A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation:Association of Gut Microbiota With Liver Inflammation

BACKGROUND: Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis, the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. Cytochrome P4502D6 (CYP2D6) is the antigenic target of anti-LKM1 and formiminotransferase cyclodeaminase (FTCD) is the antigenic target of anti-LC1. It is known that AIH, both type-1 and type-2, is strongly linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. However, the direct evidence of the association of HLA with AIH is lacking. METHODS: We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the non-obese diabetic (NOD) background (HLA-DR3 NOD) by immunization of HLA-DR3(−) and HLA-DR3(+) NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein. RESULTS: Immunization with CYP2D6/FTCD leads to a sustained elevation of alanine aminotransferase (ALT), development of ANA and anti-LKM1/anti-LC1 autoantibodies, chronic immune cell infiltration and parenchymal fibrosis on liver histology in HLA-DR3(+) mice. Immunized mice also showed an enhanced Th1 immune response and paucity of the frequency of regulatory T-cell (Treg) in the liver. Moreover, HLA-DR3(+) mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. CONCLUSION: Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo

Formation of Additive-Containing Nanothermites and Modifications to their Friction Sensitivity

<p>Nanothermites can provide high energy densities and reaction rates but can also display extreme friction sensitivities. Additives that provide friction modification offer the potential to reduce the friction sensitivity of nanothermites. In the present work, MoS₂, graphene, and hexadecane additives were dispersed in MoO₃ prior to nanothermite formation with the aim of reducing friction sensitivity. Nanothermites were subsequently prepared using a palmitic acid–passivated nano-aluminum (L-Al) and additive-containing nano-MoO₃ by the resonant acoustic mixing of dry powders. In general, the incorporation of additives results in a reduction in friction sensitivity with the baseline minimum ignition friction rising from 10 to 120 N using 0.5% wt/wt micrometer-sized MoS₂ or 5% wt/wt hexadecane. However, the relationships between loading and performance are complex and vary by additive; for example, the friction sensitivity dependence using micrometer-diameter MoS₂ displays a maximum at 0.5% wt/wt and declines to 7 N using 5% MoS₂.</p

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EVALUATION OF GIM AS A GREENER INSENSITIVE MELT-CAST EXPLOSIVE

For years, DRDC Valcartier has invested efforts at developing energetic thermoplastic elastomers (ETPEs) based on linear glycidyl azide polymers to serve as energetic binders and replacing the thermoset matrix in insensitive explosives. It was first observed that introducing ETPEs in their melted form was not an easy task because high and nonpractical viscosities were encountered in the process. It was discovered that 2,4,6-trinitrotoluene (TNT) could be used in its melted form as an organic solvent to dissolve the ETPE and allow its incorporation into the insensitive formulations. Using these ETPEs led to the development of a greener insensitive melt-cast explosive named green insensitive munitions (GIM). This new explosive was intensely studied. The mechanical properties and proportions of ETPE in the formulations were optimized to obtain a melt cast with low viscosity while leading to an insensitive explosive formulation. Work was conducted on GIM explosives to test their performance and sensitivity, fate and behavior with regard to the environment, their recycling capability, and toxicity. This paper describes the results of all experiments conducted so far to test these aspects of GIM explosives. The preparation of the ETPEs and the GIM explosives will also be briefly described

Standardisation of methods in soil microbiology: progress and challenges

International audienceA plethora of methods have been developed over the few last decades to enable a better understanding of the ecology of soil microbial communities and their roles in soil functioning. However, there is generally considerable variation (both subtle and more extensive) in the actual realisation of these methods, and limited efforts have been devoted to their standardisation, despite this being crucial to underpin data comparison and integration. Ensuring comparable data across studies through standardisation is arguably best-practice, as well as necessary to effectively meet the objectives of various schemas, which require assessment of the consequences of the global change and intensification of human activities on the functioning of the soil ecosystem and its biological diversity. This article presents an overview of the existing and forthcoming ISO standards in soil microbiology and highlights possible future research efforts to be undertaken for developing new standards. We also discuss some practical and theoretical bottlenecks and hurdles that have limited standardisation in soil microbiology up to now