Medicine and Health Sciences Commons^™

Sequence Data And Association Statistics From 12,940 Type 2 Diabetes Cases And Controls, Jason Flannick, Christian Fuchsberger, Anubha Mahajan, Tanya M. Teslovich, Vineeta Agarwala, Kyle J. Gaulton, Lizz Caulkins, Rector Arya, Ravi Duggirala, Joanne E. Curran, Satish Kumar, John Blangero

School of Medicine Publications and Presentations

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1–5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency …

Impact Of The G84e Variant On Hoxb13 Gene And Protein Expression In Formalin-Fixed, Paraffin-Embedded Prostate Tumours, Liesel M. Fitzgerald, Kelsie Raspin, James R. Marthick, Matt A. Field, Roslyn C. Malley, Russell J. Thomson, Nicholas B. Blackburn, Erika Banks, Annette Banks, Jac C. Charlesworth, Shaun Donovan, Joanne L. Dickinson

School of Medicine Publications and Presentations

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type …

Exome Sequences Of Multiplex, Multigenerational Families Reveal Schizophrenia Risk Loci With Potential Implications For Neurocognitive Performance, Mark Kos, Melanie A. Carless, Juan M. Peralta, Joanne E. Curran, Ellen E. Quillen, Marcio Almeida, August N. Blackburn, Lucy Blondell, David Roalf, Michael F. Pogue-Geile, Harald H. H. Goring, Laura Almasy

School of Medicine Publications and Presentations

Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based …

Gastrin Induces Nuclear Export And Proteasomal Degradation Of Menin In Enteric Glial Cells, Sinju Sundaresan, Cameron A. Meininger, Anthony J. Kang, Amanda L. Photenhauer, Michael M. Hayes, Nirakar Sahoo, Jolanda Lindenberg, Jolanta Grembecka, Tomasz Cierpicki, Lin Ding

Biology Faculty Publications and Presentations

Background & aims: The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner's glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia.

Methods: Primary enteric glial cultures were generated from the VillinCre:Men1FL/FL:Sst-/- mice or C57BL/6 mice (controls), with or without inhibition of gastric acid by omeprazole. Primary …

Identity-By-Descent Mapping Identifies Major Locus For Serum Triglycerides In Amerindians Largely Explained By An Apoc3 Founder Mutation, Wen-Chi Hsueh, Anup K. Nair, Sayuko Kobes, Peng Chen, Harald H. H. Goring, Toni I. Pollin, Alka Malhotra, William C. Knowler, Leslie J. Baier, Robert L. Hanson

School of Medicine Publications and Presentations

Background—Identity-by-descent (IBD) mapping using empirical estimates of IBD allele sharing may be useful for studies of complex traits in founder populations, where hidden relationships may augment the inherent genetic information that can be used for localization.

Methods and Results—Through IBD mapping, using ~400,000 SNPs, of serum lipid profiles we identified a major linkage signal for triglycerides (TG) in 1,007 Pima Indians (LOD=9.23, p=3.5×10−11 on chromosome 11q). In subsequent fine-mapping and replication association studies in ~7,500 Amerindians, we determined that this signal reflects effects of a loss-of-function Ala43Thr substitution in APOC3 (rs147210663) and 3 established functional SNPs in APOA5. …

Whole Genome Sequencing In Psychiatric Disorders: The Wgspd Consortium, Stephan J. Sanders, Benjamin M. Neale, Hailiang Huang, Donna M. Werling, Joon-Yong An, Shan Dong, Goncalo Abecasis, P. Alexander Arguello, John Blangero, Michael Boehnke

School of Medicine Publications and Presentations

As technology advances, whole genome sequencing (WGS) is likely to supersede other genotyping technologies. The rate of this change depends on its relative cost and utility. Variants identified uniquely through WGS may reveal novel biological pathways underlying complex disorders and provide high-resolution insight into when, where, and in which cell type these pathways are affected. Alternatively, cheaper and less computationally intensive approaches may yield equivalent insights. Understanding the role of rare variants in the noncoding gene-regulating genome, through pilot WGS projects, will be critical to determine which of these two extremes best represents reality. With large cohorts, well-defined risk loci, …

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 …

Genetic Variation And Gene Expression Across Multiple Tissues And Developmental Stages In A Non-Human Primate, Anna J. Jasinska, Ivette Zelaya, Susan K. Service, Christine B. Peterson, Rita M. Cantor, Oi-Wa Choi, Joseph Deyoung, Eleazar Eskin, Lynn A. Fairbanks, John Blangero, Thomas D. Dyer

School of Medicine Publications and Presentations

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral …

Transition From Pre-Diabetes To Diabetes And Predictors Of Risk In Mexican-Americans, Shenghui Wu, Joseph B. Mccormick, Joanne E. Curran, Susan P. Fisher-Hoch

School of Medicine Publications and Presentations

Background: No studies have examined risk factors for the transition from pre-diabetes to diabetes in populations with widespread obesity and diabetes. We determined proximal changes and factors affecting the transition among Mexican-Americans with pre-diabetes.

Methods: Participants with pre-diabetes (n=285) were recruited from our randomly sampled population-based Cameron County Hispanic Cohort. These participants were followed for an average of 27 months with repeat examination every 3 to 4 months. Metabolic health was defined as having less than 2 metabolic abnormalities (e.g., hypertension, elevated low-density lipoprotein, etc). Diabetes was identified as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% and/or on hypoglycemic …

Sex-Biased Microrna Expression In Mammals And Birds Reveals Underlying Regulatory Mechanisms And A Role In Dosage Compensation, Maria Warnefors, Katharina Mössinger, Jean Halbert, Anja Studer, Tania Studer, John L. Vandeberg, Isa Lindgren, Amir Fallahshahroudi, Per Jensen, Henrik Kaessmann

School of Medicine Publications and Presentations

Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that …

Trak2, A Novel Regulator Of Abca1 Expression, Cholesterol Efflux And Hdl Biogenesis, Nicole J. Lake, Rachael L. Taylor, Hugh Trahair, K. N. Harikrishnan, Joanne E. Curran, Marcio Almeida, Hemant Kulkarni, Matthew P. Johnson, Thomas D. Dyer, Michael Mahaney, Harald H. H. Goring, John Blangero

School of Medicine Publications and Presentations

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.

Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the …

Rare, Potentially Pathogenic Variants In Znf469 Are Not Enriched In Keratoconus In A Large Australian Cohort Of European Descent, Sionne E. M. Lucas, Tiger Zhou, Nicholas B. Blackburn, Richard A. Mills, Jonathan Ellis, Paul Leo, Emmanuelle Souzeau, Bronwyn Ridge, Jac C. Charlesworth, Matthew A. Brown

School of Medicine Publications and Presentations

Purpose: The Zinc Finger Protein 469 (ZNF469) gene has been proposed as a candidate gene for keratoconus due to the association of an upstream polymorphism (rs9938149) with the disease in two independent studies, and the role of the gene in the autosomal recessive disease Brittle Cornea Syndrome. Coding variants in ZNF469 have been assessed for association with keratoconus in several small studies, with conflicting results. We assessed rare, potentially pathogenic variants in ZNF469 for enrichment in keratoconus patients in a cohort larger than all previous studies combined.

Methods: ZNF469 was sequenced in 385 Australian keratoconus patients of European …

Tc-Ptp Nuclear Trafficking In Keratinocytes, Mihwa Kim, Liza D. Morales, Dae Joon Kim

School of Medicine Publications and Presentations

No abstract provided.

Protein Tyrosine Signaling And Its Potential Therapeutic Implications In Carcinogenesis, Mihwa Kim, Minwoo Baek, Dae Joon Kim

School of Medicine Publications and Presentations

Protein tyrosine phosphorylation is a crucial signaling mechanism that plays a role in epithelial carcinogenesis. Protein tyrosine kinases (PTKs) control various cellular processes including growth, differentiation, metabolism, and motility by activating major signaling pathways including STAT3, AKT, and MAPK. Genetic mutation of PTKs and/or prolonged activation of PTKs and their downstream pathways can lead to the development of epithelial cancer. Therefore, PTKs became an attractive target for cancer prevention. PTK inhibitors are continuously being developed, and they are currently used for the treatment of cancers that show a high expression of PTKs. Protein tyrosine phosphatases (PTPs), the homeostatic counterpart of …

Phosphoproteomics Profiling Of Nonsmall Cell Lung Cancer Cells Treated With A Novel Phosphatase Activator, Danica Wiredja, Marzieh Ayati, Sahar Mazhar, Jaya Sangodkar, Sean Maxwell, Daniela Schlatzer, Goutham Narla, Mehmet Koyutürk, Mark R. Chance

Computer Science Faculty Publications and Presentations

Activation of protein phosphatase 2A (PP2A) is a promising anti-cancer therapeutic strategy, as this tumor suppressor has the ability to coordinately downregulate multiple pathways involved in the regulation of cellular growth and proliferation. In order to understand the systems-level perturbations mediated by PP2A activation, we carried out mass spectrometry-based phosphoproteomic analysis of two KRAS mutated non-small cell lung cancer (NSCLC) cell lines (A549 and H358) treated with a novel Small Molecule Activator of PP2A (SMAP). Overall, this permitted quantification of differential signaling across over 1,600 phosphoproteins and 3,000 phosphosites. Kinase activity assessment and pathway enrichment implicated collective downregulation of RAS …

Co-Independent Modification Of K+ Channels By Tricarbonyldichlororuthenium(Ii) Dimer (Corm-2), Guido Gessner, Nirakar Sahoo, Sandip M. Swain, Gianna Hirth, Roland Schönherr, Ralf Mede, Matthias Westerhausen, Hans Henning Brewitz, Pascal Heimer, Diana Imhof

Biology Faculty Publications and Presentations

Although toxic when inhaled in high concentrations, the gas carbon monoxide (CO) is endogenously produced in mammals, and various beneficial effects are reported. For potential medicinal applications and studying the molecular processes underlying the pharmacological action of CO, so-called CO-releasing molecules (CORMs), such as tricabonyldichlororuthenium(II) dimer (CORM-2), have been developed and widely used. Yet, it is not readily discriminated whether an observed effect of a CORM is caused by the released CO gas, the CORM itself, or any of its intermediate or final breakdown products. Focusing on Ca2+- and voltage-dependent K+ channels (KCa1.1) and voltage-gated K+ channels (Kv1.5, Kv11.1) relevant …

Associations Between Self-Reported Sleep Quality And White Matter In Community-Dwelling Older Adults: A Prospective Cohort Study, Claire E. Sexton, Enikő Zsoldos, Nicola Filippini, Ludovica Griffanti, Anderson M. Winkler, Abda Mahmood, Charlotte L. Allan, Anya Topiwala, Simon D. Kyle, Kai Spiegelhalder

School of Medicine Publications and Presentations

Both sleep disturbances and decline in white matter microstructure are commonly observed in ageing populations, as well as in age-related psychiatric and neurological illnesses. A relationship between sleep and white matter microstructure may underlie such relationships, but few imaging studies have directly examined this hypothesis. In a study of 448 community-dwelling members of the Whitehall II Imaging Sub-Study aged between 60 and 82 years (90 female, mean age 69.2 ± 5.1 years), we used the magnetic resonance imaging technique diffusion tensor imaging to examine the relationship between self-reported sleep quality and white matter microstructure. Poor sleep quality at the time …

Prevalence Of Aflatoxin-Associated Tp53r249s Mutation In Hepatocellular Carcinoma In Hispanics In South Texas, Jingjing Jiao, Weibo Niu, Ying Wang, Keith Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica Michelle Betancourt-Garcia, R. Armour Forse, Joseph B. Mccormick, Susan P. Fisher-Hoch

School of Medicine Publications and Presentations

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation …

Uvb-Induced Nuclear Translocation Of Tc-Ptp By Akt/14-3-3Σ Axis Inhibits Keratinocyte Survival And Proliferation, Mihwa Kim, Liza D. Morales, Minwoo Baek, Thomas J. Slaga, John Digiovanni, Dae Joon Kim

School of Medicine Publications and Presentations

Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. …

“Yes, And …” Exploring The Future Of Learning Analytics In Medical Education, Matt M. Cirigliano, Charlie Guthrie, Martin V. Pusic, Anna T. Cianciolo, Jennifer E. Lim-Dunham, Anderson Spickard Iii, Valerie Terry

School of Medicine Publications and Presentations

This Conversations Starter article presents a selected research abstract from the 2017 Association of American Medical Colleges Northeastern Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the study. Commentators brainstormed “what's next” with learning analytics in medical education, including advancements in interaction metrics and the use of interactivity analysis to deepen understanding of perceptual, cognitive, and social learning and transfer processes.

Mobility Limitations And Fear Of Falling In Non-English Speaking Older Mexican-Americans, Eric G. James, Phillip Conatser, Murat Karabulut, Suzanne G. Leveille, Jeffrey M. Hausdorff, Sarah Cote, Katherine L. Tucker, Bruce Barton, Jonathan F. Bean, Soham Al Snih, Kyriakos S. Markides

Health & Human Performance Faculty Publications and Presentations

Objective—To determine whether older Mexican-Americans who cannot speak and/or understand spoken English have higher rates of mobility limitations or fear of falling than their English-speaking counterparts.

Design—We conducted a cross-sectional analysis of 1169 community-dwelling MexicanAmericans aged 72–96 years from the 2000–2001 wave of the Hispanic Established Population for the Epidemiological Study of the Elderly. Mobility limitations were defined as having a Short Physical Performance Battery score ≤9, and fear of falling by participant report of being somewhat, fairly, or very afraid of falling. We determined the rates and odds ratios, for having mobility limitations and fear of falling …

Mobility Limitations And Fear Of Falling In Non-English Speaking Older Mexican-Americans, Eric G. James, Phillip Conatser, Murat Karabulut, Suzanne G. Leveille, Jeffrey M. Hausdorff, Sarah Cote, Katherine L. Tucker, Bruce Barton, Jonathan F. Bean, Soham Al Snih, Kyriakos S. Markides

Health & Human Performance Faculty Publications and Presentations

Objective

To determine whether older Mexican-Americans who cannot speak and/or understand spoken English have higher rates of mobility limitations or fear of falling than their English-speaking counterparts.

Design

We conducted a cross-sectional analysis of 1169 community-dwelling Mexican-Americans aged 72–96 years from the 2000–2001 wave of the Hispanic Established Population for the Epidemiological Study of the Elderly. Mobility limitations were defined as having a Short Physical Performance Battery score ≤9, and fear of falling by participant report of being somewhat, fairly, or very afraid of falling. We determined the rates and odds ratios, for having mobility limitations and fear of falling …

24-Hour Blood Pressure Variability Assessed By Average Real Variability: A Systematic Review And Meta-Analysis, Luis J. Mena, Vanessa G. Felix, Jesus D. Melgarejo, Gladys E. Maestre

School of Medicine Publications and Presentations

Background-—Although 24-hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24-hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24-hour BPV, including the average real variability (ARV) index.

Methods and Results-—Studies chosen for review were those that presented data for 24-hour BPV in adults from meta-analysis, longitudinal or cross-sectional design, and examined BPV in terms …

Acute Maternal Oxidant Exposure Causes Susceptibility Of The Fetal Brain To Inflammation And Oxidative Stress, Feroz Akhtar, Christopher A. Rouse, Gabriel Catano, Marcus Montalvo, Sarah L. Ullevig, Reto Asmis, Kusum Kharbanda, Shivani K. Maffi

School of Medicine Publications and Presentations

Background

Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive.

Methods

Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) …

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 …

Reduction Of Cognitive Decline In Patients With Or At High Risk For Diabetes, Gladys E. Maestre

School of Medicine Publications and Presentations

Purpose of review—The incidence of Alzheimer’s disease and related disorders is expected to triple by 2050. People with type 2 diabetes and prediabetes have a higher risk of cognitive dysfunction, including Alzheimer’s disease and vascular dementia. Controversy remains about when and how to prevent and treat cognitive dysfunction in people with or at high risk of diabetes.

Recent findings—In our review of ongoing clinical trials, we have found that there has been an increase in the number of studies assessing the efficacy of pharmacological and non-pharmacological approaches to prevent or slow down cognitive impairment among people with or …

Detection And Risk Stratification Of Women At High Risk Of Preterm Birth In Rural Communities Near Nagpur, India, Archana Patel, Amber Abhijeet Prakash, Yamini V. Pusdekar, Hemant Kulkarni, Patricia Hibberd

School of Medicine Publications and Presentations

Background: Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB.

Methods: Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community …

Ontogeny Of Myosin Isoform Expression And Prehensile Function In The Tail Of The Gray Short-Tailed Opossum ( Monodelphis Domestica), Dylan R. Thomas, Brad A. Chadwell, Gary R. Walker, Julio E. Budde, John L. Vandeberg, Michael T. Butcher

School of Medicine Publications and Presentations

Terrestrial opossums use their semiprehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 mo, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3-7 mo) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and -2B, which will transition into greater MHC-1β and -2A isoform content …

Benchmarking Relatedness Inference Methods With Genome-Wide Data From Thousands Of Relatives, Monica D. Ramstetter, Thomas D. Dyer, Donna M. Lehman, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Jason G. Mezey, Amy L. Williams

School of Medicine Publications and Presentations

Inferring relatedness from genomic data is an essential component of genetic association studies, population genetics, forensics, and genealogy. While numerous methods exist for inferring relatedness, thorough evaluation of these approaches in real data has been lacking. Here, we report an assessment of 12 state-of-the-art pairwise relatedness inference methods using a data set with 2485 individuals contained in several large pedigrees that span up to six generations. We find that all methods have high accuracy (92–99%) when detecting first- and second-degree relationships, but their accuracy dwindles to76% of relative pairs. Overall, the most accurate methods are Estimation of Recent Shared Ancestry …

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 …