Chemotactic and Inflammatory Responses in the Liver and Brain Are Associated with Pathogenesis of Rift Valley Fever Virus Infection in the Mouse

Rift Valley fever virus (RVFV) is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that might survive the initial hepatitis is neurologic in nature which is supported by observations of human disease and the BALB/c mouse model

Functionalization of biomaterials for joint implant application

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High resolution transmission electron microscopy study of quasi-amorphous MoSx coatings

Thin MoSx (x=1.2) films are deposited on 440C steel or Si by ion beam sputtering of an MoS2 target with (or without) high energy (160 keV) Ar+ ion beam assistance. The coating microstructures of the as-deposited films are analyzed by high resolution transmission electron microscopy (HRTEM). HRTEM images of the sputter-deposited MoSx films show domains with few fringes roughly parallel to the substrate, embedded in a typical amorphous structure. This confirms the suggestion made in a previous publication that these sputtered films are amorphous with short-range order in the form of layered clusters with layers parallel to the substrate. The HRTEM images of the ion-beam assisted films show small crystallites (with no preferential orientation) within an amorphous structure. The difference between the tribological properties of these two types of coating is explained by the difference in their microstructures. HRTEM study of the wear track microstructures shows the important role played by the layered clusters which form an interfacial film accommodating sliding motion

Strains in thermally growing Cr2O3 films measured in situ using synchrotron X-rays

International audienceThis work takes place in the general context of a better understanding of materials degradation mechanisms in extreme environments. In particular, the aim of the present study was to correlate microstructural elements to growth stress magnitude evolution and stress release mechanisms for thermally grown chromia thin films on NiCr alloys. Strains in thermally grown oxides have been measured in-situ, as the oxides develop and evolve. Data have been acquired from oxides grown for different high temperatures evolutions on NiCr model alloys that form Cr2O3. Using synchrotron X-Ray at the ESRF (Beamline BM02) coupled with an induction furnace, Debye-Scherrer diffraction patterns from the oxidizing specimen were recorded in air at temperature between 700-1000°C and during cooling. The distortion of the diffraction rings was analyzed to yield the in-plane strain. Thermal stresses imposed on Cr2O3/NiCr by abruptly reducing the sample temperature for a period of time, exploiting the thermal expansion difference between oxide and substrate, showed noticeable subsequent stress relaxation by creep. Such a mechanism was monitored using time-dependent in situ measurements of strain relaxation in the oxide. The main results obtained from these experiments are the kinetic of the growth stress from the isothermal measurements (isothermal plateau), and the study of the stress release mechanism after the low-temperature jumps. In complement, the oxide microstructure development during the course of oxidation is also investigated from both the peaks intensity and width evolution. In all cases, the steady stage growth strain was relatively low and compressive. Different degrees of relaxation were also found on cooling depending on scale microstructure through the variation of the initial oxidation conditions. Results are compared with other reports of residual stresses evolution in Cr2O3 scales. © 2017 Trans Tech Publications, Switzerland

Calpain 3: a key regulator of the sarcomere?

International audienceCalpain 3 is a 94-kDa calcium-dependent cysteine protease mainly expressed in skeletal muscle. In this tissue, it localizes at several regions of the sarcomere through binding to the giant protein, titin. Loss-of-function mutations in the calpain 3 gene have been associated with limb-girdle muscular dystrophy type 2A (LGMD2A), a common form of muscular dystrophy found world wide. Recently, significant progress has been made in understanding the mode of regulation and the possible function of calpain 3 in muscle. It is now well accepted that it has an unusual zymogenic activation and that cytoskeletal proteins are one class of its substrates. Through the absence of cleavage of these substrates, calpain 3 deficiency leads to abnormal sarcomeres, impairment of muscle contractile capacity, and death of the muscle fibers. These data indicate a role for calpain 3 as a chef d'orchestre in sarcomere remodeling and suggest a new category of LGMD2 pathological mechanisms