A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition

Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies.     

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers

Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection.     

Common variation at 10p12.31 near MLLT10 influences meningioma risk

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.     

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

西北地区人口-经济-水环境质量耦合协调发展研究

基于2005～2014年西北五省人口-经济-水环境质量相关数据,构建耦合协调评价指标体系。运用统计学和GIS方法对近10年来西北地区人口-经济-水耦合协调发展的时空演变进行分析,发现2005～2014年,耦合类别变化情况为勉强耦合-初级耦合-中级耦合,耦合协调度持续上升表明三个子系统之间的协调促进作用增强,系统逐步由无序走向有序;近10年来,西北五省耦合协调度均有不同程度提升,其中青海省提升幅度最大,达到了0.44,陕西省提升幅度为0.044,是五省中提升幅度最小的省区;不论是区域整体还是区域内部各个省份,经济和人口对系统的推动作用均逐步增强,而水环境质量则逐步失去对各区域发展的推动力,表明区域发展的动力逐步由资源转向经济和人口,发展的可持续性增强。     

星系的生命和呼吸

<正>科学家追踪气体随时间和空间的变化,探寻恒星群出生及死亡的方式。天文学家对宇宙的大部分了解来自他们能够看到的东西,因此,他们的理论总是偏爱明亮的恒星和星系。然而,宇宙中的大部分常规物质都是以昏暗的气体形式存在的。称作星系际介质的气体充满星系间的空间;而环星系介质的气体则环绕在星系附近。这两个区域的气体管控星系诞生、成长和死亡,也详细记录了整个宇宙的     

基于EXCEL和MATLAB的矩形薄片热传导计算与仿真研究

对二维导热问题进行了离散化研究,推导出了节点差分方程,以矩形薄片为例,用MS.Excel对节点温度进行了计算,用MATLAB对计算结果进行了仿真,得到了薄片的温度分布仿真图.