Life Sciences Commons^™

Malat1 Mediates Tet2 Loss Of Function-Driven Oncogenic Inflammation Via Rna Shielding Of Nf- Kappa B P65, Nana Adjoa Ben-Crentsil

USF Tampa Graduate Theses and Dissertations

TET2 is a dioxygenase that regulates gene expression and hematopoiesis by oxidizing 5-methylcytosine residues on DNA to 5-hydroxymethylcytosine. TET2 mutations are common genetic events in hematological disorders. For example, TET2 is the most frequently mutated gene in Chronic Myelomonocytic Leukemia and occurs in about 33% of other myeloid malignancies. It is also the second commonest mutation in clonal hematopoiesis of indeterminate potential (CHIP), a common premalignant condition in the elderly. TET2 mutations arise in founding clones and are implicated in many non-hematological sequelae seen in CHIP like atherosclerotic disease, chronic liver disease, and severe microbial infections.

The development of TET2-deficient …

Heparan Sulfate Roles In Amyloid-Beta Clearance And Alzheimer’S Disease Pathogenesis, Ilayda Ozsan

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease (AD) is the most common form of dementia yet remains without an effective treatment due to its poorly understood etiology. Mounting evidence points to the accumulation and aggregation of amyloid-β peptides (Aβ), which constitute amyloid plaques in the brain, as pivotal in initiating and accelerating AD pathogenesis. Extensive efforts have focused on uncovering the molecular underpinnings and fundamental origins of impaired Aβ metabolism in AD. Heparan sulfate (HS), a linear polysaccharide of the glycosaminoglycan family, co-deposits with Aβ in plaques within the AD brain. It directly binds to and accelerates Aβ aggregation, interacts with key players in Aβ …

Overcoming Microenvironmentally Mediated Resistance In Targetable Non-Small Cell Lung Cancer, Bina Desai

USF Tampa Graduate Theses and Dissertations

The introduction of targeted therapies has resulted in immense success in treating lung cancer patients, where many patients experience long-term remission. Yet, the tumors relapse into an advanced state of disease, and ultimately, treatment failure. This can be ascribed to incomplete eradication of tumor cells by targeted therapies, which enables the residual tumor cells to propagate resistant tumors and cause subsequent relapse in patients. Therapy sensitivity is influenced not only by cell-intrinsic mechanisms but also by inputs from the stromal microenvironment. Despite widespread recognition of the stromal microenvironment's role in modulating therapy sensitivity, its contribution to therapeutic responses in vivo …

Time-Transgressive Microbial Diversity In A Tropical Bat Guano Accumulation, Deer Cave, Mulu, Borneo, Joyce Lundberg, Donald A. Mcfarlane

International Journal of Speleology

Bat guano accumulations in caves can constitute large deposits of organic material, particularly chitin and its degradation products, that host a diverse microbiome. Previous microbiological studies have not addressed the stratified nature of these deposits in the context of the timeframe of the decomposition process. We present such data (temperature, pH, DNA sampling of eight carbon-dated strata) for a 75 cm-deep tropical guano accumulation that undergoes complete decomposition over a timescale of ~120 years. The aerobic, surface layer of freshly-fallen guano has the greatest diversity of taxa, with Bacteroidota co-dominant with Pseudomonadota, and includes many taxa unique to this …

A Shield-Bearer’S Tale: Elucidating The Roles Of Estradiol And Choline In Mitigating Chemotherapy-Related Cognitive Impairment, Robert W. Botelho Jr.

