Disease-driven detection of differential inherited SNP modules from SNP network

Detection of the synergetic effects between variants, such as single-nucleotide polymorphisms (SNPs), is crucial for understanding the genetic characters of complex diseases. Here, we proposed a two-step approach to detect differentially inherited SNP modules (synergetic SNP units) from a SNP network. First, SNP-SNP interactions are identified based on prior biological knowledge, such as their adjacency on the chromosome or degree of relatedness between the functional relationships of their genes. These interactions form SNP networks. Second, disease-risk SNP modules (or sub-networks) are prioritised by their differentially inherited properties in IBD (Identity by Descent) profiles of affected and unaffected sibpairs. The search process is driven by the disease information and follows the structure of a SNP network. Simulation studies have indicated that this approach achieves high accuracy and a low false-positive rate in the identification of known disease-susceptible SNPs. Applying this method to an alcoholism dataset, we found that flexible patterns of susceptible SNP combinations do play a role in complex diseases, and some known genes were detected through these risk SNP modules. One example is GRM7, a known alcoholism gene successfully detected by a SNP module comprised of two SNPs, but neither of the two SNPs was significantly associated with the disease in single-locus analysis. These identified genes are also enriched in some pathways associated with alcoholism, including the calcium signalling pathway, axon guidance and neuroactive ligand-receptor interaction. The integration of network biology and genetic analysis provides putative functional bridges between genetic variants and candidate genes or pathways, thereby providing new insight into the aetiology of complex diseases.     

EGF receptor clustering is induced by a 0.4 mT power frequency magnetic field and blocked by the EGF receptor tyrosine kinase inhibitor PD153035

Atomic force microscopy (AFM), transmission electron microscopy (TEM), and confocal laser scanning microscopy were used to investigate the effects of a 50 Hz 0.4 mT magnetic field (MF) on the clustering of purified epidermal growth factor receptors (EGFRs) and EGFRs in Chinese hamster lung (CHL) cell membrane. The results demonstrate that exposing purified EGFRs to the MF for 30 min induces receptor clustering. The peak height of apparent clusters increased from 1.42 +/- 0.18 (sham-exposed) to 3.08 +/- 0.38 nm (exposed) while the mean half-width increased from 21.7 +/- 2.2 to 33.0 +/- 4.0 nm. A similar effect was also observed by TEM. Treatment of purified EGFR with PD153035 (PD), an EGFR-specific tyrosine kinase (TK) inhibitor, inhibited the MF-induced EGFR clustering of the purified proteins, an effect also observed for the receptors in cell membrane in the absence of EGF. These results strongly suggest that the 50 Hz 0.4 mT MF interferes with the EGFR signaling pathway, most likely by interacting with the cytoplasmic TK domain.     

Identification and characterization of FHL3 as a novel angiogenin-binding partner

Angiogenin (Ang) is known to induce cell proliferation and inhibit apoptosis by cellular signaling pathways and by direct nuclear functions of Ang, but the mechanism of action for Ang is not yet clear. The aim of present study was to identify novel binding partner of Ang and to explore the underlying mechanism. With the use of yeast two-hybrid screening system, Ang was used as the bait to screen human fetal hepatic cDNA library for interacting proteins. Four and a half LIM domains 3 (FHL3) was identified as a novel Ang binding partner. The interaction between Ang and the full length FHL3 was further confirmed by yeast two-hybrid assay, co-immunoprecipitation and GST pull-down assays. Furthermore, FHL3 was required for Ang-mediated HeLa cell proliferation and nuclear translocation of Ang. These findings suggest that the interaction between Ang and FHL3 may provide some clues to the mechanisms of Ang-regulated cell growth and apoptosis.     

Five New Guaiane Sesquiterpenes from the Endophytic Fungus Xylaria sp. YM 311647 of Azadirachta indica

Five new guaiane sesquiterpenes, 1 – 5 , were isolated from the culture broth of the endophytic fungus Xylaria sp. YM 311647, isolated from Azadirachta indica A. Juss . The structures of these compounds were elucidated on the basis of spectroscopic analyses, and their inhibitory activities against five pathogenic fungi were evaluated. All guaiane sesquiterpenes showed moderate or weak antifungal activities in a broth microdilution assay.     

