Medicine and Health Sciences Commons^™

Schizophrenia Gene Networks And Pathways And Their Applications For Novel Candidate Gene Selection, Jingchun Sun, Peilin Jia, Ayman H. Fanous, Edwin Van Den Oord, Xiangning Chen, Brien P. Riley, Richard L. Amdur, Kenneth S. Kendler, Zhongming Zhao

Psychiatry Publications

Background

Schizophrenia (SZ) is a heritable, complex mental disorder. We have seen limited success in finding causal genes for schizophrenia from numerous conventional studies. Protein interaction network and pathway-based analysis may provide us an alternative and effective approach to investigating the molecular mechanisms of schizophrenia.

Methodology/Principal Findings

We selected a list of schizophrenia candidate genes (SZGenes) using a multi-dimensional evidence-based approach. The global network properties of proteins encoded by these SZGenes were explored in the context of the human protein interactome while local network properties were investigated by comparing SZ-specific and cancer-specific networks that were extracted from the human interactome. …

Metabolic Oscillations In Pancreatic Islets Depend On The Intracellular Ca2+ Level But Not Ca2+ Oscillations, Matthew J. Merrins, Bernard Fendler, Min Zhang, Arthur Sherman, Richard Bertram, Leslie S. Satin

Pharmacology and Toxicology Publications

Abstract

Plasma insulin is pulsatile and reflects oscillatory insulin secretion from pancreatic islets. Although both islet Ca²⁺ and metabolism oscillate, there is disagreement over their interrelationship, and whether they can be dissociated. In some models of islet oscillations, Ca²⁺ must oscillate for metabolic oscillations to occur, whereas in others metabolic oscillations can occur without Ca²⁺ oscillations. We used NAD(P)H fluorescence to assay oscillatory metabolism in mouse islets stimulated by 11.1 mM glucose. After abolishing Ca²⁺ oscillations with 200 μM diazoxide, we observed that oscillations in NAD(P)H persisted in 34% of islets (n = 101). …

A Transposon In Comt Generates Mrna Variants And Causes Widespread Expression And Behavioral Differences Among Mice, Zhengsheng Li, Megan K. Mulligan, Xusheng Wang, Michael F. Miles, Lu Lu, Robert W. Williams

Pharmacology and Toxicology Publications

Background

Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits.

Methodology/Principal Findings

We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 …

Strengthening Family Practices For Latino Families, Karen G. Chartier, Lirio K. Negroni, Michie N. Hesselbrock

Social Work Publications

The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9–12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto …

Ethnicity And Health Disparities In Alcohol Research, Karen G. Chartier, Raul Caetano

Social Work Publications

Recent advances in alcohol research continue to build our understanding of alcohol consumption and related consequences for U.S. ethnic minority groups. National surveys show variations across ethnicities in drinking, alcohol use disorders, alcohol problems, and treatment use. Higher rates of high-risk drinking among ethnic minorities are reported for Native Americans and Hispanics, although within-ethnic group differences (e.g., gender, age-group, and other subpopulations) also are evident for ethnicities. Whites and Native Americans have a greater risk for alcohol use disorders relative to other ethnic groups. However, once alcohol dependence occurs, Blacks and Hispanics experience higher rates than Whites of recurrent or …

Multiple Independent Loci At Chromosome 15q25.1 Affect Smoking Quantity: A Meta-Analysis And Comparison With Lung Cancer And Copd, Nancy L. Saccone, Robert C. Culverhouse, Tae-Hwi Schwantes-An, Dale S. Cannon, Xiangning Chen, Sven Cichon, Ina Giegling, Shizhong Han, Younghun Han, Kaisu Keskitalo-Vuokko, Xiangyang Kong, Maria T. Landi, Jennie Z. Ma, Susan E. Short, Sarah H. Stephens, Victoria L. Stevens, Lingwei Sun, Yufei Wang, Angela S. Wenzlaff, Steven H. Aggen, Naomi Breslau, Peter Broderick, Nilanjan Chatterjee, Jingchun Chen, Andrew C. Heath, Marku Heliovaara, Nicole R. Hoft, David J. Hunter, Majken K. Jensen, Nicholas G. Martin, Grant W. Montgomery, Tianhua Niu, Thomas J. Payne, Leena Peltonen, Michele L. Pergadia, John P. Rice, Richard Sherva, Margaret R. Spitz, Juzhong Sun, Jen C. Wang, Robert B. Weiss, William Wheeler, Stephanie H. Witt, Bao-Zhu Yang, Neil E. Caporaso, Marissa A. Ehringer, Tim Eisen, Susan M. Gapstur, Joel Gelemter, Richard Houlston, Jaakko Kaprio, Kenneth S. Kendler, Peter Kraft, Mark F. Leppert, Ming D. Li, Pamela A. F. Madden, Markus M. Nothen, Sreekumar Pillai, Marcella Rietschel, Dan Rujescu, Ann Schwartz, Christopher I. Amos, Laura J. Bierut