USF Tampa Graduate Theses and Dissertations

Chemotherapy-Related Cognitive Impairments (CRCIs) are significant consequences of chemotherapy that affect a substantial portion of breast cancer survivors, potentially persisting long after treatment cessation. This series of studies investigated the neuroprotective roles of estradiol and choline against CRCIs induced by cyclophosphamide and doxorubicin (CYP/DOX), commonly known as Adriamycin/Cytoxan (AC) chemotherapy. Utilizing the MMTV-PyVT mouse model of breast cancer, this body of work spans several experimental studies, the first of which evaluates the impact of dietary choline supplementation on spatial memory and cholinergic function in tumor-bearing mice undergoing chemotherapy. The subsequent study tests whether impaired ovarian function and resulting reductions in …

Populations Of The Stygobiotic Amphipod Palearcticarellus Pusillus (Martynov, 1930) Maintain Genetic Connectivity Between The Mountain Springs And The Deep Bottom Habitats Of Lake Teletskoye (Altai Mountains, Russia), Ivan Marin, Liubov Yanygina, Svetlana Ostroukhova, Dmitry Palatov

International Journal of Speleology

The diversity of underground fauna is often associated with the presence of karst areas, which have extensive underground cavities and connecting channels. Non-karst areas, however, make up a larger portion of the planet’ surface, and our understanding of the distribution and dispersal abilities of underground fauna in these areas currently remains limited. During a recent study of the diversity of stygobiotic crustaceans in the mountain streams of the Kurai Mountain Range (Altai, Russia), a small-sized species of crangonyctid amphipod, Palearcticarellus pusillus (Crustacea, Amphipoda, Crangonyctidae) was found in high-altitude springs. This species has been previously known only from deep-water habitats in …

Gene Expression Analysis Reveals Dysregulation In Traumatic Brain Injury Leading To Tauopathy, Kristina M. Tosi

USF Tampa Graduate Theses and Dissertations

Traumatic Brain Injury (TBI) causes a cascade of detrimental events within neurons, contributing to a host of neurological diseases relating to dementia. In this study we have performed a meta-analysis comparing differentially expressed genes (DEG) in specific cell types such as neurons and microglia revealing inflammation as a common driver of neurological deficiencies post TBI. Inflammation and hypoxia are well characterized features of TBI; however, the molecular mechanisms causing tau hyperphosphorylation by tauopathy associated genes (TAG) post-TBI are currently poorly understood. Furthermore, there are limited in-vitro neuroinflammatory models that mimic primary and secondary TBI. We hypothesize that inducing hypoxia and …

Identification And Characterization Of Intrinsically Disordered Protein Regions, Guy Wayne Dayhoff Ii

USF Tampa Graduate Theses and Dissertations

This dissertation investigates protein intrinsic disorder and intrinsically disordered protein regions (IDPRs) through the development and application of advanced computational and experimental techniques. Chapter 1 provides an introduction to protein intrinsic disorder, outlining the historical context and fundamental concepts that highlight the importance of intrinsically disordered proteins (IDPs) and IDPRs in various biological processes. Chapter 2 focuses on the rapid prediction and analysis of protein intrinsic disorder. We introduce RIDAO (Rapid Intrinsic Disorder Analysis Online), a high-efficiency web-based tool that integrates multiple disorder predictors. RIDAO significantly outperforms existing predictors in computational efficiency, making it suitable for large-scale proteomic studies. We …

The Influence Of Recycled Water On Microbial Source Tracking Techniques That Aim To Identify Untreated Sewage In Surface Waters, Aldo E. Lobos

USF Tampa Graduate Theses and Dissertations

Fecal pollution in recreational waters can introduce pathogens that cause increased human health risk, where exposure can occur during recreational activities such as swimming, diving, surfing, and fishing. Furthermore, human fecal pollution (i.e., sewage) can introduce nutrients and other harmful chemicals that may negatively affect the environment and aquatic species. Generally, sewage is considered the highest risk to human health compared to animal fecal pollution because it typically contains a high diversity of pathogens (including human specific viruses), antibiotic resistant bacteria and genes associated with antibiotic resistance. However, pathogens are difficult to detect due to their low concentrations in the …

The Influence Of Childhood Trauma On Dna Methylation Patterns And Sex-Specific Cortisol Stress Reactivity: A Secondary Analysis, Isabella F. Correia

