Medicine and Health Sciences Commons^™

Lack Of Association Between Slc30a8 Variants And Type 2 Diabetes In Mexican American Families, Hemant Kulkarni, Manju Mamtani, Juan M. Peralta, Vincent P. Diego, Thomas D. Dyer, Harald H. H. Goring, Laura Almasy, Sarah Williams-Blangero, Michael C. Mahaney, Ravindranath Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications

SLC30A8 encodes zinc transporter 8 which is involved in packaging and release of insulin. Evidence for the association of SLC30A8 variants with type 2 diabetes (T2D) is inconclusive. We interrogated single nucleotide polymorphisms (SNPs) around SLC30A8 for association with T2D in high-risk, pedigreed individuals from extended Mexican American families. This study of 118 SNPs within 50 kb of the SLC30A8 locus tested the association with eight T2D-related traits at four levels: (i) each SNP using measured genotype approach (MGA); (ii) interaction of SNPs with age and sex; (iii) combinations of SNPs using Bayesian Quantitative Trait Nucleotide (BQTN) analyses; and (iv) …

Constrained Multivariate Association With Longitudinal Phenotypes, Phillip E. Melton, Juan M. Peralta, Laura Almasy

School of Medicine Publications

The incorporation of longitudinal data into genetic epidemiological studies has the potential to provide valuable information regarding the effect of time on complex disease etiology. Yet, the majority of research focuses on variables collected from a single time point. This aim of this study was to test for main effects on a quantitative trait across time points using a constrained maximum-likelihood measured genotype approach. This method simultaneously accounts for all repeat measurements of a phenotype in families. We applied this method to systolic blood pressure (SBP) measurements from three time points using the Genetic Analysis Workshop 19 (GAW19) whole-genome sequence …

Finding Potential Cis-Regulatory Loci Using Allele-Specific Chromatin Accessibility As Weights In A Kernel-Based Variance Component Test, Juan M. Peralta, Marcio A. Almeida, Lawrence J. Abraham, Eric K. Moses, John Blangero

School of Medicine Publications

We present a novel approach to detect potential cis-acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against expression phenotypes. To test our method we used public ENCODE whole genome DNase-I sequencing data, from a single sample, to estimate the functional potentials of the subset of 10,552 noncoding heterozygous single-nucleotide polymorphisms (SNPs) that were also present in the Genetic Analysis Workshop 19 (GAW19) family-based data set. We then built two covariance kernels, one nonweighted and one weighted by the functional potentials, and …

Genetic Analysis Workshop 19: Methods And Strategies For Analyzing Human Sequence And Gene Expression Data In Extended Families And Unrelated Individuals, Corinne D. Engelman, Celia M T Greenwood, Julia N. Bailey, Rita M. Cantor, Jack W. Kent Jr, Inke R. König, Justo Lorenzo Bermejo, Phillip E. Melton, Stephanie A. Santorico, Laura Almasy

School of Medicine Publications

Genetic Analysis Workshop 19 provided a platform for developing and evaluating statistical methods to analyze whole-genome sequence and gene expression data from a pedigree-based sample, as well as whole-exome sequence data from a large cohort of unrelated individuals. In this article we present an overview of the data sets, the GAW experience, and summaries of the contributions arranged into nine methodological themes.

Novel Genetic Loci Underlying Human Intracranial Volume Identified Through Genome-Wide Association, Hieab Hh Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Rentería, Stella Trompet, John Blangero, Joanne E. Curran, Ravi Duggirala, Harald Hh Goring

School of Medicine Publications

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci …

N-Acetylcysteine In Combination With Igf-1 Enhances Neuroprotection Against Proteasome Dysfunction-Induced Neurotoxicity In Sh-Sy5y Cells, Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, Virginia L. Scofield

School of Medicine Publications

Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson’s disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase …

Distribution Of Six Polymorphisms In Two Communities With A Historical High Incidence Of Diabetes And Obesity In Yucatan, Mexico, Miriam Givisay Domínguez-Cruz, María De Lourdes Muñoz, Armando Totomoch-Serra, María Guadalupe García-Escalante, Nina Valadez-González, Doris Pinto-Escalante, Alvaro Diaz-Badillo

School of Medicine Publications

Aims: Maya ancestry populations from Yucatan have exhibited a high prevalence of diabetes and obesity; consequently, the aim of this study was to determine the allelic and genotype frequencies of six polymorphisms associated with diabetes and obesity in two Maya populations.

Place and Duration of Study: Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN; Laboratorios de Genética y Hematología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán between September 2014 and March 2016.

Methodology: Healthy individuals with Maya ancestry were recruited in small rural and urban communities from Yucatan. Six …

Methylation Of Socs3 Is Inversely Associated With Metabolic Syndrome In An Epigenome-Wide Association Study Of Obesity, Omar Ali, Diana Cerjak, Jack W. Kent Jr, Roland James, John Blangero, Melanie A. Carless, Yi Zhang

School of Medicine Publications

Epigenetic mechanisms, including DNA methylation, mediate the interaction between gene and environment and may play an important role in the obesity epidemic. We assessed the relationship between DNA methylation and obesity in peripheral blood mononuclear cells (PBMCs) at 485,000 CpG sites across the genome in family members (8-90 y of age) using a discovery cohort (192 individuals) and a validation cohort (1,052 individuals) of Northern European ancestry. After Bonferroni-correction (Pα=0.05 = 1.31 × 10-7) for genome-wide significance, we identified 3 loci, cg18181703 (SOCS3), cg04502490 (ZNF771), and cg02988947 (LIMD2), where methylation status was associated with body mass index percentile (BMI%), a …

The Genetic Architecture Of Type 2 Diabetes, Christian Fuchsberger, Jason Flannick, Tanya M. Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J. Gaulton, Joanne E. Curran, Satish Kumar, John Blangero, Ravi Duggirala

School of Medicine Publications

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping …

Reproductive Health Knowledge Among African American Women Enrolled In A Clinic-Based Randomized Controlled Trial To Reduce Psychosocial And Behavioral Risk, Project Dc-Hope, Uba Backonja, Candace Robledo, Maeve Wallace, Katrina F. Flores, Michele Kiely

School of Medicine Publications

Background: Washington, DC, has among the highest rates of sexually transmitted infections and unintended pregnancy in the United States. Increasing women's reproductive health knowledge may help to address these reproductive health issues. This analysis assessed whether high-risk pregnant African American women in Washington, DC, who participated in an intervention to reduce behavioral and psychosocial risks had greater reproductive health knowledge than women receiving usual care.

Methods: Project DC-HOPE was a randomized, controlled trial that included pregnant African American women in Washington, DC, recruited during prenatal care (PNC). Women in the intervention group were provided reproductive health education and received tailored …

Genome-Wide Significant Loci For Addiction And Anxiety, Karen Hodgson, Laura Almasy, Emma E. M. Knowles, Jack W. Kent Jr., Joanne E. Curran, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Peter T. Fox, Godfrey D. Pearlson, J. H. Krystal, Ravindranath Duggirala, John Blangero, David C. Glahn

School of Medicine Publications

Background

Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology.

Methods

Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing …

Preterm Birth And Air Pollution: Critical Windows Of Exposure For Women With Asthma, Pauline Mendola, Maeve Wallace, Beom Seuk Hwang, Danping Liu, Candace Robledo, Tuija Männistö

School of Medicine Publications

Background: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied.

Objective: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk.

Methods: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate …

Psma Targeted Docetaxel-Loaded Superparamagnetic Iron Oxide Nanoparticles For Prostate Cancer, Prashanth K. B. Nagesh, Nia R. Johnson, Vijaya K. N. Boya, Pallabita Chowdhury, Shadi F. Othman, Vahid Khalilzad-Sharghi, Bilal B. Hafeez, Aditya Ganju, Sheema Khan, Stephen Behrman, Nadeem Zafar, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Docetaxel (Dtxl) is currently the most common therapeutic option for prostate cancer (PC). However, adverse side effects and problems associated with chemo-resistance limit its therapeutic outcome in clinical settings. A targeted nanoparticle system to improve its delivery to and activity at the tumor site could be an attractive strategy for PC therapy. Therefore, the objective of this study was to develop and determine the anti-cancer efficacy of a novel docetaxel loaded, prostate specific membrane antigen (PSMA) targeted superparamagnetic iron oxide nanoparticle (SPION) (J591-SPION-Dtxl) formulation for PC therapy. Our results showed the SPION-Dtxl formulation exhibits an optimal particle size and zeta …

Cordycepin Promotes Apoptosis By Modulating The Erk-Jnk Signaling Pathway Via Dusp5 In Renal Cancer Cells, Jung-Hoo Hwang, Jong Cheon Joo, Dae Joon Kim, Eunbi Jo, Hwa-Seung Yoo, Kyung-Bok Lee, Soo Jung Park, Ik-Soon Jang