Psychiatry Publications

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary …

Pooled Protein Immunization For Identification Of Cell Surface Antigens In Streptococcus Sanguinis, Xiuchun Ge, Todd Kitten, Cindy L. Munro, Daniel H. Conrad, Ping Xu

Philips Institute for Oral Health Research Publications

Background

Available bacterial genomes provide opportunities for screening vaccines by reverse vaccinology. Efficient identification of surface antigens is required to reduce time and animal cost in this technology. We developed an approach to identify surface antigens rapidly inStreptococcus sanguinis, a common infective endocarditis causative species.

Methods and Findings

We applied bioinformatics for antigen prediction and pooled antigens for immunization. Forty-seven surface-exposed proteins including 28 lipoproteins and 19 cell wall-anchored proteins were chosen based on computer algorithms and comparative genomic analyses. Eight proteins among these candidates and 2 other proteins were pooled together to immunize rabbits. The antiserum reacted …

Transcriptomic Analysis Of The Venom Gland Of The Red-Headed Krait (Bungarus Flaviceps) Using Expressed Sequence Tags, Ang Swee Siang, Robin Doley, Freek J. Vonk, R. Manjunatha Kini

Biochemistry and Molecular Biology Publications

Background

The Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genus Bungarus have been well characterized, a detailed compositional analysis of B. flaviceps is currently lacking.

Results

Here, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of a B. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of β-bungarotoxin), phospholipase A …

Long-Term Fish Oil Supplementation Induces Cardiac Electrical Remodeling By Changing Channel Protein Expression In The Rabbit Model, Xulin Xu, Min Jiang, Yuhong Wang, Timothy Smith, Clive M. Baumgarten, Mark A. Wood, Gea-Ny Tseng

Physiology and Biophysics Publications

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography - mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of …

A Molecular Dynamics Investigation Of Lipid Bilayer Perturbation By Pip2, Dmitry Lupyan, Mihaly Mezei, Diomedes E. Logothetis, Roman Osman

Physiology and Biophysics Publications

Abstract

Phosphoinositides like phosphatidylinositol 4,5-bisphosphate (PIP₂) are negatively charged lipids that play a pivotal role in membrane trafficking, signal transduction, and protein anchoring. We have designed a force field for the PIP₂ headgroup using quantum mechanical methods and characterized its properties inside a lipid bilayer using molecular dynamics simulations. Macroscopic properties such as area/headgroup, density profiles, and lipid order parameters calculated from these simulations agree well with the experimental values. However, microscopically, the PIP₂ introduces a local perturbation of the lipid bilayer. The average PIP₂ headgroup orientation of 45° relative to the bilayer …

Increased Interleukin-6 Activity Associated With Painful Chemotherapy-Induced Peripheral Neuropathy In Women After Breast Cancer Treatment, Angela R. Starkweather

School of Nursing Publications

Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, ) or did not experience CIPN symptoms (Comparison group, ). CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R) compared to women without CIPN symptoms ( for both). In addition, soluble gp130, which blocks the IL-6/sIL-6R …

Rifaximin Treatment In Hepatic Encephalopathy, Nathan M. Bass, Kevin D. Mullen, Arun J. Sanyal, Fred Poordad, Guy Neff, Carroll B. Leevy, Samuel Sigal, Muhammad Y. Sheikh, Kimberly Beavers, Todd Frederick, Lewis Teperman, Donald Hillebrand, Shirley Huang, Kunal Merchant, Audrey Shaw, Enoch Bortey, William P. Forbes

Internal Medicine Publications

Background

Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established.

Methods

In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode …

Pioglitazone, Vitamin E, Or Placebo For Nonalcoholic Steatohepatitis, Arun J. Sanyal, Naga Chalasani, Kris V. Kowdley, Arthur Mccollough, Anna Mae Diehl, Nathan M. Bass, Brent A. Neuschwander-Tetri, Joel E. Lavine, James Tonascia, Aynur Unalp, Mark Van Natta, Jeanne Clark, Elizabeth M. Brunt, David E. Kleiner, Jay H. Hoofnagle, Patricia R. Robuck

Internal Medicine Publications

Background

Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease.

