Medicine and Health Sciences Commons^™

Oligodendrocyte Rasg12v Expressed In Its Endogenous Locus Disrupts Myelin Structure Through Increased Mapk, Nitric Oxide, And Notch Signaling, Haley E. Titus, Alejandro Lopez-Juarez, Sadiq H. Silbak, Tilat A. Rizvi, Madeleine Bogard, Nancy Ratner

Health & Biomedical Sciences Faculty Publications and Presentations

Costello syndrome (CS) is a gain of function Rasopathy caused by heterozygous activating mutations in the HRAS gene. Patients show brain dysfunction that can include abnormal brain white matter. Transgenic activation of HRas in the entire mouse oligodendrocyte lineage resulted in myelin defects and behavioral abnormalities, suggesting roles for disrupted myelin in CS brain dysfunction. Here we studied a mouse model in which the endogenous HRas gene is conditionally replaced by mutant HRasG12V in mature oligodendrocytes, to separate effects in mature myelinating cells from developmental events. Increased myelin thickness due to decompaction was detectable within one month of HRasG12V expression …

Generalized Linear Mixed Model Analysis Of Urban-Rural Differences In Social And Behavioral Factors For Colorectal Cancer Screening, Ke-Sheng Wang, Xuefeng Liu, Muyiwa Ategbole, Xin Xie, Ying Liu, Chun Xu, Changchun Xie, Zhanxin Sha

Health & Biomedical Sciences Faculty Publications and Presentations

Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening.

Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses …

Principal Component Regression Analysis Of Nutrition Factors And Physical Activities With Diabetes, Ke-Sheng Wang, Ying Lu, Xin Xie, Shaoqing Gong, Chun Xu, Zhanxin Sha

Health & Biomedical Sciences Faculty Publications and Presentations

The associations of nutrition factors and physical activities with adult diabetes are inconsistent; while most of these factors are inter correlated. The aims of this study are to overcome the disturbance of the multicollinearity of the risk factors and examine the associations of these factors with diabetes using the principal component analysis (PCA) and regression analysis with principal component scores (PCS). Totally, 659 adults with diabetes and 2827 non-diabetic were selected from the 2012 Health Information National Trends Survey (HINTS 4, Cycle 2). PCA was utilized to deal with multicollinearity of the risk factors. Weighted univariate and multiple logistic regression …

Oligodendrocyte Nf1 Controls Aberrant Notch Activation And Regulates Myelin Structure And Behavior, Alejandro Lopez-Juarez, Haley E. Titus, Sadiq H. Silbak, Joshua W. Pressler, Tilat A. Rizvi, Madeleine Bogard, Michael R. Bennett, Georgianne Ciraolo, Michael T. Williams, Charles V. Vorhees, Nancy Ratner

Health & Biomedical Sciences Faculty Publications and Presentations

The RASopathy neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic disorders. In NF1 patients, neurological issues may result from damaged myelin, and mice with a neurofibromin gene (Nf1) mutation show white matter (WM) defects including myelin decompaction. Using mouse genetics, we find that altered Nf1 gene-dose in mature oligodendrocytes results in progressive myelin defects and behavioral abnormalities mediated by aberrant Notch activation. Blocking Notch, upstream mitogen-activated protein kinase (MAPK), or nitric oxide signaling rescues myelin defects in hemizygous Nf1 mutants, and pharmacological gamma secretase inhibition rescues aberrant behavior with no effects in wild-type …

Genetic Association Analysis Of Polymorphisms In Psd3 Gene With Obesity, Type 2 Diabetes, And Hdl Cholesterol, Shaoqing Gong, Chun Xu, Liang Wang, Ying Liu, Daniel Owusu, Beth A. Bailey, Yujing Li, Kesheng Wang

Health & Biomedical Sciences Faculty Publications and Presentations

Highlights

• First study of PSD3 gene with obesity, type 2 diabetes and HDL cholesterol.

• Identified 23 SNPs associated with obesity with p < 0.05 in gene discovery.

• 20 SNPs were associated with obesity in meta-analysis of two samples.

• 6 SNPs associated with type 2 diabetes and 11 associated with HDL.

• Findings offer new insights into the pathogenesis of obesity and diabetes.

Abstract

Background

The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level.

Methods

Multiple …

Applications Of Next-Generation Sequencing In Cancer Research And Molecular Diagnosis, Kesheng Wang, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Next-generation sequencing (NGS) technologies including DNA sequencing and RNA sequencing provide “omics” approaches to reveal genomic, transcriptomic, and epigenomic landscapes of individual cancers. A variety of genomic aberrations can be screened simultaneously, such as common and rare variants, structural variations (e.g. insertions and deletions), copy-number variation, and fusion transcripts. NGS technologies together with bioinformatics analysis, which expand our knowledge, are increasingly used to simultaneously analyze multiple genes in a cost and time-effective manner and have been applied in analyzing clinical cancer samples and offering NGS-based molecular diagnosis. Therefore, NGS is increasingly valuable as a tool for diagnosis for a number …

The Impact Of Drug And Gene Interaction On The Antipsychotic Medication For Schizophrenia, Michelle Cho, Adriana Contreras, Ashley Garza, Samantha Olvera, David Castillo, Gabriel A. De Erausquin, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Objective: Schizophrenia, a neuropsychiatric disorder, is known to be neurodevelopmentally progressive. Due to the extensive interindividual variability found in the responses of patients, management of schizophrenia has proven to be challenging. This interindividual variability to treatment could be justified by the variation of the enzymes in charge of metabolizing medications, especially those associated with cytochrome P450. Since genetic factors influence the phenotypic responses to drugs, researchers are involved in identifying schizophrenic genetic factors, which could impact responses and severe effects for commonly known neuroleptic drugs known as pharmacogenetics. In order to predict drug response at the personal level, genetic variants …

Systematically Characterizing Dysfunctional Long Intergenic Noncoding Rnas In Multiple Brain Regions Of Major Psychosis, Ke-Sheng Wang, Ying Liu, Shaoqing Gong, Chun Xu, Xin Xie, Liang Wang, Xingguang Luo

Health & Biomedical Sciences Faculty Publications and Presentations

Alzheimer's disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and age at onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 single nucleotide …

Bayesian Cox Proportional Hazards Model In Survival Analysis Of Hace1 Gene With Age At Onset Of Alzheimer’S Disease, Ke-Sheng Wang, Ying Liu, Shaoqing Gong, Chun Xu, Xin Xie, Liang Wang, Xingguang Luo

Health & Biomedical Sciences Faculty Publications and Presentations

Alzheimer’s Disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and Age at Onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 Single Nucleotide …