Digital Commons Network^™

Reduction Of The Hiv Protease Inhibitor-Induced Er Stress And Inflammatory Response By Raltegravir In Macrophages, Xiaoxuan Zhang, Risheng Cao, Ruping Liu, Renping Zhao, Yi Huang, Emily C. Gurley, Phillip B. Hylemon, William M. Pandak, Guangji Wang, Luyong Zhang, Xiaokun Li, Huiping Zhou

Microbiology and Immunology Publications

Background

HIV protease inhibitor (PI), the core component of highly active antiretroviral treatment (HAART) for HIV infection, has been implicated in HAART-associated cardiovascular complications. Our previous studies have demonstrated that activation of endoplasmic reticulum (ER) stress is linked to HIV PI-induced inflammation and foam cell formation in macrophages. Raltegravir is a first-in-its-class HIV integrase inhibitor, the newest class of anti-HIV agents. We have recently reported that raltegravir has less hepatic toxicity and could prevent HIV PI-induced dysregulation of hepatic lipid metabolism by inhibiting ER stress. However, little information is available as to whether raltegravir would also prevent HIV PI-induced inflammatory …

Antigen Transfer From Exosomes To Dendritic Cells As An Explanation For The Immune Enhancement Seen By Ige Immune Complexes, Rebecca K. Martin, Keith B. Brooks, Frida Henningsson, Birgitta Heyman, Daniel H. Conrad

Microbiology and Immunology Publications

IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes …

Antigen Transfer From Exosomes To Dendritic Cells As An Explanation For The Immune Enhancement Seen By Ige Immune Complexes, Rebecca K. Martin, Keith B. Brooks, Frida Henningsson, Birgitta Heyman, Daniel H. Conrad

Microbiology and Immunology Publications

IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes …

An Emerging Mycoplasma Associated With Trichomoniasis, Vaginal Infection And Disease, Jennifer M. Fettweis, Myrna G. Serrano, Bernice Huang, J. Paul Brooks, Abigail L. Glascock, Nihar U. Sheth, Vaginal Microbiome Consortium, Jerome F. Strauss Iii, Kimberly K. Jefferson, Gregory A. Buck

Microbiology and Immunology Publications

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as “Mnola.” In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from …

An Emerging Mycoplasma Associated With Trichomoniasis, Vaginal Infection And Disease, Jennifer M. Fettweis, Myrna G. Serrano, Bernice Huang, J. Paul Brooks, Abigail L. Glascock, Nihar U. Sheth, Vaginal Microbiome Consortium, Jerome F. Strauss Iii, Kimberly K. Jefferson, Gregory A. Buck

Microbiology and Immunology Publications

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as “Mnola.” In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from four …

Virginia Commonwealth University Fall Commencement Program [2014], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Virginia Commonwealth University Graduate And Professional Programs Bulletin Courses [2014], Virginia Commonwealth University

VCU Bulletins

Listing of professional and graduate courses for 2014-2015.

Make Art Real, Grace E. Harris Leadership Institute, Virginia Commonwealth University, Dolores Carrington-Hill, M. Teresa Doherty, Alison Jones, Michelle Mcgregor, Mike Porter, W. Scott Street, Patricia White

L. Douglas Wilder School of Government and Public Affairs Publications

The Make Art Real project aims to introduce new audiences to the arts. It supports Theme II of VCU’s Quest for Distinction by promoting and fostering creative expression through innovative collaborations. The project involves displaying existing connections between art and non-art disciplines, as well as making new connections. These unusual pairings are then placed on exhibition through a lunch-time lecture series named “Unexpected_Connections,” which allow faculty, staff, and students to lead and participate in discussions about the reality of art. The lecture series is the first sustainable and reoccurring program to be held in the Depot building, a multidisciplinary facility …

Clinical Features And Genetic Analysis Of 20 Chinese Patients With X-Linked Hyper-Igm Syndrome, Lin-Lin Wang, Wei Zhou, Wei Zhao, Zhi-Qing Tian, Wei-Fan Wang, Xiao-Fang Wang, Tong-Xin Chen

