Split Ga vacancies and the unusually strong anisotropy of positron annihilation spectra in beta-Ga2O3

We report a systematic first-principles study on positron annihilation parameters in the beta-Ga2O3 lattice and Ga monovacancy defects complemented with orientation-dependent experiments of the Doppler broadening of the positron-electron annihilation. We find that both the beta-Ga2O3 lattice and the considered defects exhibit unusually strong anisotropy in their Doppler broadening signals. This anisotropy is associated with low symmetry of the beta-Ga2O3 crystal structure that leads to unusual kind of one-dimensional confinement of positrons even in the delocalized state in the lattice. In particular, the split Ga vacancies recently observed by scanning transmission electron microscopy produce unusually anisotropic positron annihilation signals. We show that in experiments, the positron annihilation signals in beta-Ga2O3 samples seem to be often dominated by split Ga vacancies.Peer reviewe

Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA

Contains fulltext : 253059.pdf (Publisher’s version ) (Open Access

Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice

Human osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OA spontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. We exploit the lack of overt OA in female STR/Ort and in both sexes of parental, control CBA mice to explore whether early divergence in tibial bone mass or shape are linked to emergent OA

Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall1. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFb pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity3. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes4,5. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFb signaling represent a new treatment strategy

New fishes from the Belgian Congo

6 p. : ill. ; 24 cm.Includes 1 bibliographical reference (p. 6)

Necrostatin-1 Analogues: Critical Issues on the Specificity, Activity and In Vivo Use in Experimental Disease Models

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × less effective than Nec-1 in inhibiting human RIPK1 kinase activity in vitro, it was only 10 times less potent than Nec-1 and Nec-1s in a mouse necroptosis assay and became even equipotent at high concentrations. Along the same line, in vivo, high doses of Nec-1, Nec-1i and Nec-1s prevented tumor necrosis factor (TNF)-induced mortality equally well, excluding the use of Nec-1i as an inactive control. Paradoxically, low doses of Nec-1 or Nec-1i, but not Nec -1s, even sensitized mice to TNF-induced mortality. Importantly, Nec-1s did not exhibit this low dose toxicity, stressing again the preferred use of Nec-1s in vivo. Our findings have important implications for the interpretation of Nec-1-based data in experimental disease models

A novel strategy for the comprehensive analysis of the biomolecular composition of isolated plasma membranes

A methodology for rapid, high-purity isolation of plasma membranes using superparamagnetic nanoparticles is described. The method is illustrated with high-resolution proteomic, glycomic and lipidomic analyses of presenilin-deficient cells