USF Tampa Graduate Theses and Dissertations

Childhood trauma has been shown to significantly impact physical and mental health outcomes, leading to conditions such as heart disease, diabetes, depression, and difficulties in decision-making and maintaining relationships. Exposure to such trauma has the potential to dysregulate an individual’s stress response system, resulting in abnormal cortisol levels. Many studies suggest a lasting impact of early-life stress on DNA methylation patterns and, separately, cortisol stress reactivity. In addition, there are known sex differences in exposure to childhood trauma and cortisol reactivity; yet studies to date have not investigated whether there is an association to DNA methylation. This study utilized a …

Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee

USF Tampa Graduate Theses and Dissertations

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2T61I mutation being the most widely studied. We generated the first transgenic mouse models expressing human CHCHD2WT and the PD-linked CHCHD2T61I mutation driven by the mPrP promoter. CHCHD2T61I Tg, but not CHCHD2WT Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, …

The Role Of L-Fucose In Dendritic Cell Antigen Presentation And Polarization, Chase J. Burton

USF Tampa Graduate Theses and Dissertations

Since the FDA approval of IL-2 in cancer treatment in the 1980s, immunotherapy has emerged as the standard of care for several tumor types (e.g., melanoma, lung, bladder, colorectal). However, approximately 70 percent of cancer patients, independent of prior treatment or staging, administered immunotherapy will not achieve complete responses and will exhibit disease progression. Several factors have been identified to contribute to treatment failure, including the accumulation of intratumoral immunosuppressive cell populations, insufficient tumor-infiltrating anti-tumor immune populations, or the occurrence of immunoediting on tumor cells. Current strategies to circumvent immunosuppression either lack durable response to new immunosuppressive mechanisms the tumor …

Characterization And Reprogramming Of T-Cell Metabolic Dysfunction In Chronic Lymphocytic Leukemia For Improved Adoptive Cell Therapy, Wael B. Gamal

USF Tampa Graduate Theses and Dissertations

Chronic lymphocytic leukemia (CLL) is a predominant B-cell malignancy impacting elderly populations in Western societies. Targeted therapies have revolutionized the CLL treatment landscape. Still, patients often require long-term therapy and are subject to drug-induced resistance and severe toxicities, for which CLL is still considered an incurable disease. T-cell-based immunotherapy, particularly chimeric antigen receptor (CAR) T cells, has shown remarkable success, leading to various FDA approvals in hematological malignancies. Nonetheless, CAR T-cell therapy success rate is limited in CLL because of the dysfunctional nature of T cells. CLL T cells exhibit skewing toward immunosuppressive and terminally differentiated phenotypes, leading to hindrances …

Functional Studies Of Dcaf14 In Replication Fork Stability And Genome Integrity, Neysha Tirado-Class

USF Tampa Graduate Theses and Dissertations

The response to replication stress is critical for ensuring the stability of replication forks and preserving genome integrity. To aid this response, several factors are recruited to stalled replication forks to prevent irreversible collapse of the replication machinery. Replication fork proteomic analyses of stalled forks reveal enrichment of DCAF14, a component of the Cullin4-RING (CRL4) E3 ubiquitin ligase complex, that mediates replication fork protection by blocking nuclease-mediated digestion of nascent DNA. However, little is known about the molecular mechanism by which DCAF14 functions in the context of replication stress. Notably, loss of function mutations in DCAF14 are associated with a …

Group B Streptococcus Intestinal Barrier Disruption And The Protective Role Of Butyrate, Kristen Dominguez

USF Tampa Graduate Theses and Dissertations

Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. Intrapartum antibiotics in GBS-colonized mothers significantly reduced the incidence of early-onset sepsis occurring in the first week of life; however, there are currently no prophylactic interventions for late-onset sepsis, occurring within the first 3 months of life. GBS is a pathobiont that primarily colonizes the gastrointestinal tract and can cross the intestinal barrier via both the paracellular and transcellular routes, causing invasive disease. Neonatal susceptibility to GBS intestinal translocation is mediated by inadequate epithelial barrier function and microbiome immaturity; however, the mechanisms by which GBS exploits …

