9 research outputs found
The ER-Bound RING Finger Protein 5 (RNF5/RMA1) Causes Degenerative Myopathy in Transgenic Mice and Is Deregulated in Inclusion Body Myositis
Growing evidence supports the importance of ubiquitin ligases in the pathogenesis of muscular disorders, although underlying mechanisms remain largely elusive. Here we show that the expression of RNF5 (aka RMA1), an ER-anchored RING finger E3 ligase implicated in muscle organization and in recognition and processing of malfolded proteins, is elevated and mislocalized to cytoplasmic aggregates in biopsies from patients suffering from sporadic-Inclusion Body Myositis (sIBM). Consistent with these findings, an animal model for hereditary IBM (hIBM), but not their control littermates, revealed deregulated expression of RNF5. Further studies for the role of RNF5 in the pathogenesis of s-IBM and more generally in muscle physiology were performed using RNF5 transgenic and KO animals. Transgenic mice carrying inducible expression of RNF5, under control of β-actin or muscle specific promoter, exhibit an early onset of muscle wasting, muscle degeneration and extensive fiber regeneration. Prolonged expression of RNF5 in the muscle also results in the formation of fibers containing congophilic material, blue-rimmed vacuoles and inclusion bodies. These phenotypes were associated with altered expression and activity of ER chaperones, characteristic of myodegenerative diseases such as s-IBM. Conversely, muscle regeneration and induction of ER stress markers were delayed in RNF5 KO mice subjected to cardiotoxin treatment. While supporting a role for RNF5 Tg mice as model for s-IBM, our study also establishes the importance of RNF5 in muscle physiology and its deregulation in ER stress associated muscular disorders
Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice
Federal Oversight, State Policy Making, and the Courts: An Empirical Analysis of Nursing Facility Litigation Under the Boren Amendment
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Climate, Ticks and Disease
This book brings together expert opinions from scientists to consider the evidence for climate change and its impacts on ticks and tick-borne infections. It considers what is meant by 'climate change', how effective climate models are in relation to ecosystems, and provides predictions for changes in climate at global, regional and local scales relevant for ticks and tick-borne infections. It examines changes to tick distribution and the evidence that climate change is responsible. The effect of climate on the physiology and behaviour of ticks is stressed, including potentially critical impacts on the tick microbiome. Given that the notoriety of ticks derives from pathogens they transmit, the book considers whether changes in climate affect vector capacity. Ticks transmit a remarkable range of micro- and macro-parasites many of which are pathogens of humans and domesticated animals. The intimacy between a tick-borne agent and a tick vector means that any impacts of climate on a tick vector will impact tick-borne pathogens. Most obviously, such impacts will be apparent as changes in disease incidence and prevalence. The evidence that climate change is affecting diseases caused by tick-borne pathogens is considered, along with the potential to make robust predictions of future events. This book contains: Expert opinions and predictions. Global coverage of trends in ticks and disease. In-depth examination of climate change and tick distribution links.This book is suitable for researchers and students studying zoology, biological sciences, medical entomology, animal health, veterinary medicine, epidemiology, parasitology, and climate change impacts; and for those concerned with public health planning or livestock management where ticks and tick-borne pathogens pose a threat