Medicine and Health Sciences Commons^™

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 …

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish

Theses and Dissertations

High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a …

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 …

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

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, …