Current Pathophysiological and Genetic Aspects of Dilated Cardiomyopathy

Dilated cardiomyopathy is the most common form of cardiomyopathy and the second leading cause of left ventricular dysfunction with highly variable clinical presentation and prognosis. The clinical courses vary and are strongly heterogeneous, ranging from asymptomatic patients to those suffering from intractable heart failure or sudden cardiac death due to arrhythmias. Previous studies have reported a 10 years cardiovascular mortality up to 40% in developed countries, due to advanced heart failure or sudden cardiac death. However, the prognosis of dilated cardiomyopathy patients is variable and depends on multiple risk factors. This chapter provides a review of dilated cardiomyopathy with specific focus on the pathophysiological aspects and genetic etiology of the disease

CfA3: 185 Type Ia Supernova Light Curves from the CfA

We present multi-band photometry of 185 type-Ia supernovae (SN Ia), with over 11500 observations. These were acquired between 2001 and 2008 at the F. L. Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics (CfA). This sample contains the largest number of homogeneously-observed and reduced nearby SN Ia (z < 0.08) published to date. It more than doubles the nearby sample, bringing SN Ia cosmology to the point where systematic uncertainties dominate. Our natural system photometry has a precision of 0.02 mag or better in BVRIr'i' and roughly 0.04 mag in U for points brighter than 17.5 mag. We also estimate a systematic uncertainty of 0.03 mag in our SN Ia standard system BVRIr'i' photometry and 0.07 mag for U. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars, where available for the same SN, reveal agreement at the level of a few hundredths mag in most cases. We find that 1991bg-like SN Ia are sufficiently distinct from other SN Ia in their color and light-curve-shape/luminosity relation that they should be treated separately in light-curve/distance fitter training samples. The CfA3 sample will contribute to the development of better light-curve/distance fitters, particularly in the few dozen cases where near-infrared photometry has been obtained and, together, can help disentangle host-galaxy reddening from intrinsic supernova color, reducing the systematic uncertainty in SN Ia distances due to dust.Comment: Accepted to the Astrophysical Journal. Minor changes from last version. Light curves, comparison star photometry, and passband tables are available at http://www.cfa.harvard.edu/supernova/CfA3

Vibrio cholerae evades neutrophil extracellular traps by the activity of two extracellular nucleases

The Gram negative bacterium Vibrio cholerae is the causative agent of the secretory diarrheal disease cholera, which has traditionally been classified as a noninflammatory disease. However, several recent reports suggest that a V. cholerae infection induces an inflammatory response in the gastrointestinal tract indicated by recruitment of innate immune cells and increase of inflammatory cytokines. In this study, we describe a colonization defect of a double extracellular nuclease V. cholerae mutant in immunocompetent mice, which is not evident in neutropenic mice. Intrigued by this observation, we investigated the impact of neutrophils, as a central part of the innate immune system, on the pathogen V. cholerae in more detail. Our results demonstrate that V. cholerae induces formation of neutrophil extracellular traps (NETs) upon contact with neutrophils, while V. cholerae in return induces the two extracellular nucleases upon presence of NETs. We show that the V. cholerae wild type rapidly degrades the DNA component of the NETs by the combined activity of the two extracellular nucleases Dns and Xds. In contrast, NETs exhibit prolonged stability in presence of the double nuclease mutant. Finally, we demonstrate that Dns and Xds mediate evasion of V. cholerae from NETs and lower the susceptibility for extracellular killing in the presence of NETs. This report provides a first comprehensive characterization of the interplay between neutrophils and V. cholerae along with new evidence that the innate immune response impacts the colonization of V. cholerae in vivo. A limitation of this study is an inability for technical and physiological reasons to visualize intact NETs in the intestinal lumen of infected mice, but we can hypothesize that extracellular nuclease production by V. cholerae may enhance survival fitness of the pathogen through NET degradation