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Single cell molecular alterations reveal target cells and pathways of concussive brain injury

The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the...

MicroRNA-21 and PDCD4 expression during in vitro oocyte maturation in pigs

Background MicroRNA (miRNA) are small non-coding RNA molecules critical for regulating cellular function, and are abundant in the maturing oocyte and developing embryo. MiRNA-21 (MIR21) has been shown to elicit posttranscriptional gene regulation in several tissues associated with rapid cell proliferation in addition to demonstrating anti-apoptotic features through interactions...

Nutritional systems biology of type 2 diabetes

only rapid discovery but also timely translation into humans. Acknowledgments Xia Yang is funded by the American Heart Association Scientist Development Grant and the National Institute of Diabetes and

Novel microRNA families expanded in the human genome

Zhi-Qiang Du 0 Cai-Xia Yang 0 Max F Rothschild Jason W Ross 0 Equal contributors Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University , 2255 Kildee Hall, Ames

A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits

Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and...

High Metastaticgastric and Breast Cancer Cells Consume Oleic Acid in an AMPK Dependent Manner

Gastric cancer and breast cancer have a clear tendency toward metastasis and invasion to the microenvironment predominantly composed of adipocytes. Oleic acid is an abundant monounsaturated fatty acid that releases from adipocytes and impinges on different energy metabolism responses. The effect and underlying mechanisms of oleic acid on highly metastatic cancer cells are not...

Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci

To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of...

Genetic and Dietary Determinants of Insulin-Like Growth Factor (IGF)-1 and IGF Binding Protein (BP)-3 Levels among Chinese Women

Background Higher insulin-like growth factor (IGF)-1 and lower IGF binding protein (BP)-3 levels have been associated with higher commoncancer risk, including breast cancer. Dietary factors, genetic polymorphisms, and the combination of both may influence circulating IGF-1 and IGFBP-3 serum concentrations. Methods From September 2011 to July 2012, we collected demographic...

HIV-, HCV-, and Co-Infections and Associated Risk Factors among Drug Users in Southwestern China: A Township-Level Ecological Study Incorporating Spatial Regression

Background The human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are major public health problems. Many studies have been performed to investigate the association between demographic and behavioral factors and HIV or HCV infection. However, some of the results of these studies have been in conflict. Methodology/Principal Findings The data of all entrants in the 11...

Integrating Genetic Association, Genetics of Gene Expression, and Single Nucleotide Polymorphism Set Analysis to Identify Susceptibility Loci for Type 2 Diabetes Mellitus

Laboratories, Boston, Massachusetts (Danielle M. Greenawalt); Sage Bionetworks, Seattle, Washington (Solveig K. Sieberts, Hua Zhong, Xia Yang, Justin Guinney); Department of Epidemiology, Harvard School of

S100A8 and S100A9 Are Associated with Colorectal Carcinoma Progression and Contribute to Colorectal Carcinoma Cell Survival and Migration via Wnt/β-Catenin Pathway

Background and Objective S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor...

Dual Inhibition of Plasminogen Kringle 5 on Angiogenesis and Chemotaxis Suppresses Tumor Metastasis by Targeting HIF-1α Pathway

Yang Zhong-Han Yang Jian-Xing Ma Chun-Kui Shao Guo-Quan Gao Anjali Jain, Cedars-Sinai Medical Center, United States of America We had demonstrated that plasminogen kringle 5 (K5), a potent angiogenic

Recombinant Vascular Endothelial Growth Factor 121 Attenuates Autoantibody-Induced Features of Pre-eclampsia in Pregnant Mice

Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the...

Integrative Analysis of a Cross-Loci Regulation Network Identifies App as a Gene Regulating Insulin Secretion from Pancreatic Islets

Complex diseases result from molecular changes induced by multiple genetic factors and the environment. To derive a systems view of how genetic loci interact in the context of tissue-specific molecular networks, we constructed an F2 intercross comprised of >500 mice from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mouse strains made genetically obese by the Leptinob...

Integrative Genomics Reveals Novel Molecular Pathways and Gene Networks for Coronary Artery Disease

Nilesh J. Samani Heribert Schunkert Thomas Quertermous Ruth McPherson Xia Yang Themistocles L. Assimes The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may...

Diurnal variation of the human adipose transcriptome and the link to metabolic disease

Background Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. Methods The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy...

Dosage compensation is less effective in birds than in mammals

BackgroundIn animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X-linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in...

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene...