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Off-Target Based Drug Repurposing Using Systems Pharmacology, Brent M. Kuenzi

USF Tampa Graduate Theses and Dissertations

The goal of this study was to identify novel drug repurposing opportunities in cancer by utilizing the off-target profiles of clinically relevant kinase inhibitors. This was based on the observation that the global target profiles of compounds are largely ignored and that many compounds have activity that cannot be explained by their cognate target alone. Additionally, by utilizing clinically relevant compounds, any results would hold a high potential for eventual clinical implementation. We utilized a systems pharmacology approach utilizing cell viability-based drug screening to identify compounds with beneficial off-target activity and then using chemical and phosphoproteomics in order to elucidate …

The Effects Of Gopher Tortoise (Gopherus Polyphemus) Herbivory On Plant Community Composition And Seed Germination, And The Effects Of Gut Passage On The Germinability Of Seeds: A Meta-Analysis, Jason C. Richardson

USF Tampa Graduate Theses and Dissertations

Herbivory produces direct and indirect effects on plants and at different spatial scales will have varied consequences. Consumption of plants by vertebrate grazers may affect the plants on an organismal level through direct mortality, on a community level by changing species composition or by altering the rate of succession, and even at a whole ecosystem level by altering nutrient cycles.

The majority of the scientific literature has focused extensively on herbivory by mammals and birds. With regard to mammals, studies have shown how folivory affects individual plants, plant populations, and communities of plants.

Mammals, as well as birds, also ingest …

Do All “Good Mothers” Breastfeed? How African American Mothers’ Values And Experiences Of Early Motherhood Influence Their Infant Feeding Choices, Airia S. Papadopoulos

USF Tampa Graduate Theses and Dissertations

The food an infant is fed can reflect many things: a source of nutrition, the social and cultural circumstances into which an infant is born, or even a family’s beliefs about the body and breast milk as a source of nutrition. Exclusive breastfeeding, currently the gold standard for infant feeding in the United States (US), is often identified as an expectation in discourses on being a “good mother.” African American mothers in particular are the least likely group in the US to breastfeed in any capacity and many efforts are underway to increase the breastfeeding rates of this population.

This …

Identification Of Novel Hits Against, Ala A. Azhari

USF Tampa Graduate Theses and Dissertations

Leishmaniasis is a disease caused by obligate intracellular parasites of the genus Leishmania, including 20 species that are pathogenic to humans. Female sand fly is the known vector that can transmit the disease. Visceral leishmaniasis is the severe form of the disease that affects internal organs and can be fatal with inappropriate diagnosis or treatment. Leishmania donovani is the causative agent of visceral leishmaniasis. Approximately 350 million in 89 countries are at risk of infection. Around 2 million new cases are reported annually with 500,000 of these are visceral leishmaniasis. Current drug therapies are inadequate due to their toxicity, high …

The Association Of Size Variation In The Dental Arch To Third Molar Agenesis For A Modern Population, Devin N. Williams

USF Tampa Graduate Theses and Dissertations

The frequency with which individuals do not develop their third molars, or wisdom teeth, is increasing worldwide. This current topic of human evolution is relevant to the research of anthropologists, geneticists, dentists, and other researchers involved in the study of human dentition. Many explanations have been offered to account for the prevalence of molar agenesis including, evolutionary, environmental, and genetic theories. The purpose of this research project is to determine the frequency of third molar agenesis and investigate the relationship between third molar agenesis and maxillomandibular jaw dimensions in a sample of orthodontic patients. This research tests the hypotheses that: …

Tgf-Β2 In Human Milk Research: Exploration Of A New Field Methodology And New Findings Of Biosimilar Tgf-Β2 In Non-Human Milk, Chlöe A. Sweetman

USF Tampa Graduate Theses and Dissertations

Objectives: There are three aims for this thesis: the first is to develop a field and laboratory protocol for the storage and analysis of transforming growth factor–beta 2 (TGF-β2) in human breastmilk; second, to validate this protocol and the immunoassay used to assess this new method; and lastly, to explore the ramifications of biosimilar TGF-β2 across multiple milks on human health, growth, and immunity through the review of laboratory findings and previous literature.

