Digital Commons Network^™

Racial/Ethnic Differences In Fatality Rates From Motor Vehicle Crashes: An Analysis From A Behavioral And Cultural Perspective, Huda Hamdan

Theses and Dissertations

Ethnic/racial minorities in the United States are overrepresented in fatalities from motor vehicle crashes (MVC). Growing evidence indicates that there are differences among racial/ethnic groups in risk of involvement in fatal crashes. Based on previous research, numerous factors may be involved in high racial/ethnic fatality rates from MVCs, including failure to use safety equipment, driving while under the influence of alcohol/drug, red light running, and speeding. Using data from the Office of the Chief Medical Examiner (OCME) and the FR300P Police Crash Report, this project explores differences in variables associated with traffic safety behavior and traffic law obedience between non-White …

Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz

Theses and Dissertations

Background: Ethanol is a cardiotoxic substance that damages the heart by increasing apoptosis, free radical formation and calcium overloading. Consequently, there is an increase in cell death leaving fewer functioning myocytes leading to heart failure. Sildenafil is a phosphodiesterase type-5 (PDE-5) inhibitor approved for treatment of erectile dysfunction. Studies from our lab have demonstrated that PDE-5 inhibition reduces myocardial infarct size and attenuates post-ischemic cardiac dysfunction in both ischemia-reperfusion and permanent coronary artery ligation models. Therefore, in the present study, we hypothesized that treatment with sildenafil will prevent cardiotoxicity associated with acute alcohol exposure by reducing myocyte apoptosis and preserving …

Regulation Of Gastrointestinal Smooth Muscle Function By Hydrogen Sulfide, Ancy Nalli

Theses and Dissertations

Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, cause MLC20 dephosphorylation and muscle relaxation via inhibition of myosin light chain (MLC) kinase and activation of MLC phosphatase. Hydrogen sulfide (H2S) produced as a byproduct by luminal sulfate-reducing commensal bacteria or as an endogenous signaling molecule synthesized from L-cysteine via cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) regulates muscle contraction. However, the role of H2S in the regulation of MLC phosphatase activity and MLC20 phosphorylation is not known. The aim of the present study was to examine the expression of CSE and CBS in smooth muscle cells and to elucidate the molecular …

Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique

Theses and Dissertations

Based upon experimental evidence from the 1970’s we proposed that a reduced form of hydroxocobalamin should be capable of producing carbon dioxide (CO2) from carbon monoxide (CO) in blood, and that this conversion should be detectable. Using resonance raman spectroscopy we demonstrated that a mixture of hydroxocobalamin and ascorbic acid could create the reduced form of hydroxocobalamin. We used a closed-loop circulation system with a hollow-fiber membrane oxygenator to produce carboxyhemoglobin. Using sensitive gas monitoring equipment to the gas-out port of the oxygenator we analyzed the CO and CO2 concentrations coming from the oxygenator. The mixture of hydroxocobalamin and ascorbic …

Ink (2013-04)

Ink, 2008-

The student-run features magazine covering the fashion, art, music and culture worlds at VCU and in Richmond. Published annually in print and updated regularly online.

The Role Of Nicotinic Acetylcholine Receptors In Ethanol Responsive Behaviors And Drinking, Anton Dawson

Theses and Dissertations

The high co-morbidity between alcohol (ethanol) and nicotine abuse suggests that nicotinic acetylcholine receptors (nAChRs), which are thought to underlie nicotine dependence, may also be involved in alcohol dependence. A genomic region that encodes the Alpha5* nAChR subtype has recently been shown to be associated with alcohol dependence phenotypes in humans. Therefore, the aim of this study was to determine the role of Alpha5* nAChRs in ethanol-responsive behaviors upon acute administration in mice as well as in their drinking behavior. We conducted tests in mice lacking the Alpha5 coding gene (Chrna5) in ethanol-induced hypothermia, hypnosis, anxiolysis, and conditioned place preference. …

Rehabilitation Service Utilization Among African American Women Living With Hiv/Aids: Using The Behavioral Model For Vulnerable Populations, Aisha Shamburger-Rousseau

Theses and Dissertations

African American women represent one of the largest groups disproportionately living with and affected by HIV/AIDS yet African American women have largely been unrepresented in the federal-state rehabilitation system. As pharmaceutical treatment options improve and individuals with HIV/AIDS are living longer and healthier lives, research exploring the appropriateness of rehabilitation services has increased. Accordingly, it has become more necessary to address the needs of this population. As the largest service provider for people with disabilities, the state-federal rehabilitation system has the potential to be a vital resource for African American women living with HIV/AIDS. The purpose of this study is …

Commonwealth Times 2013-03-14

Commonwealth Times, 1969-

No abstract provided.

Commonwealth Times 2013-03-11

Commonwealth Times, 1969-

No abstract provided.

Kinetic And Thermodynamic Studies Of Thrombin Inhibitors, Aziz May Abdel

Theses and Dissertations

Sulfated low molecular weight lignins (LMWLs), CDSO3 and FDSO3, designed recently as macromolecular mimetics of heparin, were found to exhibit potent anticoagulant activity. Small molecules based on the same scaffold, SBD and SBT, showed promising thrombin inhibition. We were able to address the mechanism of the inhibition using Michaelis-Menten kinetics. All the molecules were found to be allosterically impairing thrombin activity using either noncompetitive or uncompetitive mechanism. Absence of competition with hirugen, an exosite 1 ligand, and competition with polymeric heparin points to exosite 2 as the site of interaction for these inhibitors. Yet mixed competition results with other exosite …

Antisocial Behavior From Adolescence To Early Adulthood: Heritability, Stability, And Correlates Using A Longitudinal Twin Sample, Ashley Dibble

Theses and Dissertations

The purpose of this study was to examine the heritability, stability, and outcomes of antisocial behavior from adolescence into adulthood in a longitudinal twin sample. Specifically, the genetic and environmental influences on conduct disorder, adult antisocial behavior, and alcohol dependence were examined. The influence of genes and environment on the relationship between these disorders was also examined. The study utilized a subset of FinnTwin12, a population-based twin study that consists of five consecutive birth cohorts. The subsample consisted of 1035 twin pairs (N = 2070) and of that 2070, 1854 completed the intensive interview at age 14. At age 22, …

Positive Allosteric Modulators Of Alpha4beta2 Neuronal Nicotinic Receptors: Synthesis And In Vitro Studies, Atul Jain

Theses and Dissertations

des-Formylflustrabromine (dFBr), isolated from the marine organism Flustra foliacea, is the first selective, positive allosteric modulator (PAM) of α4β2 nicotinic acetylcholine receptors that potentiates the action of the neurotransmitter acetylcholine (ACh). Most agonists for this receptor population are not selective and can activate other nACh receptors. A selective PAM, which activates α4β2 nACh receptors only in the presence of ACh, might find application in the treatment of of various neurological diseases such as Alzheimer’s disease or autism. dFBr was examined and found to produce a biphasic dose-response curve over a wide concentration range (i.e., potentiation at low concentration, but inhibition …

Klf2 Is Required For Normal Mouse Cardiovascular Development, Aditi Raghunath Chiplunkar

Theses and Dissertations

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Ethanol Regulation Of Serum Glucocorticoid Kinase 1 Expression In Dba2/J Mouse Prefrontal Cortex, Blair N. Costin, Seth M. Dever, Michael F. Miles

Pharmacology and Toxicology Publications

Background

We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions …

Cannabinoid Cb2 Receptors Regulate Central Sensitization And Pain Responses Associated With Osteoarthritis Of The Knee Joint, James J. Burston, David R. Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A. Walsh, David A. Kendall, Aron H. Lichtman, Victoria Chapman

Pharmacology and Toxicology Publications

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that …

A Core Microbiome Associated With The Peritoneal Tumors Of Pseudomyxoma Peritonei, Jeremy J. Gilreath, Cristina Semino-Mora, Christopher J. Friedline, Hui Liu, Kip L. Bodi, Thomas J. Mcavoy, Jennifer Francis, Carol Nieroda, Armando Sardi, Andre Dubois, David W. Lazinski, Andrew Camilli, Traci L. Testerman, D Scott Merrell

Study of Biological Complexity Publications

Background

Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease.

Methods

To more clearly define the …

Endosymbiosis In Trypanosomatids: The Genomic Cooperation Between Bacterium And Host In The Synthesis Of Essential Amino Acids Is Heavily Influenced By Multiple Horizontal Gene Transfers, João M.P. Alves, Cecilia C. Klein, Flávia Maia Da Silva, André G. Costa-Martins, Myrna G. Serrano, Gregory A. Buck, Ana Tereza R. Vasconcelos, Marie-France Sagot, Marta M.G. Teixeira, Maria Cristina M. Motta, Erney P. Camargo

Study of Biological Complexity Publications

Background

Trypanosomatids of the genera Angomonas and Strigomonas live in a mutualistic association characterized by extensive metabolic cooperation with obligate endosymbiotic Betaproteobacteria. However, the role played by the symbiont has been more guessed by indirect means than evidenced. Symbiont-harboring trypanosomatids, in contrast to their counterparts lacking symbionts, exhibit lower nutritional requirements and are autotrophic for essential amino acids. To evidence the symbiont’s contributions to this autotrophy, entire genomes of symbionts and trypanosomatids with and without symbionts were sequenced here.

Results

Analyses of the essential amino acid pathways revealed that most biosynthetic routes are in the symbiont genome. By contrast, the …

Global Taxonomic Diversity Of Living Reptiles, Daniel Pincheira-Donoso, Aaron M. Bauer, Shai Meiri, Peter Uetz

Study of Biological Complexity Publications

Reptiles are one of the most ecologically and evolutionarily remarkable groups of living organisms, having successfully colonized most of the planet, including the oceans and some of the harshest and more environmentally unstable ecosystems on earth. Here, based on a complete dataset of all the world’s diversity of living reptiles, we analyse lineage taxonomic richness both within and among clades, at different levels of the phylogenetic hierarchy. We also analyse the historical tendencies in the descriptions of new reptile species from Linnaeus to March 2012. Although (non-avian) reptiles are the second most species-rich group of amniotes after birds, most of …

Contributions Of Vldlr And Lrp8 In The Establishment Of Retinogeniculate Projections, Jianmin Su, Michael A. Klemm, Anne M. Josephson, Michael A. Fox

Anatomy and Neurobiology Publications

Background

Retinal ganglion cells (RGCs), the output neurons of the retina, project to over 20 distinct brain nuclei, including the lateral geniculate nucleus (LGN), a thalamic region comprised of three functionally distinct subnuclei: the ventral LGN (vLGN), the dorsal LGN (dLGN) and the intergeniculate leaflet (IGL). We previously identified reelin, an extracellular glycoprotein, as a critical factor that directs class-specific targeting of these subnuclei. Reelin is known to bind to two receptors: very-low-density lipoprotein receptor (VLDLR) and low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2). Here we examined the roles of these canonical reelin …

Paclitaxel-Induced Apoptosis Is Bak-Dependent, But Bax And Bim-Independent In Breast Tumor, Anna V. Miller, Mark A. Hicks, Wataru Nakajima, Amanda C. Richardson, Jolene J. Windle, Hisashi Harada

Philips Institute for Oral Health Research Publications

Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim−/− MEFs (mouse embryonic fibroblasts), the bim−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel …

Two-Component System Response Regulators Involved In Virulence Of Streptococcus Pneumoniae Tigr4 In Infective Endocarditis, My Trihn, Xiuchun Ge, Alleson Dobson, Todd Kitten, Cindy Munro, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococci resident in the oral cavity have been linked to infective endocarditis (IE). While other viridans streptococci are commonly studied in relation to IE, less research has been focused on Streptococcus pneumoniae. We established for the first time an animal model of S. pneumoniae IE, and examined the virulence of the TIGR4 strain in this model. We hypothesized that two-component systems (TCS) may mediate S. pneumoniae TIGR4 strain virulence in IE and examined TCS response regulator (RR) mutants of TIGR4 in vivo with the IE model. Thirteen of the 14 RR protein genes were mutagenized, excluding only the essential …

The Geometry Of Locomotive Behavioral States In C. Elegans, Thomas Gallagher, Theresa Bjorness, Robert Greene, Young-Jai You, Leon Avery

Biochemistry and Molecular Biology Publications

We develop a new hidden Markov model-based method to analyze C elegans locomotive behavior and use this method to quantitatively characterize behavioral states. In agreement with previous work, we find states corresponding to roaming, dwelling, and quiescence. However, we also find evidence for a continuum of intermediate states. We suggest that roaming, dwelling, and quiescence may best be thought of as extremes which, mixed in any proportion, define the locomotive repertoire of C elegans foraging and feeding behavior.

Light-Induced Translocation Of Rgs9-1 And Gβ5l In Mouse Rod Photoreceptors, Mei Tian, Marisa Zallocchi, Weimin Wang, Ching-Kang Chen, Krzysztof Palczewski, Duane Delimont, Dominic Cosgrove, You-Wei Peng

Biochemistry and Molecular Biology Publications

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S475 to a significant degree. Dim light exposure leads to quick de-phosphorylation of …

Hif- And Non-Hif-Regulated Hypoxic Responses Require The Estrogen-Related Receptor In Drosophila Melanogaster, Yan Li, Divya Padmanabha, Luciana B. Gentile, Catherine I. Dumur, Robert B. Beckstead, Keith D. Baker

Biochemistry and Molecular Biology Publications

Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. …

Hypothermic Machine Perfusion Preservation Of The Dcd Kidney: Machine Effects, Susanne L. Lindell, Heather Muir, John Brassil, Martin J. Mangino

Surgery Publications

Purpose. Kidneys from DCD donors represent a significant pool, but preservation problems exist. The study objective was to test the importance of machine type for hypothermic preservation of DCD kidneys.Methods. Adult Beagle dog kidneys underwent 45 minutes of warm in situ ischemia followed by hypothermic perfusion for 24 hours (Belzer-MPS Solution) on either an ORS LifePort or a Waters RM3 using standard perfusion protocols. Kidneys were then autotransplanted, and renal function was assessed over 7 days following contralateral nephrectomy. Results. Renal vascular resistance was not different between the two pumps. After 24 hours, the oxygen partial pressure and oxygen delivery …

Htert Promoter Polymorphism, -1327c>T, Is Associated With The Risk Of Epithelial Cancer, Toshihiko Iizuka, Motoji Sawabe, Kaiyo Takubo, Miao Liu, Yukio Homma, Motofumi Suzuki, Tomio Arai

Internal Medicine Publications

Telomeres are repetitive nucleotide sequences that cap the end of eukaryotic chromosomes. Attrition of these structures has been associated with carcinogenesis in many tissues, and therefore, they are essential for chromosome stabilization. Telomeres are maintained by telomerase complexes, of which human telomerase reverse transcriptase (hTERT) is an essential component. A functional polymorphism, -1327C>T (rs2735940), located in the promoter of the hTERT gene is associated with telomere length in peripheral blood leukocytes. We hypothesized that this polymorphism might affect susceptibility to various epithelial malignancies. The -1327C>T polymorphism was examined in 1,551 consecutive autopsy cases (mean age, 80.3 years), and …

Fenretinide Causes Emphysema, Which Is Prevented By Sphingosine 1-Phoshate, Masanori Yasuo, Shiro Mizuno, Jeremy Allegood, Donatas Kraskauskas, Harm J. Bogaard, Sarah Spiegel, Norbert F. Voelkel

Internal Medicine Publications

Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive …

Modulation Of The Metabiome By Rifaximin In Patients With Cirrhosis And Minimal Hepatic Encephalopathy, Jasmohan S. Bajaj, Douglas M. Heuman, Arun J. Sanyal, Phillip B. Hylemon, Richard K. Sterling, R. Todd Stravitz, Michael Fuchs, Jason M. Ridlon, Kalyani Daita, Pamela Monteith, Nicole A. Noble, Melanie B. White, Andmorgan Fisher, Masoumeh Sikaroodi, Huzefa Rangwala, Patrick M. Gillevet

Internal Medicine Publications

Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE.

Methods

Twenty cirrhotics with MHE …

Development, Disease, And Regeneration Of Tissues In The Dental-Craniofacial Complex, Brian L. Foster, Yong-Hee P. Chun, Erica L. Scheller, Zhao Lin, Chad M. Novince, Avina Paranjpe

Periodontics Publications

This article has no abstract.

An Entropy-Based Automated Cell Nuclei Segmentation And Quantification: Application In Analysis Of Wound Healing Process, Varun Oswal, Ashwin Belle, Robert Diegelmann, Kayvan Najarian

Computer Science Publications

The segmentation and quantification of cell nuclei are two very significant tasks in the analysis of histological images. Accurate results of cell nuclei segmentation are often adapted to a variety of applications such as the detection of cancerous cell nuclei and the observation of overlapping cellular events occurring during wound healing process in the human body. In this paper, an automated entropy-based thresholding system for segmentation and quantification of cell nuclei from histologically stained images has been presented. The proposed translational computation system aims to integrate clinical insight and computational analysis by identifying and segmenting objects of interest within histological …