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Commonwealth Times 2012-01-19

Commonwealth Times, 1969-

No abstract provided.

Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz

Theses and Dissertations

Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual …

Identification And Quantification Of Protein Carbonylation By Mass Spectrometry, Qingyuan Liu

Theses and Dissertations

Accumulated evidence indicates oxidative stress plays important roles in disease and aging. Under oxidative stress, lipid peroxidation (LPO) leads to reactive carbonyl species (RCS) that can modify a wide range of biomolecules including protein, DNA and carbohydrate. In this dissertation, we investigate the modification of two model proteins, human serum albumin (HSA) and aconitase (ACO), by the LPO-relevant a, b-unsaturated aldehydes, acrolein (ACR) and 4-hydroxy-2-nonenal (HNE). The investigation is focused on the characterization and quantification ACR and HNE addition to the model proteins. A correlation between HNE modification and ACO activity is also determined. These results provide insights into the …

Dispositional Mindfulness In People Diagnosed With Cancer: The Relationship To Depressive Symptoms And Well-Being, Karen Kersting

Theses and Dissertations

Coping with a cancer diagnosis is known to be a stressful experience that can be related to declines in personal well-being and increases in distress. Dispositional mindfulness is known to be related to depressive symptoms and well-being. The primary purpose of this study was to examine the relationship between mindfulness and experiences of depressive symptoms and well-being in people recently diagnosed with cancer. Seventy-four participants who were diagnosed with cancer in the last 12 months completed an initial self-report survey, and 43 of those completed another survey 3 months later. Cross-sectional regression analysis showed that higher levels of mindfulness were …

Quantitative Genetic Methods To Dissect Heterogeneity In Complex Traits, T. Bernard Bigdeli

Theses and Dissertations

Etiological models of complex disease are elusive[46, 33, 9], as are consistently replicable findings for major genetic susceptibility loci[54, 14, 15, 24]. Commonly-cited explanations invoke low-frequency genomic variation[41], allelic heterogeneity at susceptibility loci[33, 30], variable etiological trajectories[18, 17], and epistatic effects between multiple loci; these represent among the most methodologically-challenging issues in molecular genetic studies of complex traits. The response has been con- sistently reactionary—hypotheses regarding the relative contributions of known func- tional elements, or emphasizing a greater role of rare variation[46, 33] have undergone periodic revision, driving increasingly collaborative efforts to ascertain greater numbers of participants and which assay …

Changes In Subcellular Localization Reveal Interactions Between Human Cytomegalovirus Terminase Subunits, Jian Ben Wang, Yali Zhu, Michael A. Mcvoy, Deborah S. Parris

Pediatrics Publications

No abstract provided.

An Epidemiological Study Of Anemia And Renal Dysfunction In Patients Admitted To Icus Across The United States, Donald F. Brophy, Spencer E. Harpe, Daniel E. Carl, Gretchen M. Brophy

Pharmacotherapy and Outcomes Science Publications

The aims of this study were to determine the associations between anemia of critical illness, erythropoietin stimulating agents (ESA), packed red blood cell transfusions and varying degrees of renal dysfunction with mortality, and ICU- and hospital length of stay (LOS). This was a cross-sectional retrospective study of 5,314 ICU patients from USA hospitals. Hospital, patient demographics, and clinical characteristics were collected. Predictors of mortality and hospital and ICU LOS were evaluated using multivariate logistic regression models. The mean ICU admission hemoglobin in this study was 9.4 g/dL. The prevalence of ESA use was 13% and was associated with declining renal …

Utilization Patterns Of Iv Iron And Erythropoiesis Stimulating Agents In Anemic Chronic Kidney Disease Patients: A Multihospital Study, Avani D. Joshi, David A. Holdford, Donald F. Brophy, Spencer E. Harpe, Darcy Mays, Todd W. B. Gehr

Pharmacotherapy and Outcomes Science Publications

Intravenous (IV) iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in chronic kidney disease (CKD). This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678) of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly …

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …

Resemblance Of Symptoms For Major Depression Assessed At Interview Versus From Hospital Record Review, Ying Chen, Haimin Li, Yihan Li, Dong Xie, Zhiyang Wang, Fuzhong Wang, Yuan Shen, Sulin Ni, Yan Wei, Yanhua Liu, Lanfen Liu, Chengge Gao, Jun Liu, Lijuan Yan, Gang Wang, Keqing Li, Qiang He, Tiehang Liu, Jinbei Zhang, Yan Ren, Qunli Du, Jing Tian, Honghui Chen, Yanfang Luo, Fengzhi Zhang, Guangwei Sun, Chunjie Shan, Xueyi Wang, Yutang Zhang, Xiaoqin Weng, Yunchun Chen, Zhen Kang, Jing Guan, Yiping Chen, Shenxun Shi, Kenneth S. Kendler, Jonathan Flint, Hong Deng

Psychiatry Publications

Background

Diagnostic information for psychiatric research often depends on both clinical interviews and medical records. Although discrepancies between these two sources are well known, there have been few studies into the degree and origins of inconsistencies.

Principal findings

We compared data from structured interviews and medical records on 1,970 Han Chinese women with recurrent DSM-IV major depression (MD). Correlations were high for age at onset of MD (0.93) and number of episodes (0.70), intermediate for family history (+0.62) and duration of longest episode (+0.43) and variable but generally more modest for individual depressive symptoms (mean kappa = 0.32). Four factors …

Comparison Of Statistical Tests For Association Between Rare Variants And Binary Traits, Silviu-Alin Bacanu, Matthew R. Nelson, John C. Whittaker

Psychiatry Publications

Genome-wide association studies have found thousands of common genetic variants associated with a wide variety of diseases and other complex traits. However, a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some of the missing variation is due to the effects of rare variants. Nonetheless, the statistical analysis of rare variants is challenging. A commonly used method is to contrast, within the same region (gene), the frequency of minor alleles at rare variants between cases and controls. However, this strategy is most useful under the assumption that the tested variants have …

Network-Assisted Investigation Of Combined Causal Signals From Genome-Wide Association Studies In Schizophrenia, Peilin Jia, Lily Wang, Ayman H. Fanous, Carlos N. Pato, Todd L. Edwards, Zhongming Zhao

Psychiatry Publications

With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each …

Low Dose Nicotine And Antagonism Of Β2 Subunit Containing Nicotinic Acetylcholine Receptors Have Similar Effects On Affective Behavior In Mice, Shawn M. Anderson, Darlene H. Brunzell

Pharmacology and Toxicology Publications

Nicotine leads to both activation and desensitization (inactivation) of nicotinic acetylcholine receptors (nAChRs). This study tested the hypothesis that nicotine and a selective antagonist of β2*nAChRs would have similar effects on affective behavior. Adult C57BL/6J male mice were tested in a conditioned emotional response (CER) assay which evaluates the ability of an aversive stimulus to inhibit goal-directed behavior. Mice lever-pressed for a saccharin reinforcer according to a variable schedule of reinforcement during sessions in which two presentations of a compound light/tone conditioned stimulus (CS) co-terminated with a 0.1 or 0.3 mA, 0.5 s footshock unconditioned stimulus (US). During testing in …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Pharmacology and Toxicology Publications

Aims and Hypothesis

Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

Methods

Gem-deficient mice were generated and their metabolic phenotype characterised by …

A Phase Iii Randomized Three-Arm Trial Of Physical Therapist Delivered Pain Coping Skills Training For Patients With Total Knee Arthroplasty: The Kastpain Protocol, Daniel L. Riddle, Francis J. Keefe, Dennis Ang, Khaled J., Levent Dumenci, Mark P. Jensen, Matthew J. Blair, Shelby D. Reed, Kurt Kroenke

Physical Therapy Publications

Background

Approximately 20% of patients report persistent and disabling pain following total knee arthroplasty (TKA) despite an apparently normally functioning prosthesis. One potential risk factor for unexplained persistent pain is high levels of pain catastrophizing. We designed a three-arm trial to determine if a pain coping skills training program, delivered prior to TKA, effectively reduces function-limiting pain following the procedure in patients with high levels of pain catastrophizing.

Methods/design

The trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain …

On The Specificity Of Heparin/Heparan Sulfate Binding To Proteins. Anion-Binding Sites On Antithrombin And Thrombin Are Fundamentally Different, Philip D. Mosier, Chandravel Krishnasamy, Glen E. Kellogg, Umesh R. Desai

Medicinal Chemistry Publications

Background

The antithrombin–heparin/heparan sulfate (H/HS) and thrombin–H/HS interactions are recognized as prototypic specific and non-specific glycosaminoglycan (GAG)–protein interactions, respectively. The fundamental structural basis for the origin of specificity, or lack thereof, in these interactions remains unclear. The availability of multiple co-crystal structures facilitates a structural analysis that challenges the long-held belief that the GAG binding sites in antithrombin and thrombin are essentially similar with high solvent exposure and shallow surface characteristics.

Methodology

Analyses of solvent accessibility and exposed surface areas, gyrational mobility, symmetry, cavity shape/size, conserved water molecules and crystallographic parameters were performed for 12 X-ray structures, which include 12 …

Pyridoxal 5′-Phosphate Is A Slow Tight Binding Inhibitor Of E. Coli Pyridoxal Kinase, Mohini S. Ghatge, Roberto Contestabile, Martino L. Di Salvo, Jigar V. Desai, Amit Gandhi, Christina M. Camara, Rita Florio, Isabel N. Gonzalez, Alessia Parroni, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Pyridoxal 5′-phosphate (PLP) is a cofactor for dozens of B6 requiring enzymes. PLP reacts with apo-B6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4′-aldehyde moiety forms covalent adducts with other compounds and non-B6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell …

Design, Synthesis, And In Vitro And In Vivo Biological Studies Of A 3′-Deoxythymidine Conjugate That Potentially Kills Cancer Cells Selectively, Qiong Wei, Dejun Zhang, Anna Yao, Liyi Mai, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Thymidine kinases (TKs) have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3′-Deoxythymidine phenylquinoxaline conjugate (dT-QX) was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as …

Virginia Commonwealth University Graduate And Professional Programs Bulletin [2012], Virginia Commonwealth University

VCU Bulletins

Graduate and professional programs bulletin for Virginia Commonwealth University for the academic year 2012-2013. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for graduate programs.

Intimate Partner Violence And Alcohol Problems In Interethnic And Intra-Ethnic Couples, Karen G. Chartier, Raul Caetano

Social Work Publications

Despite the growing number of interethnic marriages in the U.S., few studies have examined intimate partner violence (IPV) in interethnic couples. This article examined past-year occurrences of IPV across interethnic and intra-ethnic couples and tested correlates of IPV specifically in interethnic couples. Data were from a national survey of couples 18 years of age and older from the 48 contiguous states. Interethnic couples (n = 116) included partners from different ethnic backgrounds, including black-white, Hispanic-white, and black-Hispanic couples. White (n = 555), black (n = 358), and Hispanic (n = 527) intra-ethnic couples included partners with …

The Removal Of Pluto From The Class Of Planets And Homosexuality From The Class Of Psychiatric Disorders: A Comparison, Peter Zachar, Kenneth S. Kendler

Psychiatry Publications

We compare astronomers' removal of Pluto from the listing of planets and psychiatrists' removal of homosexuality from the listing of mental disorders. Although the political maneuverings that emerged in both controversies are less than scientifically ideal, we argue that competition for "scientific authority" among competing groups is a normal part of scientific progress. In both cases, a complicated relationship between abstract constructs and evidence made the classification problem thorny.

Evaluation Of A Revised Curriculum: A Four-Year Qualitative Study Of Student Perceptions, Sharon K. Lanning, Angela P. Wetzel, Meredith B. Baines, B. Ellen Byrne

Periodontics Publications

Following curricular revisions at the Virginia Commonwealth University School of Dentistry, this longitudinal study was designed to determine students' perceptions of their educational experience in the revised curriculum. A SWOT (Strengths, Weaknesses, Opportunities, and Threats) open-ended response questionnaire was administered to students in the class of 2011 (N=89) in January of each academic year, 2008 through 2011, followed by focus groups three months prior to graduation. The overall response rate for the questionnaire was 69 percent, and a total of fourteen students participated in four focus groups. Cumulatively, 1,382 responses (SWOT=984 and focus groups=398) were qualitatively analyzed, and five themes …

Optimizing Read Mapping To Reference Genomes To Determine Composition And Species Prevalence In Microbial Communities, John Martin, Sean Sykes, Sarah Young, Karthik Kota, Riva Sanka, Nihar U. Sheth, Joshua Orvis, Erica Sodergren, Zhengyuan Wang, George M. Weinstock, Makedonka Mitreva

Study of Biological Complexity Publications

The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners …

Geriatric Home Makeover, Edward F. Ansello

Director's Editorials from Age in Action

Houses pose substantial risks for falling. Over half of all falls by older adults happen in their homes. Reducing hazards in the home addresses just one set of contributing risk factors involved in older adults falling.

Shared Resistance To Aging And Als In Neuromuscular Junctions Of Specific Muscles, Gregorio Valdez, Juan C. Tapia, Jeff W. Lichtman, Michael A. Fox, Joshua R. Sanes

Anatomy and Neurobiology Publications

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to …

Spxa1 Involved In Hydrogen Peroxide Production, Stress Tolerance And Endocarditis Virulence In Streptococcus Sanguinis, Lei Chen, Xiuchun Ge, Xiaojing Wang, Jenishkumar R. Patel, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococcus sanguinis is one of the most common agents of infective endocarditis. Spx proteins are a group of global regulators that negatively or positively control global transcription initiation. In this study, we characterized the spxA1 gene in S. sanguinis SK36. The spxA1 null mutant displayed opaque colony morphology, reduced hydrogen peroxide (H2O2) production, and reduced antagonistic activity against Streptococcus mutans UA159 relative to the wild type strain. The ΔspxA1 mutant also demonstrated decreased tolerance to high temperature, acidic and oxidative stresses. Further analysis revealed that ΔspxA1 also exhibited a ~5-fold reduction in competitiveness in an animal model of …

Virginia Commonwealth University Fall Commencement Program [2012], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Virginia Commonwealth University Commencement Program [2012], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Augmenter Of Liver Regeneration (Alr) Promotes Liver Outgrowth During Zebrafish Hepatogenesis, Yan Li, Muhammad Farooq, Donglai Sheng, Chanchal Chandramouli, Tian Lan, Nilesh K. Mahajan, R. Manjunatha Kini, Yunhan Hong, Thomas Lisowsky, Ruowen Ge

Biochemistry and Molecular Biology Publications

Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. …