Digital Commons Network^™

Dynamic Regulation Of Mitochondrial Stat3 And Its Association With Cypd, Jeremy A. Meier

Theses and Dissertations

In recent years, a number of nuclear transcription factors have been shown to be present in the mitochondria where they have distinct roles in regulating mitochondrial function. Signal Transducer and Activator of Transcription 3 (STAT3), classically activated by the JAK family of receptor associated tyrosine kinases to drive nuclear gene expression, is one such transcription factor with a unique mitochondrial role. There, it has been shown to support oxidative phosphorylation, regulate mitochondrial-encoded transcripts, and be key for the transformation and growth of a number of different cancers. Despite its well-characterized functional importance at the level of the mitochondria, the mechanism …

Adducins Are Negative Regulators Of Migration And Invasion Of Normal Lung Epithelial Cells And Lung Cancer Cells, Parth Hitenbhai Amin, Parth Amin

Theses and Dissertations

Cell migration is an important component of many physiological and pathological processes such as tissue and organ morphogenesis during development, wound healing, inflammatory immune response, and tumor metastasis. The actin cytoskeleton is the basic engine driving cell migration. In the present study, we elucidate the role of an important actin interacting proteins, Adducins, in motility of normal lung epithelium and lung cancer cells. Adducins are the family of cytoskeleton protein capping the fast growing end and facilitating the bundling of actin filaments. Adducins are encoded by the three closely related genes namely alpha (ADD1), beta (ADD2) and gamma (ADD3) Adducin. …

Substrate Recognition And Mechanistic Studies Of Protein N-Terminal Methyltransferase 1, Yunfei Mao

Theses and Dissertations

The methylation at the α-N-terminal amines of proteins that start with a canonical motif X-P-K (X=A/P/S) has been a known modification for nearly four decades. In 2010, protein α-N-terminal methyltransferase 1 (NTMT1/NRMT1) was identified as the first enzyme responsible for this modification. NTMT2 was discovered as a second member belonging to this family, but it was reported as a mono-methylase. The identification of RCC1, retinoblastoma (Rb) protein, centromere protein-A/B (CENP-A/B), and DNA damaged-binding protein 2 (DDB2) as new NTMT1 substrates revealed NTMT1’s biological significance in mitosis, cell-cycle regulation, centromere formation, and damaged DNA repair, respectively. Although significant progress had been …

Irreversible Zinc Block Of The Swelling-Activated Chloride Current In Di Tnc1 Astrocytes, Noah Belkhayat

Theses and Dissertations

The swelling-activated chloride current, commonly referred to as ICl,swell, is an outwardly-rectifying anion current that plays an important role in cell volume regulation, among other capacities. Despite several decades of research, the molecular identity of the channel responsible for this chloride current remains controversial. Recent indications that key endogenous sulfhydryl groups are capable of modifying the current led us to assess the effects of several divalent cations, including zinc, on ICl,swell. Zinc is known to tightly associate with sulfhydryl groups such as in zinc finger proteins. We found that extracellular zinc irreversibly inhibited ICl,swell at a site downstream in the …

A Weighted Gene Co-Expression Network Analysis For Streptococcus Sanguinis Microarray Experiments, Erik C. Dvergsten

Theses and Dissertations

Streptococcus sanguinis is a gram-positive, non-motile bacterium native to human mouths. It is the primary cause of endocarditis and is also responsible for tooth decay. Two-component systems (TCSs) are commonly found in bacteria. In response to environmental signals, TCSs may regulate the expression of virulence factor genes.

Gene co-expression networks are exploratory tools used to analyze system-level gene functionality. A gene co-expression network consists of gene expression profiles represented as nodes and gene connections, which occur if two genes are significantly co-expressed. An adjacency function transforms the similarity matrix containing co-expression similarities into the adjacency matrix containing connection strengths. Gene …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

Evaluating The Pennebaker Paradigm With Bereaved Emerging Adults: Applications Of Text Analysis, Elizabeth A. Collison

Theses and Dissertations

Bereavement is an important research area as it can result in grief reactions that lead to serious psychological and health consequences, particularly for the at-risk group of emerging adults (Arnett, 2000; Balk, Walker, & Baker, 2010; Fisher, Murray, & Frazer, 1985; Stroebe, Schut, & Stroebe, 2007). Expressive writing is a well-researched intervention for trauma and adjustment, yet research repeatedly has revealed null results with the classic Pennebaker paradigm as a bereavement intervention (Stroebe et al., 2002; Stroebe, Schut, & Stroebe, 2006). It may be premature, however, to conclude expressive writing is ineffective for the bereaved due to limitations in extant …

Investigating The Mechanism Of The Compartmentalized Cbp (Creb-Binding Protein) Ubiquitin Ligase Activities, Oluwatoyin E. Akande

Theses and Dissertations

CBP (CREB Binding Protein) is global transcriptional co-activator and histone acetyltransferase. CBP is involved in the modulation of the transcription of many genes via histone acetylation at the promoter regions of the target genes. Also, non-histone proteins and transcription factors can be acetylated by CBP to promote their transcriptional activation. In addition to its transcription co-activator role, CBP is involved in many other pathological and physiological cellular processes such as cell growth and differentiation, cell transformation and development, response to stress, cell cycle regulation and apoptosis.

CBP and its paralogue p300, play double-edged roles in the regulation of p53, a …

Involvement Of Signal Peptidase I In Streptococcus Sanguinis Biofilm Formation, Jessica Aynapudi

Theses and Dissertations

Biofilm accounts for 65%-80% of microbial infections in humans. Considerable evidence links biofilm formation to oral disease and consequently systemic infections. Eradication of biofilm-associated infections is important. Streptococcus sanguinis, a Gram-positive bacterium, is one of the most abundant species in oral biofilm. It contributes to biofilm development in oral cavities and is one of the recognized causes of infective endocarditis. To study and identify biofilm genes in S. sanguinis, biofilm formation of 51 mutants was compared with the wild type SK36 strain using crystal violet (CV) staining in a microtiter plate. Confocal laser scanning microscopy (CLSM) and image analysis was …

Upper Thermal Limits Differ Among Component Species In A Host-Parasitoid-Hyperparasitoid System, Kanchan A. Joshi

Theses and Dissertations

Among the predicted impacts associated with global climate change, warming is of special interest because the rates of physiological processes are temperature-dependent. Insects and other ectotherms are likely to be affected due to their limited ability to control body temperature. In this study, I measured the tolerance to extreme high temperatures, i.e., critical thermal maximum (CT_max), of component species in a tri-trophic system, including an herbivore (Manduca sexta), a primary larval parasitoid (Cotesia congregata) and a hyperparasitoid (genus Silochalcis). For wild insects, the parasitoid had the lowest CT_max, the hyperparasitoid had …

A Correlational Analysis Of Secondary Data For Factors Influencing Graduation From Adult Drug Court, David N. Masri

Theses and Dissertations

The proliferation of drug courts throughout the world over the last two decades presents an opportunity and a challenge. The drug court approach involves a combination of treatment and judicial supervision which is a diversion from incarceration and/or ‘traditional’ criminal justice supervision. Despite widespread study of drug courts, there is much that researchers still do not know and there is still controversy as to how and why drug courts work. This research study is an examination of secondary data from an urban, mid-Atlantic drug court to attempt to correlate factors that contribute to success (as defined by graduation) in drug …

Allosteric Effects Of G-Protein Coupled Receptor Heteromerization: Relevance To Psychosis, Jason W. Younkin

Theses and Dissertations

G-protein coupled receptors (GPCRs) implicated in disease are the predominant pharmaceutical targets. Growing evidence suggests that GPCRs form homo- and heteromeric complexes, resulting in allosteric functional changes. Ligands targeting one receptor can alter the function of the other receptor or receptors. Knowledge of these functional changes will provide unique opportunities to treat diseases. We examined two GPCR heteromers implicated in psychosis: mGlu2R-5HT2AR and D2R-5HT2AR. Using whole-cell patch clamp, we studied HEK-293 cells stably transfected with mGlu2R and 5HT2AR. Maximal heteromer formation allows inverse agonists to increase the G-protein activity of the opposite receptor, while sub-maximal heteromer formation does not. However, …

Plant Functional Trait And Hyperspectral Reflectance Responses To Comp B Exposure: Efficacy Of Plants As Landmine Detectors, Paul V. Manley Ii

Theses and Dissertations

At least 110 million landmines have been planted since the 1970s in about 70 nations, many of which remain in place today. Some risk of detection may be mitigated using currently available remote sensing techniques when vegetation is present. My study focused on using plants as phytosensors to detect buried explosives. I exposed three species representing different functional types (Cyperus esculentus (sedge), Ulmus alata (tree), Vitis labrusca (vine)) to 500 mg kg^-1 of Composition B (Comp B; 60/40 mixture of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT)), a commonly used explosive mixture, and measured functional traits and reflectance over …

Celecoxib Enhances Sorafenib/Sildenafil Lethality In Cancer Cells And Reverts Platinum Chemotherapy Resistance, Timothy A. Webb

Theses and Dissertations

The present studies sought to determine whether the lethality of the drug combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also, in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1 and ABCG2. Over-expression of GRP78 and HSP27 maintained pump expression in the presence of drugs. Cell killing …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Drug And Vaccine Development For Neisseria Gonorrhoeaea, Devin R. Cash

Theses and Dissertations

Neisseria gonorrhoeae, the causative agent of the STI gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. One important strategy for gonococcal survival in the host is iron acquisition in the face of nutritional immunity. To overcome iron limitation, the gonococcus expresses TonB dependent transporters (TdTs), outer membrane proteins that facilitate nutrient acquisition. Of the TdTs, the transferrin (Tf), lactoferrin (Lf), and hemoglobin (Hb) receptors hijack iron directly from host proteins, and studies have already shown that the Tf receptor is essential for the initiation of human infection. Given that the TdTs are virulence factors, …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

Vital Pulp Therapy Survivability Based On Radiographic Depth Of Caries, Aaron T. Schmick

Theses and Dissertations

Purpose: The purpose of this retrospective chart review was to determine if the survival of two methods of vital pulp therapy (VPT) were influenced by the pre-operative radiographic depth and location of caries. Methods: Electronic patient records (axiUm®) that contained the procedure codes D3120, Indirect Pulp Therapy (IPT), or D3220, Therapeutic Pulpotomy (TP), were queried. Qualifying charts’ pre-operative and post-operative radiographs were viewed in MiPACS® by two raters. Visit records were queried again to identify any other treatment failures. Results: A total of 568 primary molars met the eligibility criteria. There was a difference in survival depending upon the treatment …

Considerations In The Provision Of Mental Health Services Toward Arabs, Dalia Khoury

Theses and Dissertations

Existing evidence suggests that disparities exist in the use of mental health services by Arabs in the U.S. While there are likely many factors that contribute, lack of cultural competence of mental health providers is one potentially important barrier for mental health service use among racial/ethnic minorities, including Arabs. The primary purpose of this study was to identify and examine factors related to the development and existence of cultural competence toward Arabs. Variables measuring demographics, professional characteristics, familiarity with Arabs, prior experience and knowledge of Arabs, and readiness for change were tested with a randomly selected sample of mental health …

A Mapping System As A Method In Experiential Culture Learning And Engagement, Faisal Mohammad

Theses and Dissertations

From my observation as a new resident in Education City, I recognize a need for cultural awareness and communication amongst those studying and working in this particular area. With this project I propose a different experience, a new way to use experiential learning as a mechanism to change people’s predetermined opinions about one another and disrupt personal biases in order to foster cultural awareness and friendship.

A mapping system or wayfinding strategy to navigate a new city is the beginning of a visitor’s experience in a new place. This new experience is one way for users to identify locations through …

Gender And Sexual Health: Applying Gender Role Theory To Men And Women’S Intention To Engage In Sexual Health Information Seeking Behaviors, Ariella R. Tabaac

Theses and Dissertations

The purpose of the present study is to examine the pathways between gender and behavioral intention to engage in sexual HISB through application of the Theory of Planned Behavior (TPB). It was found that feminine and masculine gender role stress differentially influence perceived behavioral control and behavioral attitudes, and that intention to engage in HISB was higher among women than men. Attitudes and PBC significantly predicted behavioral intention in this model. Further, women in the sample were more likely to search for sexual health information, with online sources being the most frequently reported resource. Additionally, past HISB was a significant …

A Longitudinal Study Of The Motivations For The Non-Medical Use Of Prescription Drugs In A National Sample Of Young Adults, Tess K. Drazdowski

Theses and Dissertations

Young adults are most at-risk for the non-medical use of prescription drugs (NMUPD) and many of its associated negative consequences. Understanding this population’s motivations for use can help to inform efforts to reduce NMUPD. Past research has been limited in scope, consisting primarily of cross-sectional work with college students focusing on prescription stimulants. The current study researched how motivations for NMUPD changed over young adulthood using three waves of data from a longitudinal, nationally representative sample of 14,990 19 to 24 year olds in the Monitoring the Future study cohorts collected between 1976 to 2013. Prescription stimulants, central nervous system …

Serum Vitamin D, Pth, And Calcium Levels In Patients With And Without Early Childhood Caries, Susan A. Meinerz, Harmeet Chiang, Peter C. Moon, Lorin M. Bachmann, Tegwyn Brickhouse, Al M. Best, Tiffany Williams

Theses and Dissertations

Purpose: The purpose was to determine differences in serum vitamin D, parathyroid hormone (PTH), and calcium levels between patients with early childhood caries (ECC) and patients without dental decay.

Materials and Methods: Serum vitamin D, PTH, and calcium levels were obtained from 30 children without dental decay who acted as controls and 60 children with ECC. A questionnaire was filled out by the parent/guardian of each participant consisting of questions regarding medical and dental history, exposure to sources of vitamin D and demographic information.

Results: The difference in the vitamin D levels of the participants was most …

Social Determinants Of Participation In A Home Visitation Fluoride Varnish Program, James E. Puryear, Tegwyn Brickhouse, Caroline Carrico

Theses and Dissertations

Purpose: The purpose of this study is to examine the social determinants of CHIP (Child Health Investment Partnership) of Roanoke Valley children who participated in the preventive oral health program compared to those who did not.

Methods: This is a retrospective cohort study of children (n=2,425) enrolled in CHIP of Roanoke Valley from September 2008-September 2014. Bivariate analysis and multivariable logistic regression models were used to compare age, gender, race, locality, parents’ education level, age at enrollment, and length of enrollment for oral health program participants versus those who did not participate.

Results: Children who were Hispanic …

Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel

Theses and Dissertations

Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …

Analysis Of Radiographic Changes Associated With The Periradicular Diagnosis Of Symptomatic Apical Periodontitis, Preeti Batra

Theses and Dissertations

Symptomatic apical periodontitis (SAP) is indicative of inflammation of the periodontal ligament. It may or may not be accompanied by radiographic changes and may occur with vital or necrotic pulpal diagnosis. Purpose of this study was to analyze clinical and radiographic presentations of SAP in a retrospective electronic dental chart and digital radiograph review utilizing the endodontic diagnostic template note of predoctoral dental school patients presenting with SAP. The aim was to determine prevalence of periapical radiolucencies (PARLs) in SAP, association of SAP to pulpal diagnosis, and define associated radiographic changes. Most prevalent pulpal diagnosis with SAP was symptomatic irreversible …

Design And Structure-Activity Relationship Of Small Molecule C-Terminal Binding Protein (Ctbp) Inhibitors And Investigation Of The Scope Of Palladium Multi-Walled Carbon Nanotubes (Pd-Mwcnt) Catalyst In C–H Activation Reactions, Sudha Korwar

Theses and Dissertations

C-terminal binding proteins (CtBPs) are transcriptional co-repressors involved in developmental processes, and also implicated in a number of breast, ovarian, colon cancers, and resistance against cancer chemotherapy. CtBP is a validated novel potential anti-cancer target. In this project we sought to develop potent and selective small-molecule inhibitors of CtBP. Using a combination of classical medicinal chemistry and modern computational approaches, we designed a potent inhibitor HIPP (hydroxyimino-3-phenylpropanoic acid) that showed an IC₅₀ of 0.24 μM against recombinant CtBP. Further elucidation of the structure-activity relationship (SAR) of HIPP led to the design of more potent inhibitors 3-Cl HIPP (CtBP IC …

The Study Of The Regulon Of Oxyr In Escherichia Coli And Porphyromonas Gingivalis, Christopher K. Pham

Theses and Dissertations

The facultative anaerobe, Escherichia coli and the obligate anaerobe, Porphyromonas gingivalis are two bacteria that reside in our body. Although they reside in separate environments, they are both subject to hydrogen peroxide stress and have mechanisms to regulate the stress. OxyR is the primary transcriptional regulator/sensor of oxidative stress response caused by hydrogen peroxide. OxyR in P. gingivalis is not well-characterized compared to OxyR in E. coli. We sought to characterize and compare the two forms of OxyR in order to gain a better understanding of the protein. We determined the oligomeric state of both proteins: primarily a tetramer for …

Perception Of Profile Appearance As Judged By Peers Using 3d Video Imaging, Megan G. Schuler

Theses and Dissertations

The purpose of this study was to investigate the social perceptions of subjects with differing lip position and facial convexity in three dimensions. A 3dMD camera (3dMD, Atlanta, GA) was used to capture 3D images of 9 subjects’ faces. The images were altered to have ideal lip position and ideal convexity, ideal lip position and Class II convexity, Class II lip position and ideal convexity, and Class II lip position and Class II convexity. 400 laypersons rated their perceptions of the subjects’ athletic ability, popularity, leadership, and intelligence on a VAS scale. Subjects with ideal lip position relative to the …