Characterization of culturable bacterial endophytes of switchgrass (Panicum virgatum L.) and their capacity to influence plant growth

Switchgrass (Panicum virgatum L.) is a perennial warm season grass that is native to the plains of North America and is widely grown as a forage, bioenergy or groundcover crop. Despite its importance, a bottleneck in switchgrass production is poor seedling vigor, which as a perennial crop represents an important time for management. Herein, data identify a suite of culturable bacterial microflora extracted from switchgrass, and show their capability to influence host plant growth and development. A total of 307 bacterial isolates were cultured and isolated from surface sterilized switchgrass biomass and sequence identified into 76 strains (subspecies classification), 36 species and 5 phyla. Approximately 58% of bacterial strains, when reintroduced into surface‐sterilized switchgrass seeds, were documented to increase lamina length (cm from base to tip after 60 days growth) relative to uninoculated controls. Ecologically, Phylum Firmicutes was the most abundant bacterial classification and encompassed 75% of all isolates. Although the culturable bacterial community studies herein represent an unknown and assumedly minor proportion of the total microbiome, by focusing on culturable bacteria, we delineate functional feedback between the presence of isolated bacteria and switchgrass seedling growth.     

Enhanced production of Penicillium expansum PED-03 lipase through control of culture conditions and application of the crude enzyme in kinetic resolution of racemic Allethrolone

Alkaline lipase production was performed in submerged fermentation by Penicillium expansum PED-03. It was found that the suitable carbon source and nitrogen source for lipase production were 0.5% starch and 4.0% soybean meal, respectively. The maximal lipase activity (850 U/mL) of production was achieved at initial pH 5.5-6.0, 26 degrees C, 72 h. Tween-80 was an effective enhancer for lipase production. Agitation speed of the fermentor played an important role, and the suitable agitation speed for lipase production was 500 r/min. The lipase was stable within the range of pH 7.0-10.0 and 20-40 degrees C, and the optimum conditions for the enzymatic reaction were 35 degrees C and pH 9.5. The enzymatic resolution of racemic allethrolone (4-hydroxy-3-methyl-2-(2-propenyl)-2- cyclopenten-1-one) was carried out by the lipase from P. expansum PED-03, and the conversion reached 48% with excellent enantioselectivity (E > 100), which showed a good application potential in the production of optically pure allethrolone.     

利用激光扫描共聚焦显微镜研究视皮层脑片长时程增强过程中核酸的变化

本文使用 1 5— 2 0天龄幼年大鼠视皮层脑片的标本 ,在通氧状态下 ,用荧光探针 AO染色 ,激光扫描共聚焦显微镜对全脑片不同层面进行共聚焦断层扫描 ,沿纵轴每 2 0μm扫一次 ,共扫描 1 6次。再利用总值方式的投影算法对其三维重建 ,分析幼年大鼠视皮层脑片长时程增强过程中核酸的变化。     

纽氏钝绥螨、尼氏钝绥螨及其猎物—桔全爪螨生态学特性的比较研究

本文从天敌与猎物的种群内禀增长力,天敌对猎物不同密度的功能反应及数值反应三个方面来评价和比较纽氏钝绥螨、尼氏钝绥螨时其猎物——枯全爪螨的控制作用。在五种温度下,两种捕食螨的种群内禀增长力都大于桔全爪螨。它们对猎物的功能反应属HollingⅡ型。尼氏钝绥螨的捕食量大于纽氏钝绥螨,在25℃时两种捕食螨捕食量最大,应用Rogers的模型能较好地对试验结果进行模拟。尼氏钝绥螨对桔全爪不同虫态的取食不存在选择效应,纽氏钝绥螨则嗜食若螨和幼螨。两种捕食螨对桔全爪螨的数值反应表明,仅供给桔全爪螨雌成螨作为食物,对两种捕食螨都不利,尤其对尼氏钝绥螨更为明显。综上所述,两种捕食螨能比较有效地控制桔全爪螨种群,当猎物密度较高时,尼氏钝绥螨控制效果优于纽氏钝绥螨,但纽氏钝绥螨控制效果优于纽氏钝绥螨,但纽氏钝绥螨田间种群数量比尼氏钝绥螨稳定。柑桔园中存在其它补充食物时对这两种捕食敌有利。     

9号染色体臂间倒位21例分析

在2 703例遗传咨询门诊病例中检出9号染色体臂间倒位21例,将本组inv(9)的频率与普通群体inv(9)的频率作比较,并通过对伴有其它性状的inv(9)家系的分析,讨论了inv(9)的遗传效应问题。 Abstract:　Twenty one cases of pericentric inversion of chromosome 9 were found in 2703 patients asking genetic counseling. The percentage of inv(9) in this group was compared with that in normal population. Two special pedigrees with inv(9) were analyzed and the genetic effects of inv(9) were discussed.