The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin

Theses and Dissertations

Breast cancer is the second leading cause of death amongst women ages 20 to 59. Despite advancements in cancer therapies, more research is necessary to improve the diagnoses and treatment of several types of breast cancer. Paclitaxel (Taxol) is a commonly utilized anti-cancer drug for various types of solid tumors. However, the molecular mechanism utilized by paclitaxel to induce cell death is still elusive. Previous studies in our laboratory have shown that the pro-apoptotic BCL-2 family protein, BAK (BCL-2 homologous antagonist/killer) plays an important role in paclitaxel-induced cell death. In untreated breast cancer cells, BAK is associated with the anti-apoptotic …

Assembly And Mechanical Characterization Of Suspended Boron Nitride Nanotubes, Rachel Waxman

Theses and Dissertations

This study details the dielectrophoretic assembly and mechanical characterization of boron nitride nanotubes on silicon chips with gold electrodes. The chips were fabricated from 4in round silicon wafers with a 100nm-thick low stress silicon nitride insulating layer on the top and bottom. The electrodes were patterned using photo- and electron-beam lithography and dry etching, and the wafers were cut into 4 x 6mm chips. The boron nitride nanotubes studied were obtained from NIA and were synthesized via a unique pressurized vapor/condensor method, which produced long, small-diameter BNNTs without the use of a catalyst. These nanotubes were studied due to their …

Characterization Of Complement Evasion Of The Periopathogen, Treponema Denticola, Daniel Patrick Miller

Theses and Dissertations

Periodontitis is a polymicrobially-induced, chronic inflammatory disease of the tissues that support and surround the tooth. While greater than 500 organisms are found in dental plaque, Treponema denticola is one of only a few species associated with disease. It has been hypothesized that oral bacteria disrupt host homeostasis through manipulation of the innate immune system. In this study, we examine the impact of binding and subsequent cleavage of factor H, a complement regulator, by T. denticola in the evasion and subversion of complement. The molecular interaction between the sole FH-binding protein, FhbB, and FH was detailed by x-ray crystallography, site-directed …

Folate Conjugated Dendrimers For Targeted Anticancer Therapy, Shannon Andrews

Theses and Dissertations

Anticancer therapeutics are often limited to suboptimal doses due to their lack of selectivity for tumor cells and resultant damage to healthy tissue. These limitations motivated researchers to develop tumor-specific delivery systems for improved therapeutic efficacy and reduced unintended cytotoxicity. Polyamidoamine dendrimers offer an ideal platform for designing targeted therapeutics with tunable characteristics that optimize pharmacokinetic behavior and targeting specificity. Ligand conjugation to dendrimer provides the biochemical interaction necessary to activate tumor-specific receptors for receptor-mediated endocytosis and effective internalization of polyplexes. Tumor-specific receptors overexpressed in carcinomas, like folate receptor-alpha (FOLRα), are targeted by ligand-conjugated dendrimer to allow enhanced internalization of …

Evaluating The Antibody Response Against Ospa, Ospc, And Ospe Recombinant Proteins Over Time In Borrelia Burgdorferi Positive Serum Samples, Bridget Dillon

Theses and Dissertations

Lyme disease is the most common tick-borne illness in North America. It can be hard to detect using blood tests, especially in the early stage. Due to the number of significant complications from untreated or undertreated Lyme disease, better methods need to be found to detect the disease. Some surface lipoproteins may be used to detect early disease due to their early expression. Others are maintained for the duration of the infection and can be used to detect chronic Lyme disease. Antibody responses to OspA, OspC and OspE were measured in sera from experimentally infected dogs. The response to OspA …

Characterization Of A Putative Tonb Deficient Porphyromonas Gingivalis Mutant, Soheil Rostami

Theses and Dissertations

Porphorymonas gingivalis is one of the major bacterial pathogens responsible for the initiation and progression of periodontal disease. The bacterium requires hemin uptake for its growth and has developed sophisticated mechanisms to extract hemin from hemin containing proteins in the oral cavity. Hemin first binds to receptors on the surface of P. gingivalis and is then taken up in an energy dependent manner. TonB is an inner membrane bound protein that spans the periplasm and is believed to be involved in the passage of hemin through the double membrane of P. gingivalis. However, the TonB protein in P. gingivalis is …

Predicting And Classifying Packet Transmission Efficiency In Bio-Inspired Wireless Sensor Networks, Ahmad Alkazzaz

