Life Sciences Commons^™

A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer

USF Tampa Graduate Theses and Dissertations

Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …

Geoarchaeology Of Estuarine Seascapes In Tampa Bay, Florida., Kendal R. Jackson

USF Tampa Graduate Theses and Dissertations

This dissertation investigates the geological, ecological, and archaeological histories of Tampa Bay, Florida’s largest open-water estuary system. Previous geoscientific and archaeological work has studied the evolution of Florida’s estuaries as ‘pre-anthropogenic’ ecosystems and conceptualized Indigenous maritime societies as mostly passive inhabitants of dynamic ‘natural’ environments. Further, the environmental legacies of more recent, industrial-scale estuary modification attending Florida’s 20th-century population boom have been understudied—leading to popular and scientific confusion about historical conditions. The work composing this dissertation research seeks to reconceptualize Tampa Bay as a complex mosaic of cultural seascapes that have been variously altered and modified by human societies across …

Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan

USF Tampa Graduate Theses and Dissertations

Background: Traumatic Brain Injury (TBI) is a major contributor to death and disability due to motorvehicle accidents, sports, physical abuse, and battlefield injuries. The primary insult to the brain leads to inflammation, vascular dysfunction, and oxidative stress in the brain as well as in the eye. This leads to loss of Retinal Ganglion Cells (RGCs) and downregulation of Brain derived Neurotopic Factor (BDNF). BDNF is a neurotrophic factor that binds to Tropomyosin Receptor Kinase B (TrkB) receptor to promote cell growth, survival, and differentiation. Current treatment strategies do not promote neuronal regeneration. Therefore, novel treatments are needed to restore vision …

A Forward Genetic Screen Identifies Genes Involved In Gametocyte Development Of The Human Malaria Parasite Plasmodium Falciparum., Jyotsna Chawla

USF Tampa Graduate Theses and Dissertations

Transmission of the deadly malaria parasite Plasmodium falciparum from human to mosquito is achieved by specialized intraerythrocytic sexual forms called gametocytes. Circulating in the vertebrate host, relatively few intraerythrocytic gametocytes are picked up during a bloodmeal to continue sexual development in the mosquito vector. Human-to-vector transmission thus represents an infection bottleneck in the parasite's life cycle for therapeutic interventions to prevent malaria. Though the crucial regulatory mechanisms leading to gametocyte commitment have recently come to light, networks of genes that control sexual development remain to be elucidated. Here, we report a forward genetic approach to identify genes associated with gametocyte …

Evaluating Foot-Drop Interventions For Multiple Sclerosis Using A Multimodal System, Laura Marie Byrnes-Blanco

USF Tampa Graduate Theses and Dissertations

This dissertation explores how multimodal walking impacts quantitative and qualitative aspects of gait for persons with multiple sclerosis (pwMS) experiencing foot-drop. Foot-drop can dramatically impede mobility and clinicians routinely prescribe ankle-foot-orthosis (AFO) and functional electrical stimulation (FES) devices to alleviate its impacts on daily life. However, little is known about how these devices affect pwMS while traversing environments with real-world complexity. To explore this topic, an interventional, parallel assigned study was conducted. A realistic nature pathway containing changes in floor pitch, audiovisual stimulation, and during-trial tasks (for dual-tasking) was generated in an immersive virtual reality system called CAREN: Computer Assisted …

Statistical Analysis Of Ribonucleotide Incorporation In Human Cells, Tejasvi Channagiri

USF Tampa Graduate Theses and Dissertations

During the DNA replication process, ribonucleotides, the building blocks of RNA, may be occasionally incorporated in the newly synthesized DNA. DNA is primarily composed of deoxyribonucleotides and there exist cellular mechanisms for removing ribonucleotides from DNA, which may point towards ribonucleotide incorporation being a replication error. Further, an excess of these ribonucleotides in the genome has been known to lead to genomic instability and has been implicated in human diseases. However, there are also hypotheses that suggest that ribonucleotides may be beneficial in certain circumstances. In this study we examine ribonucleotide incorporation in the human genome in several human cell …

Partial Characterization Of Plasmodium Falciparum Genes Implicated In Altered Artemisinin Stress Response, Caroline F. Simmons

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic illness caused by the Plasmodium spp., with an estimated 247 million malaria cases reported in 2021 across 84 endemic countries. Treatment of the deadliest malaria parasite, P. falciparum, relies on artemisinin combination therapies (ACTs). However, while ACTs have greatly decreased malaria mortality, this progress is threatened due to artemisinin (ART) partial resistance and ACT failure in Southeast Asia and Sub-Saharan Africa. SNPs to the Kelch13 (K13) gene are a well-characterized marker for ART resistance. However, increasing evidence that resistance to ART mediated by genes not related to K13 SNPs prompts the need to characterize other novel …

How Some Arboreal Salamanders (Genus Aneides) Jump, Glide, And Generate Lift, Christian E. Brown

USF Tampa Graduate Theses and Dissertations

The jumping and subsequent aerial behaviors of arboreal lungless salamanders (genus Aneides) had never been investigated or described. The aims of this research were to (1) compare jumping performance within the family Plethodontidae with a special focus on arboreal species from genus Aneides, (2) describe the biomechanics and kinematics of aerial behaviors after a jump or extended fall, and (3) model airflow over the morphology of the most aerially adept salamanders to investigate if they are capable of generating lift. First, I recorded salamanders jumping, locomoting vertically, dropping, and flying in a vertical wind tunnel. Then, I laser-scanned and reconstructed …

The Role Of The Dna Helicase Rrm3 Under Replication Stress, Julius Muellner

USF Tampa Graduate Theses and Dissertations

DNA replication needs to be strictly monitored to ensure proper duplication of the genome. During DNA synthesis, the DNA replication machinery encounters multiple obstacles such as incorrect dNTP incorporation, RNA-DNA hybrids, modification of DNA nucleobases, collision with the transcription-replication machinery. These endogenous and exogenous sources of DNA damage may result in single-strand breaks (SSBs) and double-strand DNA breaks (DSBs), thereby impeding fork progression. To prevent stalling of DNA synthesis a multitude of DNA repair pathways are specifically designed to deal with these kinds of blockages. One of the proteins involved in ensuring DNA replication fork progression is the DNA helicase …

Diet And Salivary Microbiome On Cardiovascular Risk And Glycemic Control In Participants With And Without Type 1 Diabetes: The Cacti Study, Tiantian Pang

USF Tampa Graduate Theses and Dissertations

Introduction: The prevalence of type 1 diabetes mellitus (T1DM) has been increasing drastically in the United States. People with T1DM are at a higher risk of developing diabetes-related complications, including cardiovascular disease (CVD). Diet is one of the most modifiable factors and healthy eating could reduce CVD risk among individuals with T1DM. The current 2015-2020 Dietary Guidelines for Americans focus on overall healthy eating patterns rather than individual foods and nutrients. A healthy dietary pattern or high-quality diet can be measured by diet quality indexes, and generally contains minimal ultra-processed foods (UPF). Although substantial evidence has linked poor diet quality …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Coastal Cities In The Southern Us Floodplains: An Evaluation Of Environmental Equity Of Flood Hazards And Social Vulnerabilities, Lubana Tasnim Mazumder

USF Tampa Graduate Theses and Dissertations

Floods are recognized as one of the most common and widespread natural hazards in the United States (US). They are responsible for uncompensated losses and damages. Furthermore, evidence suggests flooding inflicts more harm among socially vulnerable groups, incapable of withstanding hazard events, raising environmental equity (EE) and justice (EJ) concerns. Regrettably, with continuing climate change and urbanization, flooding will not subside in the future; instead, the flooding frequency and intensity will increase in many parts of the US, and the trend of disproportionate impacts will continue to rise.

