ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1)

The metalloprotease ADAM17 (a disintegrin and metalloprotease 17) is a key regulator of tumor necrosis factor ? (TNF?), interleukin 6 receptor (IL-6R), and epidermal growth factor receptor (EGFR) signaling. ADAM17 maturation and function depend on the seven-membrane?spanning inactive rhomboid-like proteins 1 and 2 (iRhom1/2 or Rhbdf1/2). Most studies to date have focused on overexpressed iRhom1 and -2, so only little is known about the properties of the endogenous proteins. Here, we show that endogenous iRhom1 and -2 can be cell surface?biotinylated on mouse embryonic fibroblasts (mEFs), revealing that endogenous iRhom1 and -2 proteins are present on the cell surface and that iRhom2 also is present on the surface of lipopolysaccharide-stimulated primary bone marrow?derived macrophages. Interestingly, very little, if any, iRhom2 was detectable in mEFs or bone marrow?derived macrophages lacking ADAM17, suggesting that iRhom2 is stabilized by ADAM17. By contrast, the levels of iRhom1 were slightly increased in the absence of ADAM17 in mEFs, indicating that its stability does not depend on ADAM17. These findings support a model in which iRhom2 and ADAM17 are obligate binding partners and indicate that iRhom2 stability requires the presence of ADAM17, whereas iRhom1 is stable in the absence of ADAM17

Impurity temperatures measured via line shape analysis in the island scrape-off-layer of Wendelstein 7-X

Impurity temperatures have been determined by a spectroscopic line shape analysis for several species in the divertor scrape-off-layer of the stellarator Wendelstein 7-X (W7-X). Examples include spectral lines from intrinsic elements (C II and C III, He I) as well as from seeded impurities (Ar II, N II) through the divertor gas inlet system. Both Doppler broadening and Zeeman splitting are found to contribute significantly to the impurity line shapes. Zeeman splitting arises due to the confining magnetic field in W7-X and complicates the line shape appearance. By attributing Doppler widths to each of the various Zeeman components, however, we demonstrate that reliable ion temperature values can be derived provided that the presence of the magnetic field is properly accounted for. The spectrally highly resolved lines are analyzed by means of a multi-parameter, least-squares fit routine, which accounts for Doppler broadening, Zeeman splitting, as well as the instrumental broadening of the spectrometer used to measure the spectral line shapes. By spectral fitting of the Zeeman features, it is also found that the line shape analysis can yield values for the local magnetic field, which can be used to localize the impurity radiation approximately provided that the line emission is dominant in a small area intersected by the lines of sight of the spectrometer

Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal–fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified