Digital Commons Network^™

Evaluation Of Association Tests For Rare Variants Using Simulated Data Sets In The Genetic Analysis Workshop 17 Data, Wenan Chen, Xi Gao, Jiexun Want, Chuanyu Sun, Wen Wan, Degui Zhi, Nianjun Liu, Xiangning Chen, Guimin Gao

Biostatistics Publications

We evaluate four association tests for rare variants—the combined multivariate and collapsing (CMC) method, two weighted-sum methods, and a variable threshold method—by applying them to the simulated data sets of unrelated individuals in the Genetic Analysis Workshop 17 (GAW17) data. The family-wise error rate (FWER) and average power are used as criteria for evaluation. Our results show that when all nonsynonymous SNPs (rare variants and common variants) in a gene are jointly analyzed, the CMC method fails to control the FWER; when only rare variants (single-nucleotide polymorphisms with minor allele frequency less than 0.05) are analyzed, all four methods can …

Virginia Dental Journal (Vol. 88, No. 1, 2011)

Virginia Dental Journal

No abstract provided.

3d Mapping Of The Spry2 Domain Of Ryanodine Receptor 1 By Single-Particle Cryo-Em, Alex Peralvaerz-Marin, Hanshen Tae, Phillip G. Board, Marco G. Casarotto, Angela F. Dulhunty, Montserrat Samsó

Physiology and Biophysics Publications and Presentations

The type 1 skeletal muscle ryanodine receptor (RyR1) is principally responsible for Ca2+release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208) in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the …

Cholesterol Sensitivity Of Kir2.1 Is Controlled By A Belt Of Residues Around The Cytosolic Pore, Avia Rosenhouse-Dantsker, Diomedes E. Logothetis, Irena Levitan

Physiology and Biophysics Publications and Presentations

Abstract

Kir channels play an important role in setting the resting membrane potential and modulating membrane excitability. A common feature of several Kir channels is that they are regulated by cholesterol. Yet, the mechanism by which cholesterol affects channel function is unclear. We recently showed that the cholesterol sensitivity of Kir2 channels depends on several CD-loop residues. Here we show that this cytosolic loop is part of a regulatory site that also includes residues in the G-loop, the N-terminus, and the connecting segment between the C-terminus and the inner transmembrane helix. Together, these residues form a cytosolic belt that surrounds …

State-Dependent Camp Binding To Functioning Hcn Channels Studied By Patch-Clamp Fluorometry, Shengjun Wu, Zhanna V. Vysotskaya, Xinping Xu, Changan Xie, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications and Presentations

Abstract

One major goal of ion channel research is to delineate the molecular events from the detection of the stimuli to the movement of channel gates. For ligand-gated channels, it is challenging to separate ligand binding from channel gating. Here we studied the cyclic adenosine monophosphate (cAMP)-dependent gating in hyperpolarization-activated cAMP-regulated (HCN) channel by simultaneously recording channel opening and ligand binding, using the patch-clamp fluorometry technique with a unique fluorescent cAMP analog that fluoresces strongly in the hydrophobic binding pocket and exerts regulatory effects on HCN channels similar to those imposed by cAMP. Corresponding to voltage-dependent channel activation, we observed …

"We Are Joined Together Temporarily" The Tragic Mulatto, Fusion Monster In Lee Frost's The Thing With Two Heads, Justin Ponder

Ethnic Studies Review

In Lee Frost's 1972 film The Thing with Two Heads, a white bigot unknowingly has his head surgically grafted onto the body of a black man. From that moment on, these two personalities compete for control of their shared body with ridiculous results. Somewhere between horror and comedy, this Blaxploitation film occupies a strange place in interracial discourse. Throughout American literature, the subgenre of tragic mulatto fiction has critiqued segregation by focusing on the melodramatic lives of those divided by the color line. Most tragic mulatto scholarship has analyzed overtly political novels written by African American writers from the Reconstruction …

Characterization Of The Expression Of Bdnf And Cgrp And Their Regulatory Pathways In Dorsal Root Ganglion During Cystitis., Sharon Yu