Since Hurricane Katrina, a considerable amount of research has been conducted on …

Human Spacesuit Interaction During Eva Of The Legs Using A Force Sensing System, Niraliben D. Patel

USF Tampa Graduate Theses and Dissertations

Astronauts perform a multitude of tasks in space, both in the spacecraft and outside of the spacecraft. Extravehicular Activity (EVA) refers to any activity that is completed outside of the spacecraft, whether it is work on the actual spacecraft, spacewalks, or conducting sample collections on other planets and moons. To do this safely, a pressurized Extravehicular Mobility Unit (EMU) or commonly known as the spacesuit is used. There have been multiple iterations of the United States EMU with advances to further optimize the astronaut safety and EVA tasks. However, there is still relatively little information on the movement of the …

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

Needs Assessment For A Web-Based Support Resource For Patients With A Pathogenic Variant In Lmna, Dylan M. Allen

USF Tampa Graduate Theses and Dissertations

Pathogenic variants (PV) in the gene LMNA cause autosomal dominant inherited “laminopathies” that can affect multiple different organs, most specifically the heart. Current resources for LMNA patients are sparse and disjointed, leaving a need for a comprehensive resource catering to the wants and needs of the patients. A needs assessment of LMNA support resources was completed through reviewing published literature and existing support resources and conducting 11 semi-structured interviews with individuals who have a PV in LMNA. The Social Support Theoretical Model and thematic analysis of interview transcripts were used to identify discrepancies between the support that affected individuals receive …

Healthcare Decision Makers' Perspectives On Barriers And Facilitators To Hiring Genetic Counselors In Huntington Disease (Hd) Clinic Settings, Bailey Hummel

USF Tampa Graduate Theses and Dissertations

Huntington disease (HD) is a hereditary, neurodegenerative autosomal dominant disorder for which there are currently no effective options to prevent the onset of symptoms. Although meeting with a genetic counselor (GC) is recommended as part of national guidelines for predictive HD genetic testing and a GC is required for Centers of Excellence, not all HD centers have hired a GC. To explore drivers for, valued outcomes of, and barriers to the creation of GC positions in clinics that treat patients with HD, we conducted semi-structured interviews with 11 individuals involved with HD clinics and/or hiring decisions at 8 clinics across …

Piloting A Spanish-Language Web-Based Tool For Hereditary Cancer Genetic Testing, Gretter Manso

USF Tampa Graduate Theses and Dissertations

Cancer genetic services (including genetic counseling and testing) help identify patients and families at increased risk of developing cancer so that steps can be taken to reduce risks or find cancers early. Receipt of genetic services in the Hispanic/Latinx population is low due, in part, to a shortage of Spanish-speaking genetic counselors. To address this concern, a 12-minute online tool designed to inform individuals about cancer genetic services was translated into Spanish. The objectives of this pilot study were to determine if the educational tool improves knowledge and informed decision making and to assess usability and appropriateness of the tool …

Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling, David A. Cline

USF Tampa Graduate Theses and Dissertations

Genetic Counseling relies on communication skills to help patients understand and adapt to a genetic disease or risk. However, little is known about which skills are most commonly used or the extent to which genetic counseling sessions vary. A novel process measure titled the "Genetic Counseling Skills Checklist" (GCSC) was developed in a prior pilot study and includes 8 broad categories each consisting of 5-8 skills. This study is the first to apply the final GCSC to characterize 20 mock prenatal sessions conducted by 5 genetic counselors (GCs) for 2 prenatal indications using 3 trained actors as patients. Two experienced …

Comparing Mortality In Response To Simulated Climate Change In The Harvester Ant, Pogonomyrmex Badius, And The Fire Ant, Solenopsis Invicta, Haley Depner

USF Tampa Graduate Theses and Dissertations

With the rapid transport of plants, produce, and goods out of its South American home, the fire ant, Solenopsis invicta, has invaded continents on a global scale. In the United States alone, S. invicta is responsible for an estimated $1 billion in damages annually. In contrast to the invasive fire ant, Florida’s native harvester ant, Pogonomyrmex badius, is a keystone seed disperser, providing seed relocation benefits to Florida’s sandhill wildfire-adapted habitats. Seed relocation reduces seedling competition for nutrients with the parent plant, reduces predation of seeds by rodents, increases nutrient loads associated with ant mound soils, and protects seeds from …