Methods

We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary …

Nuclear Expression Of Klf6 Tumor Suppressor Factor Is Highly Associated With Overexpression Of Erbb2 Oncoprotein In Ductal Breast Carcinomas, Ricardo C. Gehrau, Diego S. D'Astolfo, Catherine I. Dumur, Jose L. Bocco, Nicolas P. Koritschoner

Pathology Publications

Background

Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes.

Methodology/Principal Findings

In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues …

Making Informed Choices About Microarray Data Analysis, Mark A. Reimers

Biostatistics Publications

This article describes the typical stages in the analysis of microarray data for non-specialist researchers in systems biology and medicine. Particular attention is paid to significant data analysis issues that are commonly encountered among practitioners, some of which need wider airing. The issues addressed include experimental design, quality assessment, normalization, and summarization of multiple-probe data. This article is based on the ISMB 2008 tutorial on microarray data analysis. An expanded version of the material in this article and the slides from the tutorial can be found at http://www.people.vcu.edu/~mreimers/OGMDA/index.html.

Development And Vulnerability Factors In Adolescent Alcohol Use, Karen G. Chartier, Michie N. Hesselbrock, Victor M. Hesselbrock

Social Work Publications

This article provides an overview of the characteristics of adolescent alcohol use, normative and subgroup variations in drinking behavior, and important factors associated with an increased risk for developing alcohol problems in later adolescence and young adulthood. A parental/family history of alcoholism, temperament traits, conduct problems, cognitive functioning, alcohol expectancies, and peer and other social relations are identified as influencing an adolescent’s susceptibility for initiating a variety of alcohol use behaviors. The Deviance Prone Model, proposed by Sher (1991), is presented as an important tool for testing possible relationships among the various risk factors and their sequencing that leads to …

Alcohol Problems In Young Adults Transitioning From Adolescence To Adulthood: The Association With Race And Gender, Karen G. Chartier, Michie N. Hesselbrock, Victor M. Hesselbrock

Social Work Publications

Race and gender may be important considerations for recognizing alcohol related problems in Black and White young adults. This study examined the prevalence and age of onset of individual alcohol problems and alcohol problem severity across race and gender subgroups from a longitudinal study of a community sample of adolescents followed into young adulthood (N = 166; 23–29 yrs. old who were drinkers). All alcohol problems examined first occurred when subjects were in their late teens and early 20s. Drinking in hazardous situations, blackouts, and tolerance were the most common reported alcohol problems. In race and gender comparisons, more …

On Becoming Invisible, Edward F. Ansello

Director's Editorials from Age in Action

Age or impairment tends to render us less likely to be noticed. We can readjust how we see those becoming invisible.

Filling The Gap, Edward F. Ansello

Director's Editorials from Age in Action

There is need for multiple initiatives focusing on the pipeline from professional undergraduate education through the continuing education of current practitioners, in order to make some dent in the looming shortfall of geriatric health care providers. It is particularly gratifying to announce that Virginia has been awarded federal funding of a Geriatric Education Center (VGEC). The overall goal of the VGEC is to improve the training of health professionals in geriatrics.

The Blank Tablet Of Aging, Edward F. Ansello

Director's Editorials from Age in Action

The 16th annual conference of the Virginia Coalition for the Prevention of Elder Abuse (VCPEA) will include the basics of geriatric crisis assessment, depression and suicide among older adults; alcohol and medication misuse; older prisoners; training faith and community-based leaders to respond to domestic violence in later life; and brain injury in later life as a precipitant or a consequence of mistreatment. The Area Planning and Services Committee (APSC) conference will recognize the values, opportunities, and challenges associated with growing older with lifelong disabilities. These two conferences symbolize how we as a people can celebrate the good and confront the …

Aging As An Option, Edward F. Ansello

Director's Editorials from Age in Action

Sometimes people treat aging as if it were an option or a discretionary exercise. Aging is neither a fad nor an option but a bedrock reality that should be constantly under consideration, especially by those charged with protecting the common good. We need to remember that we should not treat aging and aging-related research, training, and services as an option.

