ASC filament formation serves as a signal amplification mechanism for inflammasomes

A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). Here we show that assembly of the ASC speck involves oligomerization of ASC(PYD) into filaments and cross-linking of these filaments by ASC(CARD). ASC mutants with a non-functional CARD only assemble filaments but not specks, and moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis of ASC(PYD) is used to identify oligomerization-deficient ASC mutants and demonstrate that ASC speck formation is required for efficient processing of IL-1β, but dispensable for gasdermin-D cleavage and pyroptosis induction. Our results suggest that the oligomerization of ASC creates a multitude of potential caspase-1 activation sites, thus serving as a signal amplification mechanism for inflammasome-mediated cytokine production

Muscle dysmorphia research neglects DSM-5 diagnostic criteria

This systematic review aimed to collect, evaluate, and synthesize the research on muscle dysmorphia (MD) post official recognition as a specifier for body dysmorphic disorder (BDD) in the DSM-5, and provide recommendations for future research. Literature searches were conducted in four databases to see if inclusion criteria were met. Results revealed 33 studies meeting inclusion criteria, none of which utilized DSM-5 criteria for MD and/or acknowledged the criterion in their research. Few studies acknowledged the association between MD and BDD, and the methodological quality of recent MD research was considered low due to a lack of clinical samples, measurements not using validated cut-off scores, and the research designs. In conclusion, future MD research is encouraged to utilize DSM-5 diagnostic criteria to better inform clinical practice; and significantly improve the methodological quality. As such, more effective treatment options may be developed reducing the risk of health harming consequences in these individuals

On the Observability of Giant Protoplanets in Circumstellar Disks

We investigate the possibility to detect giant planets that are still embedded in young circumstellar disks. Based on models with different stellar, planetary, and disk masses, and different radial positions of the planet we analyze the resulting submillimeter appearance of these systems. We find that the influence of the planet on the spectral energy distribution could not be distinguished from that of other disk parameters. However, dust reemission images of the disks show that the hot region in the proximity of a young planet, along with the gap, could indeed be detected and mapped with the Atacama Large Millimeter Array in the case of nearby circumstellar disks (d<100pc) in approximate face-on orientation.Comment: ApJ, in pres

Cardiovascular ephrinB2 function is essential for embryonic angiogenesis

EphrinB2, a transmembrane ligand of EphB receptor tyrosine kinases, is specifically expressed in arteries. In ephrinB2 mutant embryos, there is a complete arrest of angiogenesis. However, ephrinB2 expression is not restricted to vascular endothelial cells, and it has been proposed that its essential function may be exerted in adjacent mesenchymal cells. We have generated mice in which ephrinB2 is specifically deleted in the endothelium and endocardium of the developing vasculature and heart. We find that such a vascular-specific deletion of ephrinB2 results in angiogenic remodeling defects identical to those seen in the conventional ephrinB2 mutants. These data indicate that ephrinB2 is required specifically in endothelial and endocardial cells for angiogenesis, and that ephrinB2 expression in perivascular mesenchyme is not sufficient to compensate for the loss of ephrinB2 in these vascular cells