Theses and Dissertations

Biological networks (specifically genetic regulatory networks) are known to be robust to various external perturbations. Bio-inspired wireless sensor networks (WSN) are known to be smart communication structures and have a have high packet transmission efficiency. In earlier work neural network models that correlate the average packet receival rates to the five topological features of the bio-inspired WSN were investigated. These features include the degree index, sink coverage, network density, hub node density, and motif index. In this thesis, an appropriate classification algorithm that works with these five features is investigated. The random forest algorithm is the best classification algorithm compared …

The Total Picture: Multiple Chemical Exposures To Pregnant Women In The Us – An Nhanes Study Of Data From 2003 Through 2010, Teri Cabana

Theses and Dissertations

INTRODUCTION: Chemical exposures to US pregnant women have been shown to have adverse health impacts on both mother and fetus. A prior paper revealed that US pregnant women in 2003-2004 had widespread exposure to multiple chemicals. The goal of this research is to examine how environmental chemical exposures to US pregnant women have changed from 2003 to 2010 and to look further at the extent of simultaneous exposure to multiple chemicals in US pregnant women using biomonitoring data available through NHANES (the National Health and Nutritional Examination Survey). METHODS: Using available NHANES data from the following cycles (2003-2004, 2005-2006, 2007-2008, …

Multi-Species Gene Networks And Drosophila Ethanol Sedation, Arnavaz Kollah

Theses and Dissertations

Alcohol use disorders (AUDs) are major health issues with few known genetic explanations. This project used the fruit fly (Drosophila melanogaster) model to identify genes and gene networks that influence alcohol intoxication, a phenotype related to alcohol abuse in humans. We used bioinformatic tools to build gene networks based on 24 published Drosophila ethanol-responsive genes with human orthologs. We then assessed the role of these networks in ethanol sedation by testing two of the networks seeded on IP3K2, a gene that regulates calcium signaling, and CG14630, a gene involved in carnitine biosynthesis. We knocked down several genes in each of …

Reproductive Success In Hatchery-Produced Eastern Oyster, Crassostrea Virginica (Gmelin), April Piggott

Theses and Dissertations

The eastern oyster (Crassostrea virginica Gmelin 1791) has great ecological and economic importance but populations have declined, especially in Chesapeake Bay, to historically low numbers. Hatcheries strive to produce oysters with beneficial characteristics for supplementation and commercial purposes, both natural and stimulated mass spawning. Unequal contribution of parents in mass spawnings potentially can lead to high levels of inbreeding and a loss of beneficial characteristics in offspring. In this study, we determined microsatellite genotypes for parents (n^parents =24, 49, and 77 parents) and progeny (n=96 each) of three hatchery-produced families and used the data for parental assignment. We observed the …

Investigations Into The Fluorescent Covalent Labeling Of Biomolecules Utilizing Rhodamine Dyes, Electrophilic Leaving Groups And Mrna Display., Susan D. Selaya

Theses and Dissertations

The discovery of a method by which proteins of interest can selectively be labeled with a probe of choice intracellularly is a longstanding goal in chemical biology research. Conventional labeling techniques have utilized large domain tags but despite the development of small labeling molecules there have been no short peptide sequences known to covalently label a small molecule without the aid of an enzymatic process or metal chelation. We aimed to find a sequence of nucleophilic peptides that reacted covalently and specifically with electrophilic small labeling molecules using mRNA display. Our goal was to show that an electrophilic small labeling …

Characterization Of Suppressor Of Ikkepsilon Function Using Immunofluorescence Assays And Quantitative Colocalization Analysis, Kenneth F. Lawrence

Theses and Dissertations

During viral infections, Toll-like receptor-3 (TLR3) stimulation initiates signaling to activate transcription of pro-inflammatory cytokines and type-1 interferons. Suppressor of IKK-ε (SIKE) interacts with two kinases in the signaling pathway, IKK-ε and TANK-binding kinase 1 (TBK1), inhibiting the transcription of type I interferons. Recently, this laboratory discovered that SIKE blocks TBK1-mediated activation of type I interferons by acting as a high affinity, alternative substrate of TBK1. Co-immunoprecipitation (co-IP) assays suggested that the SIKE interaction network impinged upon the cytoskeleton and RNA transport. To characterize SIKE’s function within the antiviral response, SIKE’s role in RNA transport and cytoskeletal rearrangements was targeted …

Development And Preliminary Validation Of The Youth Therapist Observational Cultural Competence Scale, Carrie Tully

Theses and Dissertations

The increasing diversity of the United States creates a pressing public health need to investigate methods to increase the engagement, retention, and efficacy of mental health services for racial/ethnic minority (REM) youth. Evidence from the adult psychotherapy treatment literature suggests that enhancing therapist cultural competence leads to increases in client satisfaction, alliance, and retention (Constantine, 2002; Sodowsky, Kuo-Jackson, Richardson, & Corey, 1998; Worthington, Soth-McNett, & Moreno, 2007). However, this relationship has not been adequately explored in youth mental health services, due in part, to a lack of valid and reliable measurement. This research project included measure development and initial validation …