Porphyrin Overdrive In Cancer: Unraveling The Mechanisms And Therapeutic Potential, Pravin D. Meshram

USF Tampa Graduate Theses and Dissertations

The increased understanding of cancer cell metabolism has shown options for novel treatment strategies. This thesis looks at the role of heme metabolism, specifically "porphyrin overdrive," in cancer progression and treatment. Cancer cells are hypermetabolic and rely on heme synthesis. When treated with δ-aminolevulinic acid (ALA), they abnormally accumulate heme intermediates. This metabolic weakness presents an opportunity to exploit heme synthesis in targeted cancer therapy. In this study, we suggest a "Bait and Kill" technique that uses exogenous ALA to induce protoporphyrin IX (PpIX) buildup in cancer cells, making them more susceptible to oxidative stress. We investigate the possibility of …

Modeling Pelagic Feeding In The Gulf Of Mexico With Implications For Ecosystem-Based Fisheries Management, Rebecca L. Scott

USF Tampa Graduate Theses and Dissertations

The focus of this dissertation was simulating trophic dynamics in the pelagic Gulf of Mexico (GOM) with an emphasis on ecosystem-based fishery management (EBFM) strategies for large pelagic species. Fisheries management in the United States largely utilizes single-species assessments, although managers are increasingly interested in EBFM approaches to better account for ecosystem effects on stocks such as predator/prey dynamics. Production in the surface layer of the pelagic zone is variable with environmental conditions and prey is often concentrated in patches by hydrodynamic features. Production is also transported vertically via diel vertical migration, during which deep-sea species provide potentially key forage …

Assessing Roman Catholics’ Modern Beliefs And Behaviors Surrounding Genetics Counseling Services, Mary S. Shinaberry

USF Tampa Graduate Theses and Dissertations

Currently, there is limited knowledge about the contemporary beliefs of Roman Catholics regarding genetic healthcare, and concerns exist that they may be less comfortable accessing genetic counseling services. To better meet the needs of this population, we interviewed 18 adult Roman Catholics living in the United States. A novel method of thematic analysis was utilized, combining traditional qualitative techniques with the assistance of ChatGPT-4, following best practices proposed to improve the trustworthiness of AI-assisted qualitative analysis. The majority of participants were college-educated women aged 25-40, none of whom had seen a genetic counselor. Most participants associated the term “genetic counseling” …

Comparing The Genomes Of Multidrug And Vancomycin-Resistant Enterococcus Faecium From A Florida Wastewater Treatment Plant, Eleanor Brodrick

USF Tampa Graduate Theses and Dissertations

Vancomycin-resistant Enterococcus (VRE) are a serious health threat, causing 50,000 infections and 5,000 deaths each year in the United States (CDC, 2019). Multidrug-resistant VRE are becoming more prevalent, and treatment options for infections caused by these organisms are limited (Arias et al., 2010; CDC, 2019). Multidrug resistant VRE have been previously isolated from wastewater in Brazil, Canada, and Portugal (Araújo et al., 2010; de_Farias et al., 2022; Sanderson et al., 2019). Thirteen vancomycin-resistant Enterococcus faecium isolated from three stages of a Florida wastewater treatment plant were fully resistant to the following antibiotics: vancomycin, ampicillin, ciprofloxacin, erythromycin, tetracycline, and nitrofurantoin, and …

Cornus Officinalis Extract Activates The Keap1/Nrf2 Pathway And Delays T1d Onset In The Nod Mouse, Justin D. Fletcher

USF Tampa Graduate Theses and Dissertations

Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of the insulin producing pancreatic β cells. The only therapeutic option following T1D clinical onset is exogenous insulin supplementation. At present, there is no cure for T1D and attempted interventional therapy has been focused on modulating the immune system. Few attempts have been pursued at preserving β cell function and survival. Here we provide a novel approach using extract from the fruit of the Cornus officinalis (CO) tree to preserve β cell function through the prevention of β cell stress. CO has been used in traditional Chinese …

