0000000000471098
AUTHOR
Xu Wang
Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error
Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG…
OTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.
Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell‐intrinsic mechanism governing astrocyte function during MS and EAE. Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE. Mice with astrocyte‐specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1‐deficient astrocytes were hy…
Genome-wide associations for birth weight and correlations with adult disease
Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genet…
A Planar Generator for a Wave Energy Converter
This article presents a permanent magnet planar translational generator which is able to exploit multiple modes of sea wave energy extraction. Linear electrical generators have recently been studied for the exploitation of sea wave energy, but, to the best of our knowledge, no synchronous planar translational generator has been proposed. In this article, to maximize the energy extraction, we have considered all the potential modes of motion due to wave excitation and included them within the mathematical model of the proposed system. The principle of operation of the generator can be summarized as follows: the moving part (translator) of the generator is driven from the sea waves and induce…
Energy spectrum of cosmic protons and helium nuclei by a hybrid measurement at 4300 m a.s.l.
The energy spectrum of cosmic Hydrogen and Helium nuclei has been measured, below the so-called "knee", by using a hybrid experiment with a wide field-of-view Cherenkov telescope and the Resistive Plate Chamber (RPC) array of the ARGO-YBJ experiment at 4300 m above sea level. The Hydrogen and Helium nuclei have been well separated from other cosmic ray components by using a multi-parameter technique. A highly uniform energy resolution of about 25% is achieved throughout the whole energy range (100 TeV - 700 TeV). The observed energy spectrum is compatible with a single power law with index gamma=-2.63+/-0.06.
A20 expression in dendritic cells protects mice from LPS-induced mortality
DCs contribute to immune homeostasis under physiological conditions and regulate the immune activation during infection. The deubiquitinase A20 inhibits the activation of NF-κB-dependent immune reactions, and prevents the hyperactivation of DCs under steady-state conditions. However, the role of DC-specific A20 under pathological conditions is unknown. Here, we demonstrate that upon injection of low-dose LPS, mice with DC-specific A20 deletion (CD11c-Cre A20(fl/fl) ) died within 6 h, whereas A20(fl/fl) controls survived. LPS-induced mortality in CD11c-Cre A20(fl/fl) mice was characterized by increased serum levels of IL-2, IL-10, IL-12, IFN-γ, and TNF. Upon LPS stimulation, the activation o…
Women executives and financing pecking order of GEM-listed companies: Moderating roles of social capital and regional institutional environment
Abstract This paper investigates the financing options of female executives within China’s unique environment. We examined 154 GEM enterprises listed on the Shenzhen Stock Exchange from 2009 to 2016. The data were analyzed using statistical procedures including multilevel regression analysis based on the existing financing pecking order models. Empirical evidence shows that women executives are less likely to use internal and debt financing. In terms of internal financing willingness, social capital and external institutional environment have negative and positive moderating effects respectively. In terms of debt financing willingness, social capital has a positive moderating effect. In add…
Protective dendritic cell responses against listeriosis induced by the short form of the deubiquitinating enzyme CYLD are inhibited by full-length CYLD
The deubiquitinating enzyme CYLD is an important tumor suppressor and inhibitor of immune responses. In contrast to full-length CYLD, the immunological function of the naturally occurring short splice variant of CYLD (sCYLD) is insufficiently described. Previously, we showed that DCs, which lack full-length CYLD but express sCYLD, exhibit augmented NF-κB and DC activation. To explore the function of sCYLD in infection, we investigated whether DC-specific sCYLD regulates the pathogenesis of listeriosis. Upon Listeria monocytogenes infection of CD11c-Cre Cyld(ex7/8 fl/fl) mice, infection of CD8α(+) DCs, which are crucial for the establishment of listeriosis in the spleen, was not affected. Ho…