Theorizing When User Reaction To It Implementation Is Neither Resistance Nor Acceptance, But Constructive Behavior: A Case Study Of Healthcare It Implementation, Kaveh Mohajeri

Theses and Dissertations

The prevailing discourse of “resistance vs. acceptance” in IT implementation research mostly personalizes the issue as “users” versus IT implementers (e.g., managers, CIOs, CMIOs, etc.). This kind of discourse has created an IT-implementer-centric attitude among IS scholars and practitioners. The IT-implementer-centric attitude, while embraces “acceptance” as a desirable reaction almost unconditionally, frequently holds for minimizing or more conservatively suppressing “resistance” to IT implementation. In other words, the mainstream IT implementation research, almost completely, treats “users” as passive recipients whose choices, as they face pre-developed/pre-designed/pre-rolled-out technology being implemented, can only be defined on a spectrum from “acceptance” to “resistance.” The current …

Design And Validation Of A Computational Model For Study Of Scapholunate Joint Kinematics, Edward J. Tremols

Theses and Dissertations

As computational power has increased, computational modeling has become a very promising tool to model the biomechanics of complex joint systems. Musculoskeletal computational models have become more complex when compared to original iterations which utilized a number of simplifications. This thesis utilized a three-dimensional computational model of the wrist joint structure to investigate scapholunate kinematics. The model accurately represented the bony anatomy of the wrist and hand and represented soft tissue structures such as ligaments, tendons, and other surrounding tissues. Creation of the model was done using commercially available computer-aided design and medical image processing software, and utilized the rigid …

The Contribution Of Parent Psychosocial Functioning To Parental Monitoring, Youth Adherence, And Glycemic Control During Adolescence, Elizabeth M. Robinson

Theses and Dissertations

Objective: Type 1 diabetes is one of the most common pediatric chronic illnesses. Adolescents are at risk for poorer adherence and in turn, poorer glycemic control; however, youth whose parents remain involved in diabetes care are in better control. A parent’s level of involvement is dependent in part upon his or her own social and emotional functioning. Much is known about the link between separate aspects of parent psychosocial functioning (e.g., depressive symptoms, parental stress) and parent involvement in diabetes care, adherence, and glycemic control. However, no study to our knowledge has examined these constructs simultaneously as they interrelate …

Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn

Theses and Dissertations

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …

Mda-9/Syntenin: From Glioblastoma Pathogenesis To Targeted Therapy, Timothy P. Kegelman

Theses and Dissertations

The most common malignant glioma, glioblastoma multiforme (GBM), remains an intractable tumor despite advances in therapy. Its proclivity to infiltrate surrounding brain tissue contributes greatly to its treatment failure and the grim prognosis of patients. Radiation is a staple in modern therapeutic regimens, though cells surviving radiation become more aggressive and invasive. Consequently, it is imperative to define further the cellular mechanisms that control GBM invasion and identify promising novel therapeutic targets. Melanoma differentiation associated gene-9 (MDA-9/Syntenin) is a highly conserved PDZ domain-containing scaffolding protein that promotes invasion and metastasis in human melanoma models. We show that MDA-9/Syntenin is robustly …

Synthetic, Sulfated, Lignin-Based Anticoagulants, Akul Mehta

Theses and Dissertations

Chemoenzymatically synthesized low molecular weight lignin polymers have been previously found to be potent inhibitors of a number of serine proteases via allosteric mechanisms targeting heparin binding sites. Herein, we describe the creation of synthetic sulfated β-O4 lignin (SbO4L) polymer, which is more homogenous compared to previous lignins with respect to its inter-monomeric linkage. SbO4L is a selective inhibitor of thrombin and plasmin. SbO4L was found to act via a unique mechanism targeting thrombin exosite 2 in a manner similar to platelet glycoprotein Ibα (GPIbα). Advanced hemostasis and thrombosis assays demonstrated that SbO4L acts via a dual mechanism: as an …

Platinum Complexes And Zinc Finger Proteins: From Target Recognition To Fixation, Samantha Tsotsoros

Theses and Dissertations

Bioinorganic chemistry strives to understand the roles of metals in biological systems, whether in the form of naturally occurring or addition of non-essential metals to natural systems. Metal ions play vital roles in many cellular functions such as gene expression/regulation and DNA transcription and repair. The study of metal-protein-DNA/RNA interactions has been relatively unexplored. It is important to understand the role of metalloprotein interactions with DNA/RNA as this enhanced knowledge may lead to better understanding of diseases and therefore more effective treatments. A major milestone in the development of this field was the discovery of the cytotoxic properties of cisplatin …

Regulation Of Ykl-40 In Sterile Inflammation And Its Role In Glioblastoma In Vivo, Reetika Bhardwaj

Theses and Dissertations

YKL-40 is a secreted glycoprotein, which is a shared biomarker of chronic inflammation and oncogenic transformation. Indeed, YKL-40 expression is up-regulated in many diseases including multiple sclerosis, Alzheimer disease, viral encephalitis, HIV-associated dementia, brain infarction, and traumatic brain injury. YKL-40 is also expressed by several solid tumors, such as osteosarcoma, ovarian carcinoma and glioblastoma multiforme (GBM). It promotes the migration and invasion of astrocytes as well as GBM cells. Serum YKL-40 levels have been shown to directly correlate with tumor grade and potentially tumor burden in GBM. In contrast to the numerous reports documenting elevated expression of YKL-40, relatively little …

Developing A Caenorhabditis Elegans Model For Marfan Syndrome, Pauline Fotopoulos

Theses and Dissertations

Marfan Syndrome (MFS) is one of the most common monogenic diseases and affects approximately 1 in 5,000 individuals worldwide. The syndrome is characterized by elongated extremities, tall stature, slender frame, and cardiac, and vision abnormalities due to severe connective tissue defects. It is caused by mutations in the fbn1 gene, which encodes an extracellular matrix glycoprotein, and is required for proper cardiac and skeletal development and for sequestration of TGFβ (transforming growth factor beta) and BMP (bone morphogenetic protein) within the extracellular matrix (ECM). The primary objective of this study was to establish a C.elegans MFS model and use this …

Global Assessment Of Radiocarbon Isotopic Analysis For Particulate And Dissolved Organic Carbon In Riverine Systems, Ashley Tucker

Theses and Dissertations

Rivers are a significant source of particulate and dissolved organic carbon (POC, DOC) into inland waters and coastal systems and provide a fundamental linkage between the terrestrial, oceanic, and atmospheric carbon reservoirs. Recent studies have examined the relationship between the quantity and form (POC vs. DOC) of carbon delivered to the aquatic system; however, little is known about the age of POC and DOC exported and how the radiocarbon age may vary with latitude, topographic gradient, vegetation, and land use. I provide the first global synthesis of published radiocarbon values of POC and DOC (∆14C). Inclusion of DOC and POC …

Effects Of Dissolved And Dietary Microcystin On Clearance Rates Of Wedge Clams (Rangia Cuneata) In The Tidal Fresh James River, Spencer Tassone, Paul Bukaveckas, Joe Wood

UROP Posters

Benthic filter feeders are important organisms in estuaries due to their ability to remove algal and non-algal particulate matter from the water column. Microcystin (MC) is a cyanotoxin that is known to have adverse effects on diverse consumers, though its effects on benthic filter-feeders are not well-studied. In this study, we examine the effects of microcystin on the filtering activities of Rangia cuneata, a common and often dominant filter-feeder in tidal freshwaters. Clams and seston obtained from the James River were used along with commercially-available microcystin to measure clearance rates of Rangia across a gradient of dissolved microcystin concentrations. We …

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 …

Environmental Regulation Of Tidal Wetland Microbial Communities And Associated Biogeochemistry, Ember Morrissey

Theses and Dissertations

Microbial communities play an essential role in carrying out the biogeochemical cycles that sustain life on Earth, yet we know very little about their ecology. One question of particular interest is how environmental conditions shape microbial community structure (i.e., the types of organisms found in the community and their relative abundance), and whether such changes in structure are related to biogeochemical function. It is the aim of this dissertation to address this question via the examination of carbon (C) and nitrogen (N) cycling in wetland ecosystems, which due to their diverse hydrology have a profound influence on biogeochemical cycles. With …

[2013-12-13] Meeting Of The Academic And Health Affairs Policy Committee, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.

[2013-12-13] Meeting Of The Board Of Visitors Of Virginia Commonwealth University, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.

Real Time Monitoring Of Surface Chemical Events By Streaming Potentials In Microfluidic Channels, Kenji Nokura

Theses and Dissertations

Zeta potential is one of the tools to measure the surface charge of materials, and Alvarez et al. have developed a microchannel device to measure zeta potentials in real time for label-free sensing using immobilized receptors on microchannel surfaces. However, the challenge has been the charge interference of surface modifiers on analyte detection. Therefore, it was necessary to find the best strategy to regenerate minimal surface charge after modifying the channel with polymer films that would anchor the affinity groups for the analyte. It was demonstrated that adsorption of positively and negatively charged analytes were monitored via real time zeta …