School of Medicine Publications

Constitutive activation of extracellular signal regulated kinase (ERK)-Jun NH2-terminal kinase (JNK) signaling commonly occurs in tumors. The activation of ERK promotes cell proliferation, whereas that of JNK induces cell apoptosis. However, the apoptotic mechanism of ERK-JNK signaling in cancer is not well understood. Recently, we identified that apoptosis and activation of the JNK signaling pathway were induced after cordycepin treatment in human renal cancer, suggesting that JNK signaling might contribute to TK-10 cell apoptosis. We investigated the apoptotic effects of cordycepin by evaluating the activation of the ERK-JNK signaling pathway in renal cancer TK-10 cells. We found that cordycepin downregulated …

The Integration Of Quantitative Genetics, Paleontology, And Neontology Reveals Genetic Underpinnings Of Primate Dental Evolution, Leslea J. Hlusko, Christopher A. Schmitt, Tesla A. Monson, Marianne F. Brasil, Michael Mahaney

School of Medicine Publications

Significance

Experimental research on mice has yielded tremendous biological insight. However, the ∼140 million y of evolution that separate mice from humans pose a hurdle to direct application of this knowledge to humans. We report here that considerable progress for identifying genetically patterned skeletal phenotypes beyond the mouse model is possible through transdisciplinary approaches that include the anatomical sciences. Indeed, anatomy and paleontology offer unique opportunities through which to develop and test hypotheses about the underlying genetic mechanisms of the skeleton for taxa that are not well suited to experimental manipulation, such as ourselves.

Abstract

Developmental genetics research on mice …

Air Pollution Exposure And Preeclampsia Among Us Women With And Without Asthma, Pauline Mendola, Maeve Wallace, Danping Liu, Candace Robledo, Tuija Männistö, Katherine Grantz

School of Medicine Publications

Maternal asthma and air pollutants have been independently associated with preeclampsia but rarely studied together. Our objective was to comprehensively evaluate preeclampsia risk based on the interaction of maternal asthma and air pollutants. Preeclampsia and asthma diagnoses, demographic and clinical data came from electronic medical records for 210,508 singleton deliveries. Modified Community Multiscale Air Quality models estimated preconception, first and second trimester and whole pregnancy exposure to: particulate matter (PM)<2.5 and <10µm, ozone, nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO); PM2.5 constituents; volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Asthma-pollutant interaction adjusted relative risks (RR) and 95% confidence intervals (CI) for preeclampsia were calculated by interquartile range for criteria pollutants and high exposure (≥75th percentile) for PAHs and VOCs. Asthmatics had higher risk associated with first trimester NOx and SO2 and whole pregnancy elemental carbon (EC) exposure than non-asthmatics, but only EC significantly increased risk (RR=1.11, CI:1.03-1.21). Asthmatics also had a 10% increased risk associated with second trimester CO. Significant interactions were observed for nearly all VOCs and asthmatics had higher risk during all time windows for benzene, ethylbenzene, m-xylene, o-xylene, p-xylene and toluene while most PAHs did not increase risk.

Prosaposin Is A Regulator Of Progranulin Levels And Oligomerization, Alexandra M. Nicholson, Nicole A. Finch, Marcio Almeida, Ralph B. Perkerson, Marka Van Blitterswijk, Aleksandra Wojtas, Basar Cenik, Laura Almasy, Thomas D. Dyer, Juan M. Peralta, Joanne E. Curran, Donna M. Lehman, Ravindranath Duggirala, John Blangero

School of Medicine Publications

Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer’s and Parkinson’s disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas …

Progressive Bidirectional Age-Related Changes In Default Mode Network Effective Connectivity Across Six Decades, Karl Li, Angela R. Laird, Larry R. Price, D. Reese Mckay, John Blangero, David C. Glahn, Peter T. Fox

School of Medicine Publications

The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade …

Utility Of Lymphoblastoid Cell Lines For Induced Pluripotent Stem Cell Generation, Satish Kumar, Joanne E. Curran, David C. Glahn, John Blangero

School of Medicine Publications

A large number of EBV immortalized LCLs have been generated and maintained in genetic/epidemiological studies as a perpetual source of DNA and as a surrogate in vitro cell model. Recent successes in reprograming LCLs into iPSCs have paved the way for generating more relevant in vitro disease models using this existing bioresource. However, the overall reprogramming efficiency and success rate remain poor and very little is known about the mechanistic changes that take place at the transcriptome and cellular functional level during LCL-to-iPSC reprogramming. Here, we report a new optimized LCL-to-iPSC reprogramming protocol using episomal plasmids encoding pluripotency transcription factors …