Pediatrics Publications

X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days–21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea …

Measuring Hiv Stigma At The Family Level: Psychometric Assessment Of The Chinese Courtesy Stigma Scales (Ccsss), Hongjie Liu, Yongfang Xu, Yehuan Sun, Levent Dumenci

Social and Behavioral Sciences Publications

Courtesy stigma is the stigmatization a person perceives or experiences due to their association with a stigmatized individual or group. Most HIV-related stigma scales have been developed for people living with HIV/AIDS (PLWHAs), but not for their HIV-uninfected family members. To date, few measurement scales have been designed to measure the degree of stigma among both PLWHAs and their HIV-uninfected family members at the family level. We developed a set of courtesy stigma scales and estimated their reliability and validity from 256 PLWHAs and 256 of their HIV-uninfected family members. Exploratory and confirmatory factor analyses were performed in two independent …

The Effect Of Fluvastatin On Mast Cell Function: Genotype Dependence, Elizabeth M. Kolawole

Theses and Dissertations

Fluvastatin, the HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has more recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, which effects one third of America’s population, we assessed the effect of fluvastatin on mast cell and basophils function. We demonstrate that fluvastatin downregulated IgE-mediated cytokine production. Additionally, in vivo studies showed that fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, the effects of fluvastatin showed dependence on genetic background, as C57BL/6 mast cells were sensitive, while …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

Understanding Ligand Binding, Selectivity And Functions On The G Protein-Coupled Receptors: A Molecular Modeling Approach, Saheem Zaidi

Theses and Dissertations

The assessment of target protein molecular structure provides a distinct advantage in the rational drug design process. The increasing number of available G protein-coupled receptor crystal structures has enabled utilization of a varied number of computational approaches for understanding the ligand-receptor interactions, ligand selectivity and even receptor response upon ligand binding. The following dissertation examines the results from three different projects with varied objectives – i) structural modeling of human C-C chemokine receptor type 5 (CCR5) and assessment of the ligand binding pocket of the receptor, ii) assessment of the selectivity profile of naltrexone derivatives on the three opioid receptors …

Identification Of Peptidases In Highly-Pathogenic Versus Weakly-Pathogenic Naegleria Fowleri Amebae, Ishan Vyas

Theses and Dissertations

Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic Meningoencephalitis. Highly-pathogenic mouse-passaged amebae (Mp) and weakly-pathogenic axenically-grown (Ax) N. fowleri were examined for peptidase activity. Zymography and azocasein peptidase activity assays demonstrated that Mp and Ax N. fowleri exhibited a similar peptidase pattern. Prominent for whole cell lysates, membranes and conditioned medium from Mp and Ax amebae were the presence of an activity band of approximately 58kDa and 100 kDa bands susceptible to the action of cysteine and metallopeptidase inhibitors, respectively. Further roles of the peptidases during the invasion process were examined by in vitro invasion assays …

Using Structural Analysis To Investigate The Function Of Suppressor Of Ikk-Epsilon (Sike), Sean W. Mckinley

Theses and Dissertations

The innate immune system provides the body’s first line of defense against pathogenic challenge through pathogen recognition and initiation of the immune response. Among the various cellular mechanisms of pathogen recognition in mammals, Toll-like receptor 3 (TLR3) recognizes viral dsRNA. Stimulation of TLR3 signaling pathway leads to transcription of pro-inflammatory cytokines and type-1 Interferons. Suppressor of IKKε (SIKE) interacts with two kinases in the signaling pathway, IKKε and TANK binding kinase 1 (TBK1), inhibiting the transcription of type I interferons. Recently, the Bell Laboratory discovered that SIKE blocks TBK1-mediated activation of type I interferons by acting as a high affinity, …

Characterization Of The Effects Of Iron On Neisseria Gonorrhoeae Surface Protein Modulation And Host Cell Interactions, Aminat Oki

