Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release.

Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA immune sensors but rather the DNA sensor cGAS and the prevalence of mitochondrial DNA (mtDNA) in the cytoplasm.

FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction.

The mitochondrial integrated stress response (mitoISR) has emerged as a major adaptive pathway to respiratory chain deficiency, but both the tissue specificity of its regulation, and how mitoISR adapts to different levels of mitochondrial dysfunction are largely unknown. Here, we report that diverse levels of mitochondrial cardiomyopathy activate mitoISR, including high production of FGF21, a cytokine with both paracrine and endocrine function, shown to be induced by respiratory chain dysfunction. Although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of mitoISR.

Identification of the Beagle 2 lander on Mars.

The 2003 Beagle 2 Mars lander has been identified in Isidis Planitia at 90.43° E, 11.53° N, close to the predicted target of 90.

Bias in Point Estimates and Standard Errors of Mokken's Scalability Coefficients.

Mokken scale analysis uses three types of scalability coefficients to assess the quality of (a) pairs of items, (b) individual items, and (c) an entire scale. Both the point estimates and the standard errors of the scalability coefficients assume that the sample ordering of the item steps is identical to the population ordering, but due to sampling error, the sample ordering may be incorrect and, consequently, the estimates and the standard errors may be biased. Two simulation studies were used to investigate the bias of the estimates and the standard errors of the scalability coefficients, as well as the coverage of the 95% confidence intervals.