Digital Commons Network^™

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 …

A Statistical Method For Excluding Non-Variable Cpg Sites In High-Throughput Dna Methylation Profiling, Hailong Meng, Andrew R. Joyce, Daniel E. Adkins, Yankai Jia, Guoya Li, Tapas K. Sengupta, Barbara K. Zedler, E, Lenn Murrelle, Edwin Jcg Van Den Oord

Biomarker Research and Personalized Medicine Publications

Background

High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers.

Results

We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites …

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 …

Analysis Of The Consistency Of A Mixed Integer Programming-Based Multi-Category Constrained Discriminant Model, J. Paul Brooks, Eva K. Lee

Statistical Sciences and Operations Research Publications

Classification is concerned with the development of rules for the allocation of observations to groups, and is a fundamental problem in machine learning. Much of previous work on classification models investigates two-group discrimination. Multi-category classification is less-often considered due to the tendency of generalizations of two-group models to produce misclassification rates that are higher than desirable. Indeed, producing “good” two-group classification rules is a challenging task for some applications, and producing good multi-category rules is generally more difficult. Additionally, even when the “optimal” classification rule is known, inter-group misclassification rates may be higher than tolerable for a given classification model. …

Chemotherapy In Conjoint Aging-Tumor Systems: Some Simple Models For Addressing Coupled Aging-Cancer Dynamics, Mitra S. Feizabadi, Tarynn M. Witten

Study of Biological Complexity Publications

Background

In this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts) is considered as logistic only.

Results

We demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can …

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 …

Virginia Commonwealth University Commencement Program [2010], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

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 …

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 …

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 …

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.

Toward Engineering Synthetic Microbial Metabolism, George Howard Mcarthur Iv, Stephen S. Fong

Chemical and Life Science Engineering Publications

The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel function. Further development of analytical and computer-aided design tools should accelerate the forward engineering of precisely regulated synthetic pathways by providing a standard framework for the predictable design of biological systems from well-characterized parts. In this review we discuss the current state of synthetic biology within a four-stage framework (design, modeling, …

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 …

Epsvr And Epmeta: Prediction Of Antigenic Epitopes Using Support Vector Regression And Multiple Server Results, Shide Liang, Dandan Zheng, Daron M. Standley, Bo Yao, Martin Zacharias, Chi Zhang

Radiation Oncology Publications

Background Accurate prediction of antigenic epitopes is important for immunologic research and medical applications, but it is still an open problem in bioinformatics. The case for discontinuous epitopes is even worse - currently there are only a few discontinuous epitope prediction servers available, though discontinuous peptides constitute the majority of all B-cell antigenic epitopes. The small number of structures for antigen-antibody complexes limits the development of reliable discontinuous epitope prediction methods and an unbiased benchmark to evaluate developed methods.

Results In this work, we present two novel server applications for discontinuous epitope prediction: EPSVR and EPMeta, where EPMeta is a …

Dynamic Dependence On Atr And Atm For Double-Strand Break Repair In Human Embryonic Stem Cells And Neural Descendants, Bret R. Adams, Sarah E. Golding, Raj R. Rao, Kristoffer Valerie

Radiation Oncology Publications

The DNA double-strand break (DSB) is the most toxic form of DNA damage. Studies aimed at characterizing DNA repair during development suggest that homologous recombination repair (HRR) is more critical in pluripotent cells compared to differentiated somatic cells in which nonhomologous end joining (NHEJ) is dominant. We have characterized the DNA damage response (DDR) and quality of DNA double-strand break (DSB) repair in human embryonic stem cells (hESCs), and in vitro-derived neural cells. Resolution of ionizing radiation-induced foci (IRIF) was used as a surrogate for DSB repair. The resolution of γ-H2AX foci occurred at a slower rate in hESCs …

Virginia Commonwealth University Fall Commencement Program [2010], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Virginia Commonwealth University Graduate And Professional Programs Bulletin Courses [2010], Virginia Commonwealth University

VCU Bulletins

Listing of professional and graduate courses for 2010-2011.

Virginia Commonwealth University Undergraduate Bulletin [2010], Virginia Commonwealth University

VCU Bulletins

Undergraduate bulletin for Virginia Commonwealth University for the academic year 2010-2011. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for undergraduate programs.

