Experimental infection of Foxes with European bat Lyssaviruses type-1 and 2

<p>Abstract</p> <p>Background</p> <p>Since 1954, there have been in excess of 800 cases of rabies as a result of European Bat <it>Lyssaviruses </it>types 1 and 2 (EBLV-1, EBLV-2) infection, mainly in Serotine and Myotis bats respectively. These viruses have rarely been reported to infect humans and terrestrial mammals, as the only exceptions are sheep in Denmark, a stone marten in Germany and a cat in France. The purpose of this study was to investigate the susceptibility of foxes to EBLVs using silver foxes (<it>Vulpes vulpes</it>) as a model.</p> <p>Results</p> <p>Our experimental studies have shown that the susceptibility of foxes to EBLVs is low by the intramuscular (IM) route, however, animals were sensitive to intracranial (IC) inoculation. Mortality was 100% for both EBLV-1 (~4.5 logs) and EBLV-2 (~3.0 logs) delivered by the IC route. Virus dissemination and inflammatory infiltrate in the brain were demonstrated but virus specific neutralising antibody (VNA) was limited (log(ED₅₀) = 0.24–2.23 and 0.95–2.39 respectively for specific EBLV-1 and EBLV-2). Foxes were also susceptible, at a low level, to peripheral (IM) infection (~3.0 logs) with EBLV-1 but not EBLV-2. Three out of 21 (14.3%) foxes developed clinical signs between 14 and 24 days post-EBLV-1 infection. None of the animals given EBLV-2 developed clinical disease.</p> <p>Conclusion</p> <p>These data suggest that the chance of a EBLV spill-over from bat to fox is low, but with a greater probability for EBLV-1 than for EBLV-2 and that foxes seem to be able to clear the virus before it reaches the brain and cause a lethal infection.</p

Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target

Ongoing developments in sporadic inclusion body myositis

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM

Tubular Aggregates and Cylindrical Spirals Have Distinct Immunohistochemical Signatures

Tubular aggregates and cylindrical spirals are 2 distinct ultrastructural abnormalities observed in muscle biopsies that have similar histochemical staining characteristics on light microscopy. Both are found in a wide range of disorders. Recently, a number of genetic mutations have been reported in conditions with tubular aggregates in skeletal muscle. It is widely accepted that tubular aggregates arise from the sarcoplasmic reticulum, but the origin of cylindrical spirals has been less clearly defined. We describe the histopathological features of myopathies with tubular aggregates, including a detailed immunohistochemical analysis of congenital myasthenic syndromes with tubular aggregates due to mutations in GFPT1 and DPAGT1, and myopathies with cylindrical spirals. Our findings support the notion that cylindrical spirals, like tubular aggregates, derive primarily from the sarcoplasmic reticulum; however, immunohistochemistry indicates that different molecular components of the sarcoplasmic reticulum may be involved and can be used to distinguish between these different inclusions. The immunohistochemical differences may also help to guide genetic testing

Post Celtic Tiger Ireland: Exploring New Cultural Spaces

International audienceThis collective volume provides the reader with an exploration of various artistic works which grew out of the post-Celtic Tiger era in Ireland. The different cultural fields of interest studied in this book include theatre, photography, poetry, painting, and cinema, as well as commemorative spaces. These different cultural voices explore Ireland, as a country located at a crossroads in a kind of in-between space, and to examine these fields and the associated political, economic, historical and social forces present in the country. These contributions interrogate Irish society within its present context, which is deeply impregnated by movement and transition, but also strongly connected to time, to past and to memory. This collection of essays also presents the way in which these artistic works shed light on the transformations induced by both the Celtic Tiger and its aftermath. The issues of globalisation, identity, place and creativity are all dealt with. In assessing the aftermath of the post-Celtic Tiger period and its impact and influences on today’s Irish society through some of its cultural productions, our contributors also allude, incidentally, to its future

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