the volume fraction of the crystalline phase (φ) (from about 350 HV up to about 480 HV), and a drastic reduction in fracture toughness from about 20 MPa√m down to 1.5 MPa√m for fully crystalline structure. Finally the conditions required achieving a good compromise between hardness and toughness are established. © 2016 Elsevier B.V

Insight on the process ability of bulk metallic glasses by thermo-mechanical analysis and dynamic mechanical analysis

cited By 6International audienceMechanical properties of glassy materials exhibit drastic changes in the supercooled liquid region (SLR). In the current research, mechanical properties in several typical bulk metallic glasses (Pd42.5Ni7.5Cu30P20, Zr56Co28Al16 and Zr58Nb3Cu16Ni13Al10) were measured using both dynamic mechanical analysis and thermo-mechanical analysis. The modifications of elastic modulus (determined by dynamic mechanical analysis) and viscosity (determined by thermo-mechanical analysis) are strongly connected. The experimental findings suggest that the elastic modulus of the bulk metallic glasses evaluated by dynamic mechanical analysis correlates with the length variations determined by thermo-mechanical analysis facilities. Evidences from the experiments demonstrate that the modifications are very important in the bulk metallic glass with a large supercooled region and a large fragility, (Pd42.5Ni7.5Cu30P20), very limited in the bulk metallic glass with a limited supercooled region and a small fragility (Zr56Co28Al16), intermediate in the third case (Zr58Nb3Cu16Ni13Al10). The onset of crystallization corresponds to the end of the deformation of the sample and to the onset of the hardness increase. Therefore, these two different techniques (dynamic mechanical analysis and thermo-mechanical analysis) can provide useful and insightful information on the process ability of these amorphous materials. © 2015 Elsevier B.V. All rights reserved

Bulk metallic glasses based on precious metals: Thermal treatments and mechanical properties

cited By 6International audienceThe thermomechanical behavior of precious based metallic glasses has been investigated. Their compositions are free of nickel for biocompatibility. The gold-based BMG has a gold content resulting in 18 Karats alloy, a supercooled liquid region of 43 °C and a casting diameter up to 5 mm in rod. The compositions of platinum and palladium based BMGs are interesting as they can be formed into bulk glassy rods with diameter up to 15 and 30 mm respectively. The platinum-based BMG has a platinum content resulting in 850 Pt grade with a supercooling region reaching 58 °C. The palladium-based BMG is principally composed of 40 wt.% palladium and 32 wt.% platinum, with a large supercooling region reaching 73 °C. The thermoplastic deformation of these BMG has been examined using thermomechanical analyser (TMA) and the results show that the alloys can be easily processed in the supercooled liquid region. During thermal processing, crystallization must be controlled since it improves hardness and elastic modulus, but embrittles the alloys and stops the deformation. The high hardness of Au-, Pt- and Pd- base BMGs (respectively 340, 420, 460 HV) twice the value of conventional precious metals, coupled with good properties for superplastic forming in the supercooled liquid region made them promising materials for watch making and jewelry applications. © 2015 Elsevier Ltd. All rights reserved

Hot pressed titanium nitride obtained from SHS starting powders: Influence of a pre-sintering heat-treatment of the starting powders on the densification process

International audienceSynthesis of titanium nitride (TiN) powders by the self propagating high temperature synthesis (SHS) process is economically appealing. This chemical reaction allows producing fine grains powders with a high specific surface area (12 m2/g). After a thermal treatment above 1000 °C under argon atmosphere, the physical and microstructural characteristics of the powders are drastically modified: density increases and specific surface decreases. Powders morphology and heat treatment influence are investigated by transmission electron microscopy. Observations reveal a regular nanocrystalline layer, surrounding the particles. After heat treatment, this layer disappears from grains surface and powders undergo important morphological changes. The behavior of these special ceramic powders during the sintering stage by the hot press process is investigated. Bulk specimens obtained are characterized from a physical, microstructural and mechanical point of view and the beneficial effect of the heat treatment on starting powder is explained. Bulk specimens processed in the optimum conditions reach a relative density superior to 98%, a microhardness of 1790 Hv and a Young modulus of 430 MPa