Medicine and Health Sciences Commons^™

Targeting Autopalmitoylation To Modulate Protein S-Palmitoylation, Laura Dawn Hamel

USF Tampa Graduate Theses and Dissertations

Palmitoylation refers to the covalent attachment of fatty acids, such as palmitate, onto the cysteine residues of proteins. This process may subsequently alter their localization and function. Nearly all of the enzymes that catalyze palmitoylation, zDHHC protein acyl transferases (PATs), are implicated in neurological disorders, infectious diseases, and cancer in humans. Of particular interest to those who study palmitoylation are Ras family GTPas and zDHHC9-GCP16, the zDHHC PAT that palmitoylates Ras proteins. Erf2-Erf4 is the zDHHC PAT that palmitoylates Ras proteins in Saccharomyces cerevisiae. Currently, there are no methods to therapeutically target palmitoylation for the treatment of disease. One …

Molecular And Phenotypic Studies Validating The Role Of The Ecdysone Receptor In The Human Parasite Brugia Malayi, Amruta Mhashilkar

USF Tampa Graduate Theses and Dissertations

Filariasis and onchocerciasis are debilitating diseases affecting 120 million people globally. The massive socio-economic impact of these diseases energized the international community to declare a goal of eliminating filariasis 2020. This resulted in a dramatic increase in the efforts to eliminate filariasis and onchocerciasis, employing a strategy of mass drug administration (MDA). However, these programs rely upon the small arsenal of drugs. This leaves these programs vulnerable to failure in the face of developing resistance and local intolerance to the current drug regimens. Thus, new drugs against these infections are critically needed. A homologue of the ecdysone receptor (EcR), a …

Use Of Spirometry For Medical Clearance And Surveillance In Occupations Requiring Respirator Use, Ushang Prakshbhai Desai

USF Tampa Graduate Theses and Dissertations

Medical certification of workers for respirator use is an important activity of occupational medicine health professionals. Spirometry is a diagnostic tool to evaluate respiratory distress/insufficiency that may affect respirator use. In this study, we analyzed the pulmonary function data of 337 workers from different occupations which required medical evaluation to wear a respirator. The American Thoracic Society and National Fire Protection Association criteria were used to evaluate employees. Of 337 workers who were cleared for respiratory use on the basis of medical questionnaires for respirator compliance, 14 (4.15%) failed to pass respirator compliance on the basis of NFPA criteria and …

Estimating Likelihood Of Having A Brca Gene Mutation Based On Family History Of Cancers And Recommending Optimized Cancer Preventive Actions, Mehrnaz Abdollahian

USF Tampa Graduate Theses and Dissertations

BRCA1 and BRCA2 are gene mutations that drastically increase chances of developing breast and ovarian cancers, up to 20-fold, for women. A genetic blood test is used to detect BRCA mutations. Though these mutations occur in one of every 400 in the general population (excluding Ashkenazi Jewish ethnicity), they are present in most cases of hereditary breast and ovarian cancer patients. Hence, it is common practice for the physicians to require genetic testing for those that fit the rules as recommended by the National Cancer Comprehensive Network. However, data from the Myriad Laboratory, the only provider of the test until …

Basal Salivary Oxytocin And Skin To Skin Contact Among Lactating Mothers Of Premature Infants, Jessica Marie Gordon

USF Tampa Graduate Theses and Dissertations

This dissertation research explored mechanisms of human milk (HM) expulsion by describing the effects of skin to skin contact (SSC) on maternal basal oxytocin (OT) secretion among 20 premature mothers with hospitalized premature infants. This one-group, repeated measures design consisted of: 1) daily SSC with covariant data via self-report diary and 2) maternal salivary OT with and without SSC at 4 time points were collected over a 7 day time frame. Results indicate that mean levels of basal OT increase over time (M 234 pg/ml, SD 108 pg/ml time point 1; M 257 pg/ml, SD 125 pg/ml time point 3). …

Structure Based Drug Design Targeting Bacterial Antibiotic Resistance And Alzheimer's Disease, Eric Michael Lewandowski

USF Tampa Graduate Theses and Dissertations

Structure based drug design is a rapidly advancing discipline that examines how protein targets structurally interact with small molecules, or known inhibitors, and then uses this information to lead inhibitor optimization efforts. In the case of novel inhibitors, protein structural information is first obtained via X-ray crystallography, NMR studies, or a combination of both approaches. Then, computational molecular docking is often used to screen, in silico, millions of small molecules and calculate the potential interactions they may have with the target protein’s binding pocket, in hopes of identifying novel low affinity inhibitors. By examining the interactions these small, low affinity, …

The Association Of Cognitive Endophenotypes And Risky Single Nucleotide Polymorphisms Of Alzheimer's Disease Within The Alzheimer's Disease Neuroimaging Initiative (Adni) Database, Kyle Joseph Jennette

USF Tampa Graduate Theses and Dissertations

Objective: The purpose of this study was to assess the influence of three single nucleotide polymorphisms (SNP) previously associated with Alzheimer's disease on specific domains of cognition, when controlling for Apolipoprotein E gene (APOE), in a sample of individuals with Alzheimer's disease. Methods: The data were drawn from the Alzheimer's Disease Neuroimaging Initiative database, a comprehensive, longitudinal database of controls, persons with mild cognitive impairment, and persons with mild Alzheimer's disease. Each subject has a full neuropsychological assessment, neuroimaging, genetic sequencing, and physical evaluation. For the purposes of this study, individuals were selected based on the presence of the three …

Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

USF Tampa Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …

Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky

USF Tampa Graduate Theses and Dissertations

Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …

Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS, mice show abnormal behavioral …

Ikaros Deficiency Leads To An Imbalance In Effector And Regulatory T Cell Homeostasis In Murine Pancreatic Cancer, Nadine D. Nelson

USF Tampa Graduate Theses and Dissertations

Pancreatic cancer is one of the deadliest cancers with a five-year survival rate of 6%. Pancreatic cancer is resistant to conventional chemotherapy and is usually diagnosed at late stages. Current treatment options have minimal effects in extending patients' lives beyond 10 months. One significant limitation in developing treatments to combat pancreatic cancer is its immunosuppressive microenvironment. Pancreatic cancer secretes factors that activate immunosuppressive cells, such as regulatory T cells (Tregs). These Tregs suppress effector CD4⁺ and CD8⁺ T cell anti-tumor immune responses. Therefore, novel treatment options to reduce Treg-mediated immune suppression and increase the numbers and functions of …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

Assessment Of The Impact Of Attention Deficit Hyperactivity Disorder On Type 1 Diabetes, Kellee Miller

USF Tampa Graduate Theses and Dissertations

Individual day-to-day management and effective control of type 1 diabetes (T1D) is ultimately driven by decisions made by the individual. Individuals with attention deficit hyperactivity disorder (ADHD) have a higher tendency to be inattentive, impulsive, and hyperactive. Attention deficits and impulsivity among adolescents and adults with T1D could result in poor diabetes management through infrequent self-monitoring of blood glucose and inadequate insulin dosing – key components of achieving optimal glycemic control.

This study included 7,380 adolescents and young adults, ages 13-25 years, participating in the T1D Exchange clinic registry (median age 17.4 years, duration 7.7 yrs, 50% female, 81% white). …

Immunological Characterization Of Duffy Binding Protein Of Plasmodium Vivax, Miriam Thankam George

USF Tampa Graduate Theses and Dissertations

Plasmodium vivax Duffy binding protein (DBP) is an essential ligand for reticulocyte invasion making it a premier asexual blood stage vaccine candidate. However, strain-specific immunity due to DBPII allelic variation may complicate vaccine efficacy, suggesting that an effective DBPII vaccine needs to target immune responses to conserved epitopes that are potential targets of strain-transcending neutralizing immunity. Anti DBPII monoclonal antibodies, which were previously characterized by COS7 cell binding assay as inhibitory and non-inhibitory to DBPII-erythrocyte binding, were mapped to DBPII gene fragment libraries using phage display. Inhibitory mAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3 while non-inhibitory …

An Assessment Of Retractions As A Measure Of Scientific Misconduct And Impact On Public Health Risks, Alison J. Abritis

USF Tampa Graduate Theses and Dissertations

Research misconduct has been generally considered a limited issue, occurring in a small percentage of research studies. Studies of the number of article retractions use retraction percentages to perpetuate the idea that research misconduct is not a common event, and use information in the retraction notice to quantify types of research misconduct and types or research error. However, retractions appear to be the wrong variable with which to assess misconduct rates and characteristics. Using final misconduct findings in hard science research from the Office of Research Integrity (ORI) for investigations closed from 1993 through 2013, the number of publications and …

Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic

USF Tampa Graduate Theses and Dissertations

The causative agent of malignant tertian malaria, Plasmodium falciparum undergoes an arrested growth phenotype of its erythrocytic stage when under drug-stress. Recent artemisinin treatment failures seem to be indicative of such induction followed by recrudescence rather than actual therapeutic failure. Likewise, P. vivax hypnozoites are the prototypic dormants and the latent infections for which they are responsible prove most difficult to treat. Dihydroartemisinin, an artemisinin-derivative, can be used to exploit this mechanism by inducing a dormant state in ring-stage P. falciparum parasites and in turn, their recovery may be used as a screening period for compounds that inhibit or foster …

Maternal Stress, Breastmilk Igf-1, And Offspring Growth Among Breastfeeding Mothers-Infant Pairs In The Tampa Bay Area, Lauren Michelle Gottfredson

USF Tampa Graduate Theses and Dissertations

Background: Maternal stress during utero has been shown to have negative health consequences on the offspring, including low birth weight and increased risk of adult disease. Variation in breastmilk may act as an environmental cue of maternal stress and continue to program the infant during early life. This research aimed to explore the role of breastmilk on developmental programming of the infant. Specifically, to examine how breastmilk may act as a medium for the exposure of stress between the mother and the offspring, and see if variation in insulin like growth factor-1 (IGF-1) a potential mechanism for the relationship.

Methods: …

Mediation And Moderation Analysis Of Nutrition, Inflammatory Biomarkers, And Cognition In Older Adults, Elizabeth Handing

USF Tampa Graduate Theses and Dissertations

Nutrition can be viewed as a modifiable factor related to maintaining and preserving health in older adults. Previous studies have found that nutritional factors can influence cognitive abilities, however few studies have examined macronutrients and micronutrients as they relate to cognitive functioning. Research has yet to examine the mechanisms related to nutrition, cognition and aging in an older adult population from a holistic and interactive perspective.

This dissertation examined three research questions to better understand the relationship between age, nutrition, cognition, and inflammatory biomarkers. First, is nutrition related to cognition beyond demographic factors? Do individual nutrients serve as mediators? Second, …