Investigation Of Self-Assembly Of Hen Egg White Lysozyme Fibrils, Nabila Bushra

USF Tampa Graduate Theses and Dissertations

Amyloid proteins are a large group of proteins that tend to aggregate and form insoluble fibrils with a characteristic cross-β sheet structure. Intriguingly, this process of “amyloid formation” has been simultaneously linked to devastating human diseases called amyloidoses, ranging from Alzheimer’s Disease, cardiac amyloidoses to type II diabetes, as well as functional biological responses such as hormone storage and sperm quality control. Amyloid fibrils have also attracted significant attention for their unique mechanical, chemical, and optical characteristics, establishing them as promising tough biomaterials. The urgent need to find treatments for Alzheimer’s disease, and the demand for safe and renewable biomaterials …

The Polyaneuploid Cancer Cell State And Therapeutic Resistance: Eco-Evolutionary Dynamics In Structured Populations, Anuraag Bukkuri

USF Tampa Graduate Theses and Dissertations

In this dissertation, I develop and apply eco-evolutionary modeling techniques to understand how the polyaneuploid cancer cell (PACC) state, entered when aneuploid cells exit the cell cycle after S phase and undergo a whole genome duplication, contributes to therapeutic resistance. Since resistance remains one of the primary causes of treatment failure in cancer patients, it is critical to understand how such demographic state transitions allow for acclimatization of cancer cells to therapeutic stressors and how they interact with evolutionary processes to promote irreversible resistance.

In Chapters Two and Three, I lay the foundation for this work. In Chapter Two, I …

Macrophage-Driven Car T Cell Resistance In B Cell Lymphoma, Sae Bom Lee

USF Tampa Graduate Theses and Dissertations

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/ refractory large B cell lymphoma (LBCL). Despite its promising efficacy, a subset of patients experiences primary resistance or relapse. In Chapter 2, we explore the tumor microenvironment (TME)-induced resistance mechanisms in patients with LBCL. Analysis of the intratumoral immune infiltrates in pre-infusion tumor biopsies revealed that the levels of immunoregulatory macrophages were elevated in patients who responded poorly to axicabtagene ciloleucel (axi-cel). Using preclinical mouse B cell tumor models, we found that the CAR T-cell-produced interferon-gamma (IFN-γ) enhanced the expression of inducible nitric oxide synthase (iNOS, …

Tetr Family Regulator, Farr, Influences Rot-Mediated Control Of Virulence Factor Expression In Staphylococcus Aureus, Julia C. Schumacher

USF Tampa Graduate Theses and Dissertations

Point-mutation variants of the TetR family regulator, FarR, have emerged across Staphylococcus aureus sequence types as conferring antibiotic and fatty acid resistance, particularly in Hospital-Associated Methicillin Resistant S. aureus (HA-MRSA) strains. FarR also exhibits an additional largely uncharacterized relationship to virulence factor production, seemingly through the global repressor of toxins—Rot, which functions to regulate S. aureus’ ability to colonize and persist in the host via a complex cascade of signaling. While Rot protein is post-transcriptionally regulated by the highly characterized Agr system, there is little known about its transcriptional regulation. Herein, we explored these dynamics by initially characterizing virulence phenotypes …

Multivalency Of The Mdmx Acidic Domain Slims Use Different Binding Modes To Inhibit Mdmx And P53, Malissa Fenton

USF Tampa Graduate Theses and Dissertations

Regulation of protein binding through autoinhibition commonly occurs via interactions involving intrinsically disordered regions (IDRs). These intramolecular interactions can directly or allosterically inhibit intermolecular protein or DNA binding, regulate enzymatic activity, and control the assembly of large macromolecular complexes. Autoinhibitory interactions mediated by protein disorder are inherently transient, making their identification and characterization challenging. In this work, we explore the structural and functional diversity of disorder-mediated autoinhibition for a variety of biological mechanisms, with a focus on the role of multivalency and effective concentration. We also discuss the evolution of disordered motifs that participate in autoinhibition using examples where sequence …