Theses and Dissertations

Interstitial cystitis is a chronic debilitating disease that causes pain and increased frequency of micturition, amongst other symptoms, without any identifiable cause. This disease affects a large number of the population, yet the etiology is still unknown. The present study aimed to characterize BDNF and CGRP—two neuropeptides that have both been proven to play an important role in the transmission of pain as well as in hypersensitivity. The signaling pathways regulating the expression of the two neuropeptides were also examined. Results revealed that BDNF protein expression levels increased in both L1 and L6 DRG following 48 hours post CYP-induced cystitis. …

Systematic Study Of Gene Functions For Morphological Chain Formation In Streptococcus Sanguinis, Karra Evans

Theses and Dissertations

Streptococcus sanguinis is a gram-positive facultative anaerobe that is indigenous to the oral cavity and a primary colonizer of the oral cavity. It serves as a tether for the attachment of several oral bacteria that colonize the tooth surface, form dental plaque, and cause periodontal disease. Previous experiments with streptococcal strains have suggested that cellular chain morphology of streptococci may influence the competitiveness, susceptibility to phagocytosis, acidurance, and aggregation of the bacterium. The purpose of this study was to systematically determine gene functions that contribute to cellular chain length morphology in the SK36 strain of S. sanguinis. Gene functions for …

Identity And The Legislative Decision Making Process: A Case Study Of The Maryland State Legislature, Nadia Brown

Ethnic Studies Review

Both politicians and the mass public believe that identity influences political behavior yet, political scientists have failed to fully detail how identity is salient for all political actors not just minorities and women legislators. To what extent do racial, gendered, and race/gendered identities affect the legislation decision process? To test this proposition, I examine how race and gender based identities shape the legislative decisions of Black women in comparison to White men, White women, and Black men. I find that Black men and women legislators interviewed believe that racial identity is relevant in their decision making processes, while White men …

Annual Higher Ground Women's Leadership Conference 2011, The Grace E. Harris Leadership Institute At Virginia Commonwealth University

GEHLI - 2026 VCUL Team Project Publications

No abstract provided.

The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker

Theses and Dissertations

Periodontitis affects 10 to 15 percent of most adult populations and can contribute to numerous systemic diseases. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized prime causative agent in periodontitis. Studies have shown a number of small non-coding RNAs (sRNAs) have been related to bacterial virulence. Many of these sRNAs require the facilitation of the bacterial Sm-like protein, Hfq, for optimum function. Hfq is a RNA chaperone involved in RNA stability, sRNA function, and polyadenylation. Mutants lacking in Hfq often show pleiotropic phenotypes, although the extent and severity of hfq null phenotypes is often species-specific. Hfq has been encoded …

Synthesis, Screening And Cocrystallization Of Adenosine Based Inhibitors With Methyltransferases, Ermc' And Ksga, Matthew Baker

Theses and Dissertations

Antibiotic resistance threatens to throw mankind back into an era when infectious disease was the predominant cause of death. In an effort to mitigate this danger, we targeted ErmC’ and KsgA. Both methylate N6-adenosine of ribosomal RNA, though each serve different roles in their bacterial host. ErmC’ dimethylates A2058 on 23S rRNA, conferring resistance to MLSB antibiotics (macrolides, lincosamides, streptogramin B). KsgA aids in ribosome assembly, binding inactive 30S until dimethylating A1518/A1519 of 16S rRNA. Like most methyltransferases, ErmC’ and KsgA use cofactor S-adenosylmethionine (SAM) as their methyl source, which binds adjacent to their specific adenosine substrate. ErmC’ inhibitors could …

Investigating The Relationship Between Governance Mechanisms And The Disclosure Of It Control Weaknesses, Basil Hamdan

Theses and Dissertations

The current research is concerned with exploring the quality of information technology (IT) control over financial reporting systems as reported under Section 404 of the Sarbanes-Oxley Act of 2002. More specifically, this dissertation examines the association between organizational governance mechanisms and the occurrence and subsequent disclosure of IT control weaknesses. Despite the adverse impact of IT control weaknesses on internal control quality and financial reporting reliability, research on IT controls in general and IT control weaknesses in particular remains largely anecdotal with limited reliance on theory. The current work proposes and tests an integrated theoretical model of the antecedents of …

Virginia Dental Journal (Vol. 88, No. 2, 2011)

Virginia Dental Journal

No abstract provided.

Virginia Dental Journal (Vol. 88, No. 3, 2011)

Virginia Dental Journal

No abstract provided.

Virginia Dental Journal (Vol. 88, No. 4, 2011)

Virginia Dental Journal

No abstract provided.

Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore

Theses and Dissertations

Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …

Making Waves: Library It As A Disruptive Force, Erin White, Thomas Mcnulty

VCU Libraries Faculty and Staff Presentations

This presentation addresses special challenges and opportunities that Library IT departments face as they take a larger role in initiating change within an organization.

A Study On The Effects Of Therapeutic Listening On The Social And Functional Behavior Of Preschool Children With Autism Spectrum Disorder, Robin Abbott

Theses and Dissertations

Auditory sensory differences and sensitivities are often mentioned by parents of children with Autism Spectrum Disorder (ASD), and in research involving children with ASD. Addressing these auditory processing differences is the goal of various auditory treatment techniques, but current research does not yield a body of evidence in support of auditory therapy as a treatment for children with ASD. This study is a single-subject study, repeated across two subjects, to investigate the effect of the Therapeutic Listening program on the social engagement and self-care skills of preschool-aged children with ASD. Both social engagement and self-care skills increased with for both …

Evolution Of Physical Therapy At The Medical College Of Virginia And Virginia Commonwealth University, Mary Snyder Shall

VCU University History Books

The Physical Therapy Department at Virginia Commonwealth University was founded in 1931 as part of the College of William and Mary’s Richmond division, becoming Virginia’s first program in the field of physical therapy. Through archived files, yearbooks and interviews with faculty and alumni, this book describes important events of the department’s first 80 years and highlights the faculty members and alumni who influenced the local and national development of the profession.

Playing With Aesthetics In Art Museums, Susan Glasser

Theses and Dissertations

"Playing with Aesthetics in Art Museums" presents a strategy for using design thinking to mediate engrossing art experiences for adult museum visitors. Built upon a substantiated family resemblance between art and play experiences, the study synthesizes a typology of aesthetic theories, ten germane tenets of game design, and a psychographic portrait of the "archetypal" museum visitor to create a practical framework for delivering engrossing art experiences to adult visitors who typically enter museums with limited art historical knowledge. The interdisciplinary approach used is intended to replace the singular methodologies (whether art historical, pedagogical or aesthetic) that have informed museum practice …

A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller

Theses and Dissertations

Exposure to environmental tobacco smoke (ETS) has been recognized as a significant health risk for adults and children. In adults, ETS exposure has been linked to increased incidences of cardiovascular disease and dementia. In children, exposure has been linked to behavioral and cognitive deficits. Studies on the effects of ETS in the brain have been largely epidemiological, and have lacked a defined explanation of the molecular/biochemical effects of ETS. The present dissertation aims to test whether ETS exposure leads to altered biochemistry in the adult and developing mammalian brain. A rat ETS exposure model was employed to investigate changes at …

Cyclic-Di-Gmp Signaling In The Borrelia Spirochetes, John Freedman

Theses and Dissertations

Lyme disease is the most common tick-borne disease in North America, with approximately 35,000 cases reported to the Centers for Disease Control in 2008. The genome of its causative agent, Borrelia burgdorferi, encodes for a set of genes involved in the metabolism and regulatory activities of the second messenger nucleotide, cyclic-di-GMP (c-di-GMP). Rrp1 is a response regulatory-diguanylate cyclase, and its regulatory capability is likely mediated via production of c-di-GMP, as it lacks a DNA-binding domain. One known class of c-di-GMP effector/binding proteins are those that harbor a PIlZ domain. The genome of B. burgdorferi strain 5A4 encodes for one chromosomally-carried …

Genetic Manipulation Of The Relapsing Fever Spirochete Borrelia Hermsii Permits Novel Investigation Into The Role Of Factor H Binding In Borrelial Virulence, Lindy Fine