Theses and Dissertations

Iron is an essential nutrient that is sequestered by iron-binding proteins in the human host resulting in a hostile environment for microbes. Neisseria gonorrhoeae, however, can utilize numerous iron-binding proteins such as transferrin and lactoferrin to acquire this nutrient. During initial infection, gonococci have access to transferrin and lactoferrin present in semen and vaginal fluids, as well as to hemoglobin present in blood during menses or disseminated infections. Consequently, the gonococcus likely encounters conditions of high iron at some stages in the course of natural infection. Potential contributions of iron to gonococcal invasion have however been largely over looked in …

The Role Of Toll-Like Receptor 9 In Periodontitis, Paul Kim

Theses and Dissertations

Periodontitis is a biofilm-initiated inflammatory disease, resulting in soft tissue damage and alveolar bone loss. A nucleic acid sensor, toll-like receptor 9 (TLR9), has been recently implicated in periodontal inflammation. This study utilized an in vivo periodontitis model using TLR9 knockout (TLR9-/-) mice to assess the role of TLR9 in periodontitis. Significant bone loss was observed in wild type, but not in TLR9-/- mice. Further experiments using ex vivo assays revealed significantly higher IL-6 production in splenocytes of wild type mice compared to knockout cells in response to Porphyromonas gingivalis (a keystone pathogen for periodontitis) challenge. In conclusion, TLR9 contributes …

A Route To Discover Small Molecule Inhibitors Of Psaa, A Potential Target For Streptococcus Pneumoniae, Ahmad J. Obaidullah

Theses and Dissertations

Due to the development of multidrug resistance in Streptococcus pneumoniae, research has begun to define new drug targets for pneumonia therapy. Different research groups have identified a lipoprotein, PsaA that is important for pneumonia virulence. PsaA is a manganese transporter that is required for bacterial virulence and growth. We have employed computer modeling to virtually screen a small-molecule database for inhibition of PsaA function by targeting the metal binding pocket, performing receptor-based virtual screening and molecular docking and scoring to identify potential inhibitors of PsaA function. We have developed an assay for screening compounds, including the use of a PsaA …

The Influence Of Dementia Caregiver Mental Health On Quality Of Care In Argentina, Alejandra Morlett Paredes

Theses and Dissertations

This study examined the connections between cognitive functioning in individuals with dementia and caregiver burden, burden and mental health, mental health and quality of care. One hundred two dementia caregivers from San Lucas, Argentina completed questionnaires assessing these constructs. Caregiver burden, depression, anxiety, and satisfaction with life explained 18.8% of the variance in quality of care – respect and 14.7% of the variance in quality of care – provide. An SEM with generally adequate fit indices uncovered that cognitive functioning in individuals with dementia was inversely associated with caregiver burden, caregiver burden was inversely associated with mental health, and mental …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Characterization Of Tonb-Dependent Metal Transporters Within Neisseria Gonorrhoeae, Mary Kathryne Dickinson

Theses and Dissertations

Neisseria gonorrhoeae, the etiologic agent of gonorrhea, utilizes TonB-dependent transporters to import essential nutrients such as iron. Study of TonB-dependent transporters is extremely important due to the fact that they make excellent vaccine targets. In order to learn more about the structure, function, expression, and regulation of selected TonB-dependent transporters, three goals were established for this study. The first goal was to examine the role of two highly conserved regions of TbpB in lipidation. One of the conserved regions of TbpB, the LSAC motif, was shown to be critical for lipidation. The second goal was to determine whether MisR/MisS regulates …

Receptor Of Advanced Glycation Endproducts (Rage) Is Positively Correlated With Tumor Necrosis Factor-Α In Adolescents With Obesity, Tasnim Rahman, Daniel H. Conrad, Anshu Gupta

UROP Posters

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty …

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

UROP Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Clostridium Difficile Infection Occurrence In Academic Health Centers: Do Organizational Factors Matter?, Amy Pakyz

Theses and Dissertations

Healthcare-associated infections occur commonly in hospitals and have a major impact on patient well-being. The occurrence of the healthcare-associated infection, Clostridium difficile, has been occurring more frequently among hospitalized patients due to an epidemic strain, and is an important cause of antibiotic-associated diarrhea and colitis. This study examined the impact of several organizational factors on the occurrence of C. difficile infection (CDI) in hospitals using an institutional theory perspective. Administrative claims were utilized from University HealthSystem Consortium hospitals to obtain hospital-level data for the calendar year 2011. Data were available for 89 hospitals. Hospital-level analyses, negative binomial regression models, were …

Metabolic Remodeling And Mitochondrial Dysfunction In Maladaptive Right Ventricular Hypertrophy Secondary To Pulmonary Arterial Hypertension, Jose Gomez-Arroyo

Theses and Dissertations

Right ventricular dysfunction is the most frequent cause of death in patients with pulmonary arterial hypertension. Although abnormal energy substrate use has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in failing right ventricular tissue remain incomplete. In the present dissertation we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. Two different rat models of RV hypertrophy were studied. The model of right ventricular failure (SU5416/hypoxia) exhibited a significantly decreased gene expression of peroxisome proliferator-activated receptor- coactivator-1α, peroxisome proliferator- activated receptor-α and estrogen-related receptor-α. The …

Lapatinib And Sorafenib Kill Gbm Tumor Cells In A Greater Than Additive Manner, Seyedmehrad Tavallai

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor in adults, affecting thousands of people worldwide every year, with a life expectancy, post diagnosis of 12 months. Surgery, radiotherapy and chemotherapy together, result in an overall mean survival not exceeding 15 months. Targeted therapeutic agents sorafenib, an oral multi kinase inhibitor, and lapatinib, an epidermal growth factor receptor (EGFR) inhibitor, used in combination have been shown to kill GBM cells be through inhibition of major growth mediating signaling pathways that are frequently over expressed in gliomas, including mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT). …

Work Hope And The Socioemotional Functioning Of Offenders, David Guion

Theses and Dissertations

For offenders returning to society at record levels, securing work looms as one of the most crucial factors in successful reentry. Work hope is a construct that seeks to measure the relative presence of goals of securing desired work, thoughts about how to achieve those goals, and agency to achieve those goals, even in the presence of obstacles. This study sought to examine relationships among work hope, the socioemotional variables of attachment, emotion regulation, physical, relational, and workplace victimization, and coping, and the career-related variables of perceptions of career-related barriers and complexity level of career goals. The sample comprised cohorts …

Older Msm And Hiv/Aids: A Grounded Theory Study To Inform Prevention, Johnnie O'Neal

Theses and Dissertations

This study sought to increase knowledge as it relates to HIV-prevention for older adults, especially for MSM who are HIV-negative. In participating in this study, participants shared their experiences, stories and feelings related to their exposure to HIV and HIV-prevention initiatives. Using a Traditional Grounded Theory method, 22 interviews with older MSM were conducted with the aim of producing a theory that explained how these men lived prior to HIV, the different ways they responded to the onset of the virus, how they have lived their lives over the last three decades, and the extent to which the virus continues …

Commonwealth Times 2013-10-21

Commonwealth Times, 1969-

No abstract provided.

Characterization Of Cyclic Di-Gmp Binding By The Sole Borrelia Burgdorferi And Borrelia Hermsii Pilz Domain-Containing Proteins, Katherine Louise Mallory

Theses and Dissertations

Borrelia burgdorferi and Borrelia hermsii cause Lyme disease and relapsing fever, respectively. These spirochetes are maintained in an enzootic cycle, involving tick vectors and mammalian hosts. Differential gene expression is central in their survival in various environmental conditions. C-di-GMP has been demonstrated to be important in bacterial adaptation. Borrelia deletion mutant phenotypes have shown that c-di-GMP regulates motility, infectivity, and enzootic cycle progression. As the only known receptors encoded by Borrelia, PlzA and PlzC characterization is necessary in delineating c-di-GMP roles within the cell. In this study, biochemical, biophysical, and FRET methods demonstrated that these proteins exhibit a structural rearrangement …