Advancing Text Summarization And Classification: Deep Insights From Transformer-Based Statistical Learning, Kun Bu

USF Tampa Graduate Theses and Dissertations

Artificial Intelligence (AI) is a part of human's daily life nowadays. Machine Learning (ML) as one aspect from AI has been rapidly developing during the past two decades, especially from the statistical learning approaches, which emphasized the use of probability and statistics to model data, such as Support Vector Machines (SVMs) for classification and regression tasks to the ensemble learning techniques, such as Random Forest, Gradient Boosting Machine (GBM), and stacking. Ensemble learning has evolved into a pivotal concept in contemporary machine learning, empowering practitioners to amalgamate multiple models to enhance generalization, accuracy, and robustness. As the field of machine …

The Thermodynamics And Structure Of Tumor Suppressor P53 And Helical Mutants Binding To Inhibitors Mdm2 And Mdmx At The Primary And Secondary Sites, Pirada Serena Higbee

USF Tampa Graduate Theses and Dissertations

p53 is an intrinsically disordered protein that is a tumor suppressor. The transactivation domain is split into two parts (TAD1 and TAD2). These TADs bind to inhibitors MDM2, and a homolog, MDMX, but TAD1 binds with greater affinity. MDM2 is an E3 ubiquitin ligase that leads to the degradation of p53. MDMX is not an E3 ubiquitin ligase, but it does prevent p53 from binding to DNA, thus preventing its tumor suppressor role.

Previous research showed that increasing p53 helicity by mutating prolines to alanines increased p53's helicity but not the length of the helix. The increase in helicity increased …

Thermal Ecology And Swimming Performance Of Native Tadpoles Dryophytes Femoralis In Central Florida, Jessalyn Aretz

USF Tampa Graduate Theses and Dissertations

Urbanization and climate warming have contributed to global amphibian declines in recent decades. Amphibians are particularly vulnerable to climate and urban-induced warming because their physiological processes are dependent on temperature across all life stages, but few studies have been done on tadpole responses to warming in comparison to adult responses. The study objective was to determine how the thermal ecology and swimming performance of a native Florida tadpole varied with rearing temperature and urban level, and whether these traits are plastic or adaptive. We collected eggs from wild populations of pine woods treefrog (Dryophytes femoralis) tadpoles at an urban and …

An Analysis Of Florida Manatee (Trichechus Manatus Latirostris) Rescues (1993-2022) With Recommendations For Future Rehabilitation Program Needs, Katherine Frisch

USF Tampa Graduate Theses and Dissertations

Florida manatees (Trichechus manatus latirostris) are threatened marine mammals that inhabit the coastal and near shore waters along the southeastern United States, primarily Florida. Manatee conservation is multi-faceted. One component of the manatee recovery program is the rescue and rehabilitation program that provides care for sick, injured and orphaned manatees. The science of conservation biology, whose goal is to maintain biodiversity using a multidisciplinary approach, can be applied to aspects of the manatee rescue and rehabilitation program.

A federally authorized, state implemented, rescue system has been in place for many years to rescue and treat injured and orphaned animals. Rescued …

Effects Of Diminazene Aceturate On Drosophila Melanogaster: A Lipidomic Analysis, Gabriela Suarez

USF Tampa Graduate Theses and Dissertations

Pesticides are agents designed to eradicate living organisms to preserve agricultural needs.¹ Today the most commonly used pesticides are termed “modern pesticides”, they are characterized by lower lipophilicity and limited stability, making them less time persistent in the environment. Among these modern pesticides are organophosphorus, urea, phenoxy alkanoic, triazine, chloroacetanilide, and glyphosate-based pesticides.² The issue faced with most of these pesticides is that they affect more than just the targeted pest and pose a danger to not only humans, but also entire ecosystems.^1,3,4 While there are many different types of pesticides, insecticides show the most variance and …