Theses and Dissertations

Borrelia hermsii, an etiologic agent of tick-borne relapsing fever, binds negative complement regulator factor H (FH) via its FhbA protein. Direct demonstration of the role of FhbA in the disease process has been hindered by the lack of genetic manipulation systems for the relapsing fever Borrelia. Here, we demonstrate successful generation of a B. hermsii strain YOR fhbA deletion mutant (Bh YORΔfhbA) that constitutively produces green fluorescent protein (GFP). Genetic manipulation did not affect growth rate or plasmid composition. Bh YORΔfhbA lost factor H-binding and C3b-inactivation capabilities, but retained resistance to killing in human serum and infectivity in mice. Stable …

The Cultural Context Of Alzheimer’S Disease: The Impact Of Perception And Knowledge On Willingness To Seek Medcial [I.E., Medical] Help Among Ghanaian Immigrants In The United States., Olivia Owusu-Boakyewaah

Theses and Dissertations

This correlational study explored the knowledge, perceived seriousness, and willingness to seek medical help for Alzheimer’s Disease (AD) among Ghanaian Immigrants currently residing in the Unites States. Study participants were 163 Ghanaian Immigrants between the ages of 45 and 90, attending Ghanaian community churches in Virginia and Maryland. Significant results include a positive correlation between knowledge and perceived seriousness of the disease, perceived seriousness of the disease was negatively correlated with caregiving experience. These results as well as several seemingly counterintuitive findings are discussed in terms of the Health Disparities and Psychometric challenges. Specifically, these results points to the necessity …

Acquired Cytogenetic Changes In Adult Twins Discordant For A History Of Childhood Sexual Abuse, Jenni Brumelle

Theses and Dissertations

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) …

African American Males Diagnosed With Schizophrenia: A Phenomenological Study, Lorraine Anderson

Theses and Dissertations

Abstract Little is known about how African American men with schizophrenia experience their every day existence. Through applying interpretive phenomenology and using a methodological structure designed by van Manen (1990, 1997), this research aimed to enrich the understanding of living with schizophrenia for these African American males. In this study, five men ranging in age from 21 to 57 described their lives within the context of existing with the diagnosis of schizophrenia. The lived experiences across the interviews revealed four overarching themes: They know that they are mentally ill; they make a special effort to test reality; they assert their …

Head-Start Juvenile And Adult Resident Eastern Box Turtles (Terrapene Carolina Carolina): Winter Ecology Including Microhabitat Selection, Temperature Tolerance And Philopatry, Amberly Moon

Theses and Dissertations

The Eastern box turtle (Terrapene carolina carolina) is one of the most common reptiles in North America, but is soon to be threatened due to increased urbanization, disease, and the pet and food trades. In order to assist resource managers in choosing suitable sites for relocation studies, more information on the winter ecology of this species is necessary. We examined the temperature tolerance, microhabitat and degree of philopatry to hibernacula for juvenile and adult E. box turtles for two consecutive winters in Charles City Co, VA. The turtles were tracked via radio telemetry to record point locations during the active …

Hindfoot And Forefoot Kinematic Differences Among Individuals With And Without Functional Ankle Instability, Cynthia Wright

Theses and Dissertations

Introduction: Following lateral ankle sprain, many individuals experience recurrent injury and symptoms of giving-way, known as Functional Ankle Instability (FAI). It has been proposed that altered joint kinematics during activity may contribute to instability in these individuals, however research findings have been inconsistent. Objective: To capture foot and ankle kinematic data during two common tasks (walking gait and jump landing) among three groups: individuals with FAI, healthy controls and copers. Design: 3-group observational cross-sectional study. Participants: Participants included 23 individuals with a history of ≥ 1 ankle sprain and at least 2 episodes of giving-way in the past year (FAI: …

Biochemical Evaluation Of Lignin-Like Molecules, Jay Thakkar

Theses and Dissertations

Current anticoagulants carry a serious risk of bleeding complications. In addition, narrow therapeutic index, drug interactions, immunological reactions, toxicity and high cost to benefit ratio limits the effective use of these drugs in patients with thrombotic conditions.Heparin is the most widely used anticoagulant. We hypothesized that one of the major drawback of heparins, its non-specific interaction with the plasma proteins arises as a result of negative charges. To reduce these non-specific interactions, our laboratory designed sulfated low molecular weight lignin (LMWL) like biomacromolecules, which were found to be direct inhibitors of thrombin and factor Xa, acting through a unique exosite-2 …