Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

1961-2014年西安市秋淋气候特征分析

利用1961-2014年8-10月西安市7个气象站逐日降水资料,采用降水强度指数分析了西安市秋淋天气气候变化特征.结果表明,20世纪90年代是近50年来西安市秋季9~10月降水量最少的阶段.1961年以来西安市共有23 a出现秋淋多雨时段,20世纪60年代至80年代中期较多,1983年和1984年出现强秋淋;20世纪80年代中期至21世纪10年代初期,只有1992年出现了1次秋淋天气;2011年以来,秋淋呈明显上升、增强趋势.1961-2014年秋淋天气过程平均降水量呈上升趋势,偏多年份主要出现在20世纪80年代初中期和21世纪.厄尔尼诺使秋季9~10月降水量减少,与秋淋天气存在明显的负相关关系.近54年西安市秋淋没有发生显著的气候突变,存在4~6 a、10 a和24 a左右的长振荡周期.     

WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway

Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40 domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway. D. Gao and R. Wang contributed equally to this work.     

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus

We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.     

FIDIC条款下项目的技术管理

文章阐述了在FIDIC条件下项目技术管理的主要内容及措施,为其他项目技术管理提供参考。     

我国湿地保护立法研究

湿地被称为“地球之肾”，是地球三大生态系统之一，在促进生态文明建设、构建和谐社会中具有重要作用．然而，近年来我国湿地破坏严重，其原因主要是我国湿地保护法律制度的不健全．我国湿地保护立法缺少中央立法、湿地内涵与外延不明确等，应借鉴发达国家经验提出相关完善建议．     

汾河流域降水量及蒸发量的空间变异性分析研究

借助于地质统计学方法对汾河流域的多年平均降雨量和蒸发量的空间变异性进行了分析,揭示了多年平均降水量和蒸发量的空间变异特征,并应用Kriging方法进行空间插值.分析结果表明,汾河流域多年平均降水量和蒸发量在不同的分割距离范围内有不同的空间相关性,多年平均降水量具有比较明显的地带性,蒸发量分布变化地带性不强.     

程控交换机的日常维护与管理

文章通过铁通公司使用的程控交换机出现的常见故障,提出了如何维护和管理等一系列措施,以期帮助程控人员解决一些疑难问题。     

Removable ears of 1-extendable graphs

<正> Carvalho,Lucchesi and Murty proved that any 1-extendable graph G different from K_2and C_(2n)has at least Δ(G)edge-disjoint removable ears,and any brick G distinct from K_4 and■hasat least Δ(G)-2 removable edges,where Δ(G)denotes the maximum degree of G.In this paper,weimprove the lower bounds for numbers of removable ears and removable edges of 1-extendable graphs.It is proved that any 1-extendable graph G different from K_2 and C_(2n)has at least χ′(G)edge-disjointremovable ears,and any brick G distinct from K_4 and■has at least χ′(G)-2 removable edges,whereχ′(G)denotes the edge-chromatic number of G.