The Arg59trp Variant In Angptl8 (Betatrophin) Is Associated With Total And Hdl-Cholesterol In American Indians And Mexican Americans And Differentially Affects Cleavage Of Angptl3, Robert L. Hanson, Fatjon Leti, Darwin Tsinajinnie, Sayuko Kobes, Sobha Puppala, Joanne E. Curran, Laura Almasy, Donna M. Lehman, John Blangero, Ravi Duggirala, Johanna K. Distefano

School of Medicine Publications

We previously identified a locus linked to total cholesterol (TC) concentration in Pima Indians on chromosome 19p. To characterize this locus, we genotyped >2000 SNPs in 1838 Pimas and assessed association with log(TC). We observed evidence for association with log(TC) with rs2278426 (3.5% decrease/copy of the T allele; P=5.045×10(-6)) in the ANGPTL8 (angiopoietin-like 8) gene. We replicated this association in 2413 participants of the San Antonio Mexican American Family Study (SAMAFS: 2.0% decrease per copy of the T allele; P=0.005842). In a meta-analysis of the combined data, we found the strongest estimated effect with rs2278426 (P=2.563×10(-7)). The variant T allele …

Transancestral Fine-Mapping Of Four Type 2 Diabetes Susceptibility Loci Highlights Potential Causal Regulatory Mechanisms, Momoko Horikoshi, Lorenzo Pasquali, Steven Wiltshire, Jeroen R. Huyghe, Anubha Mahajan, Jennifer L. Asimit, John Blangero

School of Medicine Publications

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised …

Investigation Of Genetic Variation Underlying Central Obesity Amongst South Asians, William R. Scott, Weihua Zhang, Marie Loh, Sian-Tsung Tan, Benjamin Lehne, Uzma Azfal, Juan M. Peralta, Richa Saxena, Sarju Ralhan, Gurpreet S. Wander

School of Medicine Publications

South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of …

Tissue-Specific Conditional Pkcε Knockout Mice: A Model To Precisely Reveal Pkcε Functional Role In Initiation, Promotion And Progression Of Cancer, Bilal B. Hafeez, Louise Meske, Ashok Singh, Anupama Singh, Weixiong Zhong, Patricia Powers, Manorama John, Anne E. Griep, Ajit K. Verma

School of Medicine Publications

PKCε is a transforming oncogene and a predictive biomarker of various human cancers. However, a precise in vivo link of PKCε to cancer induction, progression and metastasis remain undefined. To achieve these goals, we generated tissue specific conditional PKCε knockout mice (PKCε-CKO) using cre-lox technology. Homozygous PKCε^LoxP/LoxP mice have normal body weight and phenotype. To determine what effect loss of PKCε would have on the prostate, the PKCε^LoxP/LoxP mice were bred to probasin cre (PB-Cre4⁺) mice which express cre specifically in the prostate epithelium of postnatal mice. Western blot and immunohistochemical analyses showed reduced levels of …

Genome-Wide Association Studies Suggest Sex-Specific Loci Associated With Abdominal And Visceral Fat, Yun Ju Sung, L. Pérusse, M. A. Sarzynski, M. Fornage, S. Sidney, B. Sternfeld, T. Rice, J. G. Terry, D. R. Jacobs Jr., John Blangero, Joanne E. Curran

School of Medicine Publications

Background:

To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).

Subjects and Methods:

Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. …

Non-Parametric Combination And Related Permutation Tests For Neuroimaging, Anderson M. Winkler, Matthew A. Webster, Jonathan C. Brooks, Irene Tracey, Stephen M. Smith, Thomas E. Nichols

School of Medicine Publications

In this work, we show how permutation methods can be applied to combination analyses such as those that include multiple imaging modalities, multiple data acquisitions of the same modality, or simply multiple hypotheses on the same data. Using the well-known definition of union-intersection tests and closed testing procedures, we use synchronized permutations to correct for such multiplicity of tests, allowing flexibility to integrate imaging data with different spatial resolutions, surface and/or volume-based representations of the brain, including non-imaging data. For the problem of joint inference, we propose and evaluate a modification of the recently introduced non-parametric combination (NPC) methodology, such …

A Unique Patient With Epilepsy With Cinematographic Visual Hallucinations, Alexis E. Nelson, Frank G. Gilliam, Jayant Acharya, Sabina Miranda

School of Medicine Publications

Purpose

The purpose of this case report is to document a patient with cinematographic hallucinations, with corresponding right temporal lobe seizures on electroencephalogram (EEG).

