Focal Contacts as Mechanosensors: Externally Applied Local Mechanical Force Induces Growth of Focal Contacts by an Mdia1-Dependent and Rock-Independent Mechanism

The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force

Skeletal-Muscle Glutamine Synthase is Upregulated in Preclinical Prion Diseases

In prion diseases, aggregates of misfolded prion protein (PrP$^{Sc}$) accumulate not only in the brain but can also be found in various extraneural tissues. This raises the question whether prion-specific pathologies arise also in these tissues. Here we sequenced mRNA transcripts in skeletal muscle, spleen and blood of prion-inoculated mice at eight timepoints during disease progression. We detected consistent gene-expression changes in all three organs, with skeletal muscle showing the most uniform alterations during disease progression. The glutamate synthetase (GLUL) gene was monotonically upregulated in skeletal muscle of mice infected with three different scrapie prion strains (RML, ME7 and 22L) and in human sporadic Creutzfeldt-Jakob disease. GLUL dysregulation was accompanied by changes in glutamate/glutamine metabolism, leading to reduced glutamate levels in skeletal muscle. None of these changes were observed in skeletal muscle of humans with amyotrophic lateral sclerosis, Alzheimer’s disease, or dementia with Lewy bodies, suggesting that they are specific to prion diseases. Besides pointing to unrecognized metabolic implications of prion infections, these findings suggest that GLUL could represent an accessible biomarker of prion disease progression, particularly during the preclinical stages of disease, and might be useful for monitoring the efficacy of experimental antiprion therapies

Use of complementary and alternative medicine by those with a chronic disease and the general population - results of a national population based survey

<p>Abstract</p> <p>Background</p> <p>The use of complementary and alternative medicine (CAM) is becoming more common, but population-based descriptions of its patterns of use are lacking. This study aimed to determine the prevalence of CAM use in the general population and for those with asthma, diabetes, epilepsy and migraine.</p> <p>Methods</p> <p>Data from cycles 1.1, 2.1 and 3.1 of the Canadian Community Health Survey (CCHS) were used for the study. The CCHS is a national cross-sectional survey administered to 400,055 Canadians aged ≥12 between 2001-2005. Self-reported information about professionally diagnosed health conditions was elicited. CCHS surveys use a multistage stratified cluster design to randomly select a representative sample of Canadian household residents. Descriptive data on the utilization of CAM services was calculated and logistic regression was used to determine what sociodemographic factors predict CAM use.</p> <p>Results</p> <p>Weighted estimates show that 12.4% (95% Confidence Interval (CI): 12.2-12.5) of Canadians visited a CAM practitioner in the year they were surveyed; this rate was significantly higher for those with asthma 15.1% (95% CI: 14.5-15.7) and migraine 19.0% (95% CI: 18.4-19.6), and significantly lower for those with diabetes 8.0% (95% CI: 7.4-8.6) while the rate in those with epilepsy (10.3%, 95% CI: 8.4-12.2) was not significantly different from the general population.</p> <p>Conclusion</p> <p>A large proportion of Canadians use CAM services. Physicians should be aware that their patients may be accessing other services and should be prepared to ask and answer questions about the risks and benefits of CAM services in conjunction with standard medical care.</p

The 2015 Annual Meeting of SETAC German Language Branch in Zurich (7-10 September, 2015): ecotoxicology and environmental chemistry-from research to application

This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1