Genetic Basis Of Growth Adaptation Of Escherichia Coli After Deletion Of Pgi, A Major Metabolic Gene, Pep Charusanti, Tom M. Conrad, Eric M. Knight, Karthik Venkataraman, Nicole L. Fong, Bin Xie, Yuan Gao, Bemhard O. Palsson

Study of Biological Complexity Publications

Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi) by adaptively evolving ten replicates of E. coli lackingpgi for 50 days in glucose M9 minimal medium and …

Here, There, And Everywhere: A Review Of Diy U By Anya Kamenetz, Jonathan D. Becker

Educational Leadership Publications

Book Review of DIY U: Edupunks, Edupreneurs, and the Coming Transformation of Higher Education by Anya Kamenetz.

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 …

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 …

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 …

A Systems Biology Approach To Invasive Behavior: Comparing Cancer Metastasis And Suburban Sprawl Development, John J. Ryan, Benjamin L. Dows, Michael V. Kirk, Xueming Chen, Jeffrey R. Eastman, Rodney J. Dyer, Lemont B. Kier

Biology Publications

Background

Despite constant progress, cancer remains the second leading cause of death in the United States. The ability of tumors to metastasize is central to this dilemma, as many studies demonstrate successful treatment correlating to diagnosis prior to cancer spread. Hence a better understanding of cancer invasiveness and metastasis could provide critical insight.

Presentation of the hypothesis

We hypothesize that a systems biology-based comparison of cancer invasiveness and suburban sprawl will reveal similarities that are instructive.

Testing the hypothesis

We compare the structure and behavior of invasive cancer to suburban sprawl development. While these two systems differ vastly in dimension, …

Nuclear Gene Phylogeography Using Phase: Dealing With Unresolved Genotypes, Lost Alleles, And Systematic Bias In Parameter Estimation, Ryan C. Garrick, Paul Sunnucks, Rodney J. Dyer

Biology Publications

Background

A widely-used approach for screening nuclear DNA markers is to obtain sequence data and use bioinformatic algorithms to estimate which two alleles are present in heterozygous individuals. It is common practice to omit unresolved genotypes from downstream analyses, but the implications of this have not been investigated. We evaluated the haplotype reconstruction method implemented by PHASE in the context of phylogeographic applications. Empirical sequence datasets from five non-coding nuclear loci with gametic phase ascribed by molecular approaches were coupled with simulated datasets to investigate three key issues: (1) haplotype reconstruction error rates and the nature of inference errors, (2) …

Virginia Dental Journal (Vol. 87, No. 3, 2010)

Virginia Dental Journal

No abstract provided.

Interactions Between Competition And Predation Shape Early Growth And Survival Of Two Neotropical Hylid Tadpoles [Poster], Sergio C. Gonzalez, Justin C. Touchon, James R. Vonesh

Biology Presentations

Background/Question/Methods

Recent literature reviews reveal that competition typically has stronger effects on growth than the presence of predators, while predation has larger effects on survival. Further, past studies show that predators typically lessen the negative effect of competition on growth and also make interspecific competition beneficial for the survival of focal species. We examine the independent and combined effects of competition and predation for survival and growth of the tadpoles of two co-occurring Neotropical hylid frogs (Agalychnis callidryas and Dendropsophus ebraccatus). Our experiment crossed tadpole species composition (single and mixed at single total density) with the presence or absence of …

Terrestrial Predators And Abiotic Conditions Affect Hatching Survival Of Arboreal Frog Eggs: Implications For Aquatic Food Web Dynamics [Poster], Jessica Hite, James R. Vonesh

Biology Presentations

Background/Question/Methods
Recent work in food web studies has highlighted the importance of terrestrial and aquatic linkages and the trait and density-mediated effects of predators and abiotic conditions. Many studies have focused on species with complex life histories (amphibians and aquatic insects) because they encompass a variety of trophic levels and form important linkages between terrestrial and aquatic food webs. For example, red-eyed treefrog, Agalychnis callidryas eggs are deposited on vegetation overhanging ponds and risk mortality from a variety of terrestrial predators and abiotic stressors. Red-eyed treefrog embryos, however, exhibit phenotypic plasticity in hatching time in response to these terrestrial stressors. …