Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.     

GC/MS法追踪摇头丸杂质体系

本文运用GS/MS的总离子流法,选择离子法,对南京地区常见的几种摇头丸进行全面分析,找出与合成途径相关的痕量杂质,根据杂质情况初步确定其合成途径.     

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.     

鲁克沁构造带稠油成藏机制研究

吐哈盆地台南凹陷鲁克沁构造带中的北西走向断层受挤压强烈 ,封闭性好 ;而北东走向断层封闭性差 ,常成为油气运移的良好通道。由于本区断块圈闭的有效性差 ,故不具备大规模聚集稀油的条件 ,但对稠变到一定程度的稠油能起较好的封堵作用。鲁克沁构造带高粘重质油的形成是原油运移和成藏阶段双重稠变作用的结果 ,并且油气的聚集是一个动态的过程。随着原油的逐渐稠变 ,所需要的封堵条件逐渐降低 ,油气的聚集过程才趋于稳定。鲁克沁构造带构造后期变革主要表现在构造幅度的增大 ,而未发生强烈的断裂作用 ,因此 ,前侏罗系油藏得以完好地保存     

求取剩余油饱和度的一种实用方法

分析了水驱油田地质、测井及开发动态特征，提出了用生产井含水率资料结合测井资料求取产层平均剩余油饱和度的方法。阐述了该方法的基本模型和计算过程，并以实例计算说明了这种方法的实际应用效果。结果表明，该方法操作简便、实用性强、计算结果可靠，且能准确反映储层的剩余油分布特征。这种方法也避免了水淹层混合液电阻率、岩电系数和水淹层电阻率求取值失真的影响。     

Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis

We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.     

Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration.     

渤海湾盆地早第三纪构造样式与油气藏的关系

渤海湾盆地早第三纪构造样式可归结为５种基本类型和３个演化序列。研究结果表明,构造样式及其演化控制着烃源岩的发育,决定着油气藏的类型和展布,制约着含油气系统的范围。综合考虑含油气系统的各个要素,在渤海湾盆地可划分出６个大的含油气系统,分别位于各个坳陷中,并受坳陷的限制。进一步考虑坳陷内凸起构造单元的分割作用,可划分出１３个小的含油气系统。