Aging And The Behavioral Problems Of Brain Injury, Paul F. Aravich, Marylin Copeland

Case Studies from Age in Action

Educational Objectives

1. List the various classes of brain injury.

2. Identify cognitive and emotional problems as among the most common and disabling complications of brain injury.

3. Assess challenges to successful aging with a brain injury.

4. Examine the consequences of inadequate systems of care for the challenging behaviors produced by brain injury.

Senior Meal Programs: Feeding A Crowd With Local Foods, Gordon Walker, Elyse Thierry

Case Studies from Age in Action

Educational Objectives

1. Examine reasons for an institutional meal program to consider incorporating local food.

2. Identify potential community partners who might assist in moving such a program forward and the mutual benefits.

3. Describe the possible changes that an institution’s local food program can foster in the community at large.

Cpr And Dnr Decision Making, Viki Kind

Case Studies from Age in Action

Educational Objectives

1. Examine the complexities of end-of-life care and obstacles to good DNR decision making.

2. Discuss CPR and its perceived vs. actual chances for success.

3. Demonstrate best practices for communicating about CPR.

4. Consider how the signing of the DNR is just one component of endof- life care.

Reverse Mortgages, Bruce Desimone

Case Studies from Age in Action

Educational Objectives

1. Describe mobility rates among older adults.

2. Define a reverse mortgage and Home Equity Conversion Mortgage (HECM), and their origins in Virginia.

3. Explain key HECM loan and counseling features.

4. Illustrate how these features may improve the lives of older Virginians.

Racial Differences In Genetic And Environmental Risk To Preterm Birth, Timothy P. York, Jerome F. Strauss Iii, Michael C. Neale, Lindon J. Eaves

Human and Molecular Genetics Publications

Preterm birth is more prevalent in African Americans than European Americans and contributes to 3.4 times more African American infant deaths. Models of social inequity do not appreciably account for this marked disparity and molecular genetic studies have yet to characterize whether allelic differences that exist between races contribute to this gap. In this study, biometrical genetic models are applied to a large mixed-race sample consisting of 733,339 births to measure the extent that heritable factors and environmental exposures predict the timing of birth and explain differences between racial groups. Although we expected significant differences in mean gestational age between …

Development Of A Syngeneic Mouse Model Of Epithelial Ovarian Cancer, Bridget A. Quinn, Fang Xiao, Laura Bickel, Lainie Martin, Xiang Hua, Andres Klein-Szanto, Denise C. Connolly

Human and Molecular Genetics Publications

Background

Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies.

Methods

Individual lines of TgMISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (TgMISIIR-TAg-Low) were isolated that express the oncogenic transgene, but have little or no …

The Chinese Government's Response To Drug Use And Hiv/Aids: A Review Of Policies And Programs, Jianhu Li, Toan H. Ha, Cunmin Zhang, Hongjie Liu

Family Medicine and Population Health Publications

Illicit drug use has become popular in China. Acknowledging the challenge of illicit drug use, China has adopted several new policies on the management of illicit drug use in recent years. This study reviews the current policies on drug use and assesses the harm reduction interventions among drug users in China. The review documents that the new policies on drug use provide a variety of choices of detoxification treatment for drug users. The methadone maintenance treatment and needle exchange programs have been adopted as harm reduction models in China. Most of the reviewed harm reduction programs have been successfully implemented …

Does Chinese Culture Influence Psychosocial Factors For Heroin Use Among Young Adolescents In China? A Cross-Sectional Study, Hongjie Liu, Jian Li, Zhouping Lu, Wei Liu, Zhiyong Zhang

Family Medicine and Population Health Publications

Background

Little empirical research has examined how cultural factors influence psychosocial factors for heroin drug use. The objectives of the study were to investigate the levels of individualism and collectivism among young adolescents and how cultural differences were associated with the constructs of the Theory of Planned Behavior and other psychosocial factors for heroin drug use.

Methods

A cross-sectional study was conducted among young adolescents in an HIV and heroin-stricken area in China. The Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) was used to measure cultural norms and values in the context of three social groups: family members, close friends, and classmates. …

The Development Of A Web- And A Print-Based Decision Aid For Prostate Cancer Screening, Caroline S. Dorfman, Randi M. Williams, Elisabeth C. Kassan, Sara N. Red, David L. Dawson, William Tuong, Elizabeth R. Parker, Janet Ohene-Frempong, Kimberly M. Davis, Alexander H. Krist, Steven H. Woolf, Marc D. Schwartz, Mary B. Fishman, Carmella Cole, Kathryn L. Taylor

Family Medicine and Population Health Publications

Background Whether early detection and treatment of prostate cancer (PCa) will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs) developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse …