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991.
992.
Understanding the root molecular and genetic causes driving complex traits is a fundamental challenge in genomics and genetics. Numerous studies have used variation in gene expression to understand complex traits, but the underlying genomic variation that contributes to these expression changes is not well understood. In this study, we developed a framework to integrate gene expression and genotype data to identify biological differences between samples from opposing complex trait classes that are driven by expression changes and genotypic variation. This framework utilizes pathway analysis and multi-task learning to build a predictive model and discover pathways relevant to the complex trait of interest. We simulated expression and genotype data to test the predictive ability of our framework and to measure how well it uncovered pathways with genes both differentially expressed and genetically associated with a complex trait. We found that the predictive performance of the multi-task model was comparable to other similar methods. Also, methods like multi-task learning that considered enrichment analysis scores from both data sets found pathways with both genetic and expression differences related to the phenotype. We used our framework to analyze differences between estrogen receptor (ER) positive and negative breast cancer samples. An analysis of the top 15 gene sets from the multi-task model showed they were all related to estrogen, steroids, cell signaling, or the cell cycle. Although our study suggests that multi-task learning does not enhance predictive accuracy, the models generated by our framework do provide valuable biological pathway knowledge for complex traits. 相似文献
993.
994.
Background
In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors.Objective
To obtain more precise and accurate cerebral fMRI mapping of acupuncture.Design and Setting
A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China.Participants
Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D.Interventions
Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI.Results
Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas.Conclusions
The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results. 相似文献995.
Kemperly Dynon Sophea Heng Michelle Puryer Ying Li Kelly Walton Yaeta Endo Guiying Nie 《PloS one》2012,7(9)
Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13–14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum. 相似文献
996.
Two goose-type lysozymes (designated as MGgLYZ1 and MGgLYZ2) were identified from the mussel Mytilus galloprovincialis. MGgLYZ1 mRNA was widely expressed in the examined tissues and responded sensitively to bacterial challenge in hemocytes, while MGgLYZ2 mRNA was predominately expressed and performed its functions in hepatopancreas. However, immunolocalization analysis showed that both these lysozymes were expressed in all examined tissues with the exception of adductor muscle. Recombinant MGgLYZ1 and MGgLYZ2 could inhibit the growth of several Gram-positive and Gram-negative bacteria, and they both showed the highest activity against Pseudomonas putida with the minimum inhibitory concentration (MIC) of 0.95–1.91 µM and 1.20–2.40 µM, respectively. Protein sequences analysis revealed that MGgLYZ2 had lower isoelectric point and less protease cutting sites than MGgLYZ1. Recombinant MGgLYZ2 exhibited relative high activity at acidic pH of 4–5, while MGgLYZ1 have an optimum pH of 6. These results indicated MGgLYZ2 adapted to acidic environment and perhaps play an important role in digestion. Genomic structure analysis suggested that both MGgLYZ1 and MGgLYZ2 genes are composed of six exons with same length and five introns, indicating these genes were conserved and might originate from gene duplication during the evolution. Selection pressure analysis showed that MGgLYZ1 was under nearly neutral selection while MGgLYZ2 evolved under positive selection pressure with three positively selected amino acid residues (Y102, L200 and S202) detected in the mature peptide. All these findings suggested MGgLYZ2 perhaps served as a digestive lysozyme under positive selection pressure during the evolution while MGgLYZ1 was mainly involved in innate immune responses. 相似文献
997.
Qing Xia Zi-Xian Chen Yi-Chao Wang Yu-Shui Ma Feng Zhang Wu Che Da Fu Xiao-Feng Wang 《PloS one》2012,7(11)
Background
Melatonin receptor 1B (MTNR1B) belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction.Methods
PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested.Results
A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153) on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02–1.08; P<10−4) and 1.04 (95% CI: 0.98–1.10; P = 0.20) were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility.Conclusions
This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D. 相似文献998.
999.
1000.
Cui Z Wang J Zhu C Huang X Lu J Wang Q Chen Z Wang J Zhang Y Gu D Jing L Chen J Zheng R Qin L Yang H Jin R Liu Z Bi A Liu J Hu Z 《PloS one》2012,7(4):e36331