cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue

Genome-wide association studies (GWAS) have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL) analyses to investigate possible regulatory functions on the expression of neighboring genes. Forty microsatellite stable and CpG island methylator phenotype-negative colorectal tumors and paired adjacent normal colon tissues were used for genome-wide SNP and gene expression profiling. We found that three risk variants (rs10795668, rs4444235 and rs9929218, using near perfect proxies rs706771, rs11623717 and rs2059252, respectively) were significantly associated (FDR q-value ≤0.05) with expression levels of nearby genes (<2 Mb up- or down-stream). We observed an association between the low colorectal cancer risk allele (A) for rs10795668 at 10p14 and increased expression of ATP5C1 (q = 0.024) and between the colorectal cancer high risk allele (C) for rs4444235 at 14q22.2 and increased expression of DLGAP5 (q = 0.041), both in tumor samples. The colorectal cancer low risk allele (A) for rs9929218 at 16q22.1 was associated with a significant decrease in expression of both NOL3 (q = 0.017) and DDX28 (q = 0.046) in the adjacent normal colon tissue samples. Of the four genes, DLGAP5 and NOL3 have been previously reported to play a role in colon carcinogenesis and ATP5C1 and DDX28 are mitochondrial proteins involved in cellular metabolism and division, respectively. The combination of GWAS findings, prior functional studies, and the cis-eQTL analyses described here suggest putative functional activities for three of the colorectal cancer GWAS identified risk loci as regulating the expression of neighboring genes.     

Meta-analysis of new genome-wide association studies of colorectal cancer risk

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8?×?10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p?相似文献   

青藏高原沙柳河流域自然径流驱动的流域生物信息流量化特征——以环境微生物为指标

物质流、能量流、信息流是生态系统过程研究中的三大主题。然而，在流域生态学研究中，有关信息流的研究一直缺位。为了推动流域信息流研究，从生物信息流切入，提出"流域生物信息流"概念，将其定义为"生物信息依托于流域生态系统过程在不同空间和系统之间进行传递、交流、作用、反馈的路径、过程与控制"，并将其研究内容拟定为主要关注于水陆间、干支流间、上下游间、不同生态斑块间的流域生物信息流及其周期性节律和趋势性变迁，以及地貌、水文、人类活动等对这些生物信息流的影响等。然后，以青藏高原上青海湖重要入湖河流--沙柳河的河流水体微生物和岸带土壤微生物为研究对象，利用环境DNA技术，对沙柳河流域的自然径流驱动的流域生物信息流进行量化研究。结果表明（1）岸带土壤到水体的流域生物信息流主要由地表表面流、地下潜流等驱动，并受环境过滤效应影响，其输移效率降雨天约为62.76%、晴天约为44.16%，其中输移能力降雨天约为68.49%、晴天约为56.82%，环境过滤效应降雨天约为8.38%、晴天约为22.28%；（2）水体上游到下游的流域生物信息流主要由河川径流驱动，并受衰减效应影响，其基础综合输移效率约为97.41%/km，其中径流输移能力约为99.42%/km，无效流域生物信息流占比约为43.46%，无效流域生物信息流的半衰距离约为14.52 km；（3）降雨通过增加地表表面流等的冲蚀搬运能力并削弱环境过滤效应，促使岸带土壤到水体的流域生物信息流输移能力和输移效率增大；（4）流域生物信息流的输入在一定程度上增加了输入地的可检出生物多样性，但这种增加对于流水生态系统来讲是非累积的。     

Plant performance responds to intraspecific variation in soil inocula from individual Solidago clones

Plant Ecology - Plant–soil microbe interactions are a key determinant of plant community composition and structure, with each plant species generating a unique soil microbiota. However, the...     

Inhibition of microbial concrete corrosion by Acidithiobacillus thiooxidans with functionalised zeolite-A coating

The inhibition of the corrosive action of Acidithiobacillus thiooxidans on concrete specimens coated by functionalised zeolite-A containing 14% zinc and 5% silver by weight was studied. Uncoated concrete specimens, epoxy-coated concrete specimens (EP), and functionalised zeolite-A coated concrete specimens with epoxy to zeolite weight ratios of 3:1 (Z1), 2:2 (Z2) and 1:3 (Z3) were studied. Specimens were characterised by x-ray powder diffraction and field emission scanning electron microscopy for the identification of corrosion products and morphological changes. Biomass growth at the conclusion of the 32-day experiments was 4, 179 and 193 mg volatile suspended solids g(-1) sulphur for the uncoated, EP and Z1 specimens, whereas that of Z2 and Z3 were negligible. In the uncoated, EP and Z1 specimens, sulphate production rates were 0.83, 9.1 and 8.8 mM SO(4)(2-) day(-1) and the specific growth rates, mu, were 0.14, 0.57 and 0.47 day(-1), respectively. The corresponding values for Z2 and Z3 were negligible due to their bacterial inhibition characteristics.     

2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)

This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.     

Rapid diagnosis of tuberculosis by detection of mycobacterial lipoarabinomannan in urine

There is an urgent need for improved tools for laboratory diagnosis of active tuberculosis (TB). Here, we describe two methods, a catch-up ELISA and a dipstick test based on the detection in urine of lipoarabinomannan (LAM). LAM is a major and specific glycolipid component of the outer mycobacterial cell wall. Preliminary experiments showed that LAM is excreted in the urine of mice injected intraperitoneally with a crude cell wall preparation of Mycobacterium tuberculosis. Both methods were highly sensitive, detecting LAM at concentrations of 1 ng/ml and 5 pg/ml, respectively. Of 15 patients with active TB, all showed intermediate to high levels of LAM in their urine (absorbance values from 0.3 to 1.2, mean 0.74). Only one sample showed an absorbance value below the chosen cut off value of 0.4. All but one of the urine samples from 26 healthy nursing workers exhibited OD value below 0.4 cut off. These methods may prove valuable for rapid and simple diagnosis of TB in particular in developing countries lacking biosafety level 3 (BSL3) facilities.