Rational: Little anthropological research has been done on TGF-β2 in human milk. Anthropology as a discipline is well positioned to provide insight into TGF-β2, combining biocultural, evolutionary, …

Extending Spectrophotometric Pht Measurements In Coastal And Estuarine Environments, Nora Katherine Douglas

USF Tampa Graduate Theses and Dissertations

Nearshore and estuarine environments play a vital role in the cycling of carbon, but the effects of ocean acidification in estuarine waters have not been studied as extensively as in the open ocean. One reason for this is the limitation of pH measurement capabilities in low-salinity waters. Typically, pH in these environments has been measured using potentiometric methods that are subject to uncertainties on the order of 0.01. Spectrophotometric methods for measuring pHT offer precision and accuracy superior to those of potentiometric methods. However, previous characterizations for purified sulfonephthalein indicators, used for marine spectrophotometric measurements, are not applicable to estuarine …

The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin

USF Tampa Graduate Theses and Dissertations

Chronic liver diseases, which includes alcoholic liver disease (ALD), are consistently among the top 15 leading causes of death in the United States. ALD is characterized by progression from a normal liver to fatty liver disease (hepatic steatosis), which can lead to cirrhosis, alcoholic hepatitis, and liver failure. We have identified a novel role of phosphohistidine signaling, mediated through phosphohistidine phosphatase 1 (PHPT1), in the onset of hepatic steatosis. We have identified PHPT1 as a target of selective oxidation following acute ethanol exposure as well as being downregulated following chronic ethanol exposure. We mapped the oxidative modification site and developed …

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

USF Tampa Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction to …

Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson

USF Tampa Graduate Theses and Dissertations

Elastin-like peptide (ELP) fusions promote therapeutic delivery and efficacy. Recombinant proteins, like neurotrophins, lack bioavailability, have short in vivo half-lives, and require high manufacturing costs. Fusing recombinant proteins with genetically encodable ELPs will increase bioavailability, enhance in vivo solubilization, as well as provide a cost-effective method for purification without the need for chromatography. During expression of neurotrophin-ELP (N-ELP) fusions, dense water-insoluble aggregates known as inclusion bodies (IBs) are formed. Inclusion bodies are partially and misfolded proteins that usually require denaturants like Urea for solubilization. Strong denaturants arrest ELPs stimuli-responsive property and increase unwanted aggregation, making purification difficult, yet possible. The …

A Multivariate Approach For An Improved Assessment Of Pre-Erythrocytic Stage Therapies Targeting Plasmodium Vivax And Plasmodium Falciparum, Alison E. Roth

USF Tampa Graduate Theses and Dissertations

The malaria pre-erythrocytic stages have been identified as an ideal therapeutic target, but complex in vitro models for Plasmodium vivax and Plasmodium falciparum lack the efficiency needed for rapid screening and evaluation of new vaccines and drugs, especially targeting the P. vivax hypnozoite. To address this challenge, we employed a multi-parameter approach using “omics’” to identify pre-erythrocytic targets and biomarkers, guide phenotypic therapeutic screening, and study parasite functionality with innovative bioassays using highcontent screening. Herein, we discuss three novel bioassays formatted in 384-well plate systems with utilization of commercially-available materials and application of high-content imaging for rapid bio-image analysis. To …

Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia

USF Tampa Graduate Theses and Dissertations

Mitochondria plays a crucial role in cells by maintaining energy metabolism and directing cell death mechanisms by buffering calcium (Ca²⁺ )from cytosol. Therefore, the Ca²⁺ overload of mitochondria due to the upregulated cytosolic Ca²⁺ , observed in many neurological disorders is hypothesized to be a key pathway leading to mitochondrial dysfunction and cell death. In particular, Ca²⁺ homeostasis disruptions due to Alzheimer’ s disease (AD)-causing presenilins (PS1/PS2) and oligomeric forms of β-amyloid peptides Aβ commonly found in AD patients are presumed to cause detrimental effects on the mitochondria and its ability to function properly. We begin …

Signal Detection Of Adverse Drug Reaction Using The Adverse Event Reporting System: Literature Review And Novel Methods, Minh H. Pham

USF Tampa Graduate Theses and Dissertations

One of the objectives of the U.S. Food and Drug Administration is to protect the public health through post-marketing drug safety surveillance, also known as Pharmacovigilance. An inexpensive and efficient method to inspect post-marketing drug safety is to use data mining algorithms on electronic health records to discover associations between drugs and adverse events.

The purpose of this study is two-fold. First, we review the methods and algorithms proposed in the literature for identifying association drug interactions to an adverse event and discuss their advantages and drawbacks. Second, we attempt to adapt some novel methods that have been used in …

Remote Sensing And Spatial Metrics For Quantifying Seagrass Landscape Changes: A Study On The 2011 Indian River Lagoon Florida Seagrass Die-Off Event, René Dieter Baumstark

USF Tampa Graduate Theses and Dissertations

Florida’s seagrasses are ecologically important marine environments which have suffered major degradation caused by increasing anthropogenic pressures. A 2011 seagrass die-off event caused by an algal bloom in the Florida Indian River Lagoon (IRL) was particularly severe with a majority of seagrass lost in areas such as the Banana River. An understanding of how this coastal marine environment changed is an important step toward better managing resources for conservation. Modern tools and methods provide new opportunities to study these changes at the landscape scale, a scale that informs on the larger more comprehensive state of a system. Classified satellite imagery …

Identification Of Regulatory Mirnas Associated With Ethanol-Induced Microglial Activation Using Integrated Proteomic And Transcriptomic Approaches, Brandi Jo Cook

USF Tampa Graduate Theses and Dissertations

Chronic consumption of, and acute intoxication from, alcohol can have profound effects on the functional integrity of the central nervous system (CNS). The resident immunomodulatory cells of the CNS, microglia, provide signaling factors with both pro- and anti-inflammatory effects for protection. Microglial activation ranges through a multiplex of phases, of which have yet to be defined when induced by exposure to alcohol, and how the activation impacts surrounding cells. Exposure of alcohol has been revealed to induce an immune response in microglia, which can exhibit characteristics unique to a pro-inflammatory response depending on dose and time of alcohol exposure. To …

Molecular Phylogenetics Of Floridian Boletes, Arian Farid

USF Tampa Graduate Theses and Dissertations

The boletes are macrofungi which have undergone extensive taxonomic revisions since the advent of molecular tools. To further our understanding of the boletes in peninsular Florida, we sequenced two common Floridian boletes, and analyzed them with molecular phylogenetic tools. Boletus rubricitrinus, a common Florida bolete often found in lawns under Quercus, and likely has a distribution that extends to Texas. Based on ITS and LSU sequences and morphological studies, this species belongs in the genus Pulchroboletus. As the holotype is in poor condition, an epitype is established here. A thorough description of macroscopic and microscopic features is also provided for …

Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide

USF Tampa Graduate Theses and Dissertations

Bacterial infections have posed a serious threat to the public health due to the significant rise of the infections caused by antibiotic-resistant bacteria. There has been considerable interest in the development of antimicrobial agents which mimic the natural HDPs, and among them biodegradable polymers are newly discovered drug candidates with ease of synthesis and low manufacture cost compared to synthetic host defense peptides. Herein, we present the synthesis of biocompatible and biodegradable polymers including polycarbonate polymers, unimolecular micelle hyperbranched polymers and dendrimers that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. The developed amphiphilic polycarbonates are highly …

Comparison Of Thermal Glove Wrist-Hand Orthoses In Their Effectiveness On Rheumatoid Arthritis, Brittany E. Mott

USF Tampa Graduate Theses and Dissertations

Rheumatoid arthritis (RA) is an autoimmune disease affecting nearly 1% of the world’s population with symptoms such as inflammation, pain, and reduced strength [1]. Physicians and scientists work to develop pharmaceuticals and medical devices aimed at decreasing the symptoms associated with RA to better the lives of those affected. One of the most recent developments is the addition of thermal therapy gloves to the array of upper limb orthoses available to patients with RA. It was hypothesized that this study will show that orthoses in the form of thermal therapy gloves are beneficial to the patients by reducing symptoms such …

Food Insecurity And Age Of Menarche: Using A Biocultural Approach And Life History Theory To Assess Risks Of Food Insecurity Among Girls In Tampa Bay, Fl, Mecca Burris

USF Tampa Graduate Theses and Dissertations

Using life-history theory within a biocultural perspective, this research explores whether household food insecurity correlates with early or delayed menarche among adolescent females in Tampa Bay, Florida. Early onset of puberty and menstruation is connected with numerous health consequences including growth stunting, obesity, type-2 diabetes, adult-onset asthma, reproductive cancers, increased risk for depression, behavioral problems, and early sexual activity which increases the risk for STIs and ovarian cancer. Early menarche also seems to disproportionally impact disadvantaged and minority groups. While there are many known factors that influence age at menarche (e.g.: genetics, diet), little is understood regarding the effect of …

Grooming Behaviors Of, Lauren N. Williams

USF Tampa Graduate Theses and Dissertations

The giant freshwater shrimp, Macrobrachium rosenbergii is a large species of prawn grown extensively in aquaculture settings. A social hierarchy exists within the males of this species, representing three distinct male morphotypes. These male morphotypes differ in their behavior, physiology, and morphology and include the largest blue-clawed males (BC males), moderately- sized orange-clawed males (OC males), and the undifferentiated small-clawed males (SM males). All individuals of this species perform grooming behaviors to rid themselves of body fouling which can impede important functions such as movement, respiration, chemoreception, and reproduction. Grooming behaviors in crustaceans often utilize specialized structures called setae, which …

Ecosystem Function And Phenotypic Variation In Spartina Alterniflora Salt Marshes, Sandra E. Voors

USF Tampa Graduate Theses and Dissertations

Biodiversity is important to ecosystem function at many scales, and variation functional traits within a species can potentially influence ecosystem functioning by altering nutrient cycling dynamics. High population extinction rates are resulting in a rapid loss of within-species biodiversity, so there is a need to better understand the importance of intraspecific variation to ecosystem-level processes. Tidal salt marshes are ideal ecosystems for investigating intraspecific variation in plant-nutrient relationships because they are dominated by a monoculture of the foundation species Spartina alterniflora, with distinct phenotypes that correspond to environmental gradients across the marsh. We conducted a field survey of existing …