Identifying Barriers And Facilitators To Family Communication Regarding Genetic Testing For Hereditary Cancer, Andrea K. Shields

USF Tampa Graduate Theses and Dissertations

Cascade testing, whereby at-risk family members are tested for known pathogenic or likely pathogenic (P/LP) variants in high risk cancer genes, provides the opportunity for changes in medical management (e.g., increased surveillance to detect cancer early or preventative surgery to reduce cancer risk). However, the rates of cascade testing are low which suggests that one-time communication may be insufficient to prompt action among family, and an increase in understanding of how to promote ongoing communication about genetic testing within families is needed. We surveyed individuals with P/LP variants in inherited cancer genes and conducted multiple linear regression with forward analysis …

Ecohydrology, Cultural Perceptions, And Recovery Of Freshwater Wetlands In A Heavily Managed Urban Aquifer, Jessica Ashley Balerna

USF Tampa Graduate Theses and Dissertations

Freshwater wetlands provide essential ecosystem services that influence, and are influenced by, human perceptions and behaviors. I explore these feedbacks in the Tampa Bay region, which hosts numerous freshwater wetlands subjected to population increases, economic growth, and shifting management policies. These wetlands are embedded in urban and residential areas, where people can observe and respond to changes in wetland condition over time. I utilized long-term (1991–2018), high sample size (n=152) datasets to assess how wetland inundation responds to the interactive effects of climate variation and shifts in water conservation policies primarily related to cutbacks in groundwater extraction. As wetland ecosystem …

Evaluation Of A Story-Telling Approach To Educate Minority Populations About Inherited Cancer, Celestyn B. Angot

USF Tampa Graduate Theses and Dissertations

Utilization of hereditary cancer genetic counseling and testing services is substantially lower among minority populations compared to white populations due, in part, to lower levels of awareness and knowledge. To help improve awareness, we designed a 7-minute video that uses storytelling to translate knowledge of genetic testing and hereditary cancer to individuals who have a personal history or family history of cancer. Consented participants were asked baseline questions about hereditary cancer and genetic testing, reviewed the video, and provided feedback on its content, understandability, and visual appeal during semi-structured interviews. Data were coded and analyzed to identify themes and determine …

Diatom Diversity And Functional Groups In 72 Florida Lakes: Assessing Ecological Changes For Improved Protection And Management, Francesca M. Lauterman

USF Tampa Graduate Theses and Dissertations

Florida lakes are diverse ecosystems and are an important part of the state's biodiversity and ecosystem services. As human population and development increase across the state, many lakes have been documented as nutrient impaired and are unable to maintain essential ecological functions. In this study, diatom diversity and functional groups in 72 Florida lakes were assessed for their relationships with associated water-quality data. Common alpha diversity indices, including Shannon-Weiner Index, the Gini-Simpson Index, and Hill’s numbers were utilized to measure trends in diatom communities, while the relationships between diatom lifeform characteristics and environmental data were explored using multivariate methods and …

Plastic Accumulation In Stormwater Pond Soils Across Socioeconomic And Watershed Development Gradients, Carley Defillips

USF Tampa Graduate Theses and Dissertations

Stormwater runoff is a major vector transporting pollution along the land-to-sea continuum, with the mobilization of nutrient pollution in stormwater runoff being well documented. Although plastic is a pollutant of growing concern, few studies have focused on the potential role stormwater ponds play in mediating plastic transport. This study uses a combination of watershed development and socioeconomic variables to characterize plastic pollution patterns in dry stormwater ponds (those not inundated outside of times of major rainfall) at a watershed scale. Each pond basin was sampled for plastics embedded in the soil and laying on the pond surface using a systematic …

Why The Delay In Recognizing Terrestrial Obligate Cave Species In The Tropics?, Francis G. Howarth

International Journal of Speleology

“Nothing could possibly live there!” They believed. Indeed, until recently, few specialized cave- adapted animals were known from volcanic, tropical, or oceanic island caves, and plausible theories had been put forward to explain their absence. But assume nothing in science! One must illuminate, explore, and survey habitats before declaring them barren. Our understanding of cave biology changed dramatically about 50 years ago following the serendipitous discovery of cave-adapted terrestrial arthropods in Brazil and on the young oceanic islands of the Galápagos and Hawai‘i. These discoveries and subsequent studies on the evolutionary ecology of cave animals have revealed a remarkable hidden …

Utilizing Neoantigen-Specific Cd4* T Cells And Immune Checkpoint Modulation To Advance Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes For Metastatic Melanoma Patients, Maclean Scott Hall

USF Tampa Graduate Theses and Dissertations

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for patients with advanced solid tumors. Metastatic melanoma is a tumor type amenable to immunotherapy in part due to the presence of antigen-specific TIL. These T cells can be activated and expanded for ACT, which has resulted in relatively high rates of clinical responses. While numerous advances have been made, the inclusion of neoantigen-specific CD4+ T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. Similarly, immune checkpoint inhibitors, specifically PD-1 blocking antibodies, augment antitumor immunity and may improve the outcomes …

Dcaf14 Regulates Cdt2 To Promote Set8-Dependent Replication Fork Protection, Neysha Tirado-Class, Caitlin Hathaway, Anthony Nelligan, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4–RING E3 ubiquitin ligase (CRL4) complexes. CDT2 is responsible for PCNA-coupled proteolysis of substrates CDT1, p21, and SET8 during S-phase of cell cycle. DCAF14 functions at stalled replication forks to promote genome stability, but the mechanism is unknown. We find that DCAF14 mediates replication fork protection by regulating CRL4CDT2 activity. Absence of DCAF14 causes increased proteasomal degradation of CDT2 substrates. When forks are challenged with replication stress, increased CDT2 function causes stalled fork collapse and impairs fork recovery in DCAF14-deficient conditions. We further show that stalled fork protection …

Otud5 Limits Replication Fork Instability By Organizing Chromatin Remodelers, Angelo De Vivo, Hongseon Song, Yujin Lee, Neysha Tirado-Class, Anthony Sanchez, Sandy D. Westerheide, Huzefa Dungrawala, Younghoon Kee

Molecular Biosciences Faculty Publications

Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts is crucial in preserving the integrity of replication forks. Various chromatin remodelers, such as histone chaperone and histone deacetylases are known to modulate replication stress, but how these factors are organized or collaborate are not well understood. Here we found a new role of the OTUD5 deubiquitinase in limiting replication stress. We found that OTUD5 is recruited to replication forks, and its depletion causes replication fork stress. Through its C-terminal disordered tail, OTUD5 assembles a complex containing FACT, HDAC1 and HDAC2 at replication forks. A …

The Identification Of Two M20b Family Peptidases Required For Full Virulence In Staphylococcus Aureus, Nathanial James Torres, Devon Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey Neil Shaw

Molecular Biosciences Faculty Publications

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival …

Upper Crustal Structure Of Superfast-Spread Oceanic Crust Exposed At The Pito Deep Rift: Implications For Seafloor Spreading, J. A. Karson, L. A. Chutas, N. W. Hayman, R. N. Hey, A. J. Horst, S. D. Hurst, E. M. Klein, D. F. Naar, R. J. Varga

Marine Science Faculty Publications

A tectonic window into the upper 2,000 m of oceanic crust generated at the superfast spreading (∼142 mm/yr) southern East Pacific Rise exposes a continuous layered structure of basaltic lavas and sheeted dikes over gabbroic rocks. This relatively simple structure is in accord with expectations for crustal accretion at a very fast spreading rate and high magma budget where magmatic construction keeps pace with plate separation. Detailed observations show that basaltic lava flows dip progressively more steeply inward (toward the spreading axis where they were erupted). Underlying sheeted dikes are faulted and tectonically rotated to dip steeply outward. These structures …