Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk

ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.     

A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains

All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222–230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus.     

Bag-of-words representation for biomedical time series classification

Automatic analysis of biomedical time series such as electroencephalogram (EEG) and electrocardiographic (ECG) signals has attracted great interest in the community of biomedical engineering due to its important applications in medicine. In this work, a simple yet effective bag-of-words representation that is originally developed for text document analysis is extended for biomedical time series representation. In particular, similar to the bag-of-words model used in text document domain, the proposed method treats a time series as a text document and extracts local segments from the time series as words. The biomedical time series is then represented as a histogram of codewords, each entry of which is the count of a codeword appeared in the time series. Although the temporal order of the local segments is ignored, the bag-of-words representation is able to capture high-level structural information because both local and global structural information are well utilized. The performance of the bag-of-words model is validated on three datasets extracted from real EEG and ECG signals. The experimental results demonstrate that the proposed method is not only insensitive to parameters of the bag-of-words model such as local segment length and codebook size, but also robust to noise.     

Formaldehyde induces toxic effects and regulates the expression of damage response genes in BM-MSCs

In this study, we assessed the toxic effects of formaldehyde （FA） on mouse bone marrow mesenchymai stem cells （BM- MSCs）. Cytotoxicity was measured by using MTT assay. DNA strand breakage was detected by standard alkaline comet assay and comet assay modified with proteinase K （PK）. DNA-protein crosslinks （DPCs） were detected by KCI-SDS precipitation assay. We found that FA at a con- centration from 75 to 200 μM inhibited cell survival and induced DPCs over 125 μM. The PK-modified comet assay showed that FA-induced DNA strand breakage was increased in a dose-dependent manner from 75 to 200 μM. On the other hand, standard alkaline comet assay showed that DNA strand breakage was decreased with FA concen- tration over 125 μM. We confirmed by using Pearson cor- relation that there was a negative linear correlation between DPCs and survival rate （r = -0.987, P 〈 0.01） and positive linear relationships between DPCs and （i） sister chromatid exchange and （ii） micronucleus （r = 0.995, P〈 0.01; r = 0.968, P〈 0.01）. DNA damage RTz profiler polymerase chain reaction array was used to investigate the changes in the expression of damage response genes. Xpa and Xpc of the nucleotide excision repair pathway and Brca2, Rad51, and Xrcc2 of the homologous recombination pathway were all up-regulated in both 75 and 125 μM FA. However, the same genes were down-regulated with 175 μM FA. The expressions of Chekl and Husl, which are involved in cell cycle regulation, were altered in the same manner with 75, 125, and 175 μM FA. These results indicated that Xpa, Xpc, Brca2, Rad51, Xrcc2, Chekl, and Husl were essential for the BM-MSCs to counteract the effects of FA.     

铁还原菌降解石油烃的研究进展

铁还原菌是指能够利用细胞外Fe(III)作为末端电子受体,通过氧化有机物将Fe(III)还原为Fe(II)微生物的总称。铁还原作用广泛存在于土壤、河流、海洋、地表含水层以及高温高压的地下深部油藏。在厌氧或兼性厌氧条件下,Fe(III)还原耦合有机物的降解,对铁、碳元素的生物地球化学循环具有重要意义。本文介绍了铁还原菌的多样性和铁还原作用机理,综述了铁还原菌在石油烃降解方面的研究进展。此外,还总结了铁还原菌在生物修复中的潜在作用,并对未来的研究方向进行了展望。     

The D Domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells

Background

As a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2) has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4) was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear.

Methods

The interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro. We also investigated the interaction of LRRC4 and ERK1/2 and the role of the D domain in ERK activation in glioma cells.

Results

Here, we showed that LRRC4 and ERK1/2 interact via the D domain and CD domain, respectively. Following EGF stimuli, the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and abrogates ERK1/2 activation and nuclear translocation. In glioblastoma cells, ectopic LRRC4 expression competitively inhibited the interaction of endogenous mitogen-activated protein kinase (MEK) and ERK1/2. Mutation of the D domain decreased the LRRC4-mediated inhibition of MAPK signaling and its anti-proliferation and anti-invasion roles.

Conclusions

Our results demonstrated that the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells. These findings identify a new mechanism underlying glioblastoma progression and suggest a novel therapeutic strategy by restoring the activity of LRRC4 to decrease MAPK cascade activation.

     

CPI-17-mediated contraction of vascular smooth muscle is essential for the development of hypertension in obese mice

Several factors have been implicated in obesity-related hypertension, but the genesis of the hypertension is largely unknown. In this study, we found a significantly upregulated expression of CPI-17(C-kinasepotentiated protein phosphatase 1 inhibitor of 17 kDa) and protein kinase C(PKC) isoforms in the vascular smooth muscles of high-fat diet(HFD)-fed obese mice. The obese wild-type mice showed a significant elevation of blood pressure and enhanced calcium-sensitized contraction of vascular smooth muscles. However, the obese CPI-17-deficient mice showed a normotensive blood pressure, and the calcium-sensitized contraction was consistently reduced. In addition, the mutant muscle displayed an abolished responsive force to a PKC activator and a 30%-50% reduction in both the initial peak force and sustained force in response to various G protein-coupled receptor(GPCR) agonists. Our observations showed that CPI-17-mediated calcium sensitization is mediated through a GPCR/PKC/CPI-17/MLCP/RLC signaling pathway. We therefore propose that the upregulation of CPI-17-mediated calcium-sensitized vasocontraction by obesity contributes to the development of obesity-related hypertension.     

水稻稻瘟病抗性基因的克隆、育种利用及稻瘟菌无毒基因研究进展

稻瘟病是世界上影响水稻(Oryza sativa)粮食生产的主要病害之一, 抗病基因的发掘与利用是抗病育种的基础和核心。随着寄主水稻和病原菌稻瘟病菌(Magnaporthe oryzae)基因组测序和基因注释的完成, 水稻和稻瘟病菌的互作体系成为研究植物与真菌互作的模式系统。该文对稻瘟病抗病基因的遗传、定位、克隆及育种利用进行概述, 并通过生物信息学分析方法, 探讨了水稻全基因组中NBS-LRR类抗病基因在水稻12条染色体上的分布情况, 同时对稻瘟病菌无毒基因的鉴定及无毒蛋白与抗病蛋白的互作进行初步分析。最后对稻瘟病抗病基因研究存在的问题进行分析并展望了未来的研究方向, 以期为水稻抗稻瘟病育种发展和抗病机制的深入理解提供参考。