Sublethal Effects Of Crude Oil And Chemical Dispersant On The Eastern Oyster (Crassostrea Virginica) At Multiple Life History Stages, Sara Marie Garcia

USF Tampa Graduate Theses and Dissertations

Oil spills in the marine environment can threaten vulnerable ecosystems that support ecologically and economically significant organisms, such as the eastern oyster (Crassostrea virginica), in coastal habitats. The use of chemical dispersant (Corexit 9500) was applied as a cleanup effort in response to the Deepwater Horizon blowout to minimize crude oil slicks, but also resulted in increased concentrations of polycyclic aromatic hydrocarbons in the water column. The effects of increased soluble fractions of crude oil and dispersant components may be harmful to marine organisms. This study aimed to investigate possible sublethal impacts to the eastern oyster at multiple life history …

Developing Motion Platform Dynamics For Studying Biomechanical Responses During Exercise For Human Spaceflight Applications, Kaitlin Lostroscio

USF Tampa Graduate Theses and Dissertations

In future human spaceflight missions, with prolonged exposure to microgravity, resistive and aerobic exercises will be countermeasures for bone loss, muscle loss, and decreased aerobic capacity. Two of the exercises of interest are squats and rowing. The cyclic forces produced during these exercises are at relatively low frequencies which are likely to excite structural resonances of space vehicles. Vibration Isolation Systems (VIS) are being designed to be paired with future exploration exercise devices in order to prevent these cyclic exercise forces from impacting the space vehicle. The VIS may be configured such that a platform supports the human and exercise …

Flames And Frogs – The Impact Of Environmental Disturbances On Host-Parasite Dynamics, Nicole Ortega

USF Tampa Graduate Theses and Dissertations

The successful completion of this work is dedicated first to my grandparents for having always shown their unwavering love and encouragement in my journeys (most of which they kindly and politely only pretended to understand) and for having also served as life-long role models who upheld an unparalleled work ethic. To many whom I consider to be my chosen family, especially Ann Williams and Brittany Sears, who kept me laughing, but more importantly, kept my crazy train from derailing during these tumultuous years. To Wayne Price and Tom Jackman, who fostered the success of my career and are the epitome …

Angiostrongylus Cantonensis: Epidemiologic Review, Location-Specific Habitat Modelling, And Surveillance In Hillsborough County, Florida, U.S.A., Brad Christian Perich

USF Tampa Graduate Theses and Dissertations

Angiostrongylus cantonensis is a parasitic nematode endemic to tropical and subtropical regions and is the leading cause of human eosinophilic meningitis. The parasite is commonly known as rat lungworm because the primary host in its lifecycle is the rat. A clinical overview of rat lungworm infection is presented, followed by a literature review of rat lungworm epidemiology, risk factors, and surveillance projects. Data collected from previous snail surveys in Florida was considered alongside elevation, population per square kilometer, median household income by zip code territory, and normalized difference vegetation index specific to the geographic coordinates from which the snail samples …

Novel Role Of Histone Deacetylase 11 (Hdac11) In Regulating Normal And Malignant Hematopoiesis, Jie Chen

USF Tampa Graduate Theses and Dissertations

During hematopoiesis, multilineage progenitor cells and the precursors are committed to individual hematopoietic lineages. In normal myelopoiesis, the immature myeloid cells (IMCs) differentiate into macrophages, neutrophils or dendritic cells. However, under tumor burden, these IMCs differentiate into myeloid derived suppressor cells (MDSCs) result in an up-regulation of immune suppressive factors and pro-tumor effect. The development of normal or malignant is tightly controlled by endogenous signals such as transcription factors and epigenetic regulations. HDAC11 is the newest identified members of the histone deacetylase (HDAC) family. Previous study in our group had identified HDAC11 as a negative regulator of interleukin 10 (IL-10) …

Characterization Of The Transcriptional Elongation Factor Ell3 In B Cells And Its Role In B-Cell Lymphoma Proliferation And Survival, Lou-Ella M.M. Alexander

USF Tampa Graduate Theses and Dissertations

The studies presented in this dissertation establish the dynamics of Eleven nineteen Lysine-rich leukemia (ELL) family of elongation factors during B cell differentiation and provide a description of ELL3 function in B cells.

The transition from a mature naïve B cells into an activated B cell is dependent on a large increase in transcriptional output, which is followed by focused expression on secreted immunoglobulin upon terminal differentiation into plasma cell. While ELL family members have previously been implicated in alternative splicing at the immunoglobulin heavy chain locus in plasma cells, their presence and function prior to differentiation is currently not …