Results

The results showed that the patient's EEG was normal. The patient subsequently reported hallucinations, which had been occurring for the last several months. During monitoring, no interictal EEG abnormalities were identified, but a total of 11 partial seizures were captured originating from the right posterior temporal area. They either were subclinical or corresponded with his visual hallucinations.

Conclusion

The present study demonstrates focal seizures of temporal lobe origin producing complex visual hallucinations without a corresponding …

Gwas And Transcriptional Analysis Prioritize Itpr1 And Cntn4 For A Serum Uric Acid 3p26 Qtl In Mexican Americans, Geetha Chittoor, Jack W. Kent Jr., Marcio Almeida, Sobha Puppala, Vidya S. Farook, Shelley A. Cole, Karin Haack, Harald H. H. Goring, Jean W. Maccluer, Joanne E. Curran, Melanie A. Carless, Matthew P. Johnson, Eric K. Moses, Laura Almasy, Michael C. Mahaney, Donna M. Lehman, Ravindranath Duggirala, Anthony G. Comuzzie, John Blangero, Venkata Saroja Voruganti

School of Medicine Publications

Background: The variation in serum uric acid concentrations is under significant genetic influence. Elevated SUA concentrations have been linked to increased risk for gout, kidney stones, chronic kidney disease, and cardiovascular disease whereas reduced serum uric acid concentrations have been linked to multiple sclerosis, Parkinson’s disease and Alzheimer’s disease. Previously, we identified a novel locus on chromosome 3p26 affecting serum uric acid concentrations in Mexican Americans from San Antonio Family Heart Study. As a follow up, we examined genome-wide single nucleotide polymorphism data in an extended cohort of 1281 Mexican Americans from multigenerational families of the San Antonio Family Heart …

Soluble Forms Of Intercellular And Vascular Cell Adhesion Molecules Independently Predict Progression To Type 2 Diabetes In Mexican American Families, Hemant Kulkarni, Manju Mamtani, Juan M. Peralta, Marcio Almeida, Thomas D. Dyer, Harald H. H. Goring, Matthew P. Johnson, Ravindranath Duggirala, Michael C. Mahaney, Rene L. Olvera, Laura Almasy, David C. Glahn, Sarah Williams-Blangero, Joanne E. Curran, John Blangero

School of Medicine Publications

Objective: While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D.

Methods: Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These …

Ipsilesional Anodal Tdcs Enhances The Functional Benefits Of Rehabilitation In Patients After Stroke, Claire Allman, Ugwechi Amadi, Anderson M. Winkler, Leigh Wilkins, Nicola Filippini, Udo Kischka, Charlotte J. Stagg, Heidi Johansen-Berg

School of Medicine Publications

Anodal transcranial direct current stimulation (tDCS) can boost the effects of motor training and facilitate plasticity in the healthy human brain. Motor rehabilitation depends on learning and plasticity, and motor learning can occur after stroke. We tested whether brain stimulation using anodal tDCS added to motor training could improve rehabilitation outcomes in patients after stroke. We performed a randomized, controlled trial in 24 patients at least 6 months after a first unilateral stroke not directly involving the primary motor cortex. Patients received either anodal tDCS (n= 11) or sham treatment (n= 13) paired with daily motor training for 9 days. …

Furanodiene Alters Mitochondrial Function In Doxorubicin-Resistant Mcf-7 Human Breast Cancer Cells In An Ampk-Dependent Manner, Zhang-Feng Zhong, Wen Tan, William W. Qiang, Virginia L. Scofield, Ke Tian, Chun-Ming Wang, Wen-An Qiang, Yi-Tao Wang

School of Medicine Publications

Furanodiene is a bioactive sesquiterpene isolated from the spice-producing Curcuma wenyujin plant (Y. H. Chen and C. Ling) (C. wenyujin), which is a commonly prescribed herb used in clinical cancer therapy by modern practitioners of traditional Chinese medicine. Previously, we have shown that furanodiene inhibits breast cancer cell growth both in vitro and in vivo, however, the mechanism for this effect is not yet known. In this study, therefore, we asked (1) whether cultured breast cancer cells made resistant to the chemotherapeutic agent doxorubicin (DOX) via serial selection protocols are susceptible to furanodiene's anticancer effect, and (2) …