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Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell Nov 2017

Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell

USF Tampa Graduate Theses and Dissertations

The heat shock response (HSR) is a robust cellular reaction to mitigate protein damage from heat and other challenges to the proteome. This protective molecular program in humans is controlled by heat shock transcription factor 1 (HSF1). Activation of HSF1 leads to the induction of an array of cytoprotective genes, many of which code for chaperones. These chaperones, known as heat shock proteins (HSPs), are responsible for maintaining the functional integrity of the proteome. HSPs achieve this by promoting proper folding and assembly of nascent proteins, refolding denatured proteins, and processing for degradation proteins and aggregates which cannot be returned …


Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner Nov 2017

Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner

USF Tampa Graduate Theses and Dissertations

Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the …


Glomerular Hyperfiltration And Hypertension In Diabetes, Jie Zhang Nov 2017

Glomerular Hyperfiltration And Hypertension In Diabetes, Jie Zhang

USF Tampa Graduate Theses and Dissertations

In the present study, we investigated the pathophysiological mechanisms of the hemodynamic alteration in diabetes. Glomerular hyperfiltration occurs in the early stage of diabetes mellitus and has been recognized to promote the pathogenesis of diabetic nephropathy. We determine the role of TGF response and the vascular tone of Af-Art in diabetic hyperfiltration and we found that 1) tubular high glucose directly activates NOS1 and increases NO generation in the macula densa, which inhibits TGF response and increases GFR; 2) high glucose dilates renal Af-Art through GLUT1 and mediated by NOS3-derived NO generation; 3) in diabetes, blunted TGF mediated by NOS1 …


18f-Fdg Pet/Ctct-Based Radiomics For The Prediction Of Radiochemotherapy Treatment Outcomes Of Cervical Cancer, Badereldeen Abdulmajeed Altazi Nov 2017

18f-Fdg Pet/Ctct-Based Radiomics For The Prediction Of Radiochemotherapy Treatment Outcomes Of Cervical Cancer, Badereldeen Abdulmajeed Altazi

USF Tampa Graduate Theses and Dissertations

Cervical cancer remains the third most commonly diagnosed gynecological malignancy in the United States and throughout the world despite being potentially preventable. Patients diagnosed with cervical cancer may develop local recurrence in the cervix and surrounding structures (vaginal apex, parametrial, or paracervical), regional recurrence in pelvic lymph nodes, distant metastasis, or a combination of all. The management of such treatment outcomes has not been subject to rigorous investigation. Therefore, there is a need for studies and clinical trials that focus on decision making to support the choice of the best treatment modality that leads to the minimal number of adverse …


Investigations Into The Non-Mevalonate Isoprenoid Biosynthesis Pathway's First Two Enzymes Utilizing Hybrid Qm/Mm Techniques, Justin K. White Nov 2017

Investigations Into The Non-Mevalonate Isoprenoid Biosynthesis Pathway's First Two Enzymes Utilizing Hybrid Qm/Mm Techniques, Justin K. White

USF Tampa Graduate Theses and Dissertations

Molecular drug design begins with the identication of a problem to solve. This work identies the growing resistance among human pathogens to current treatments. Once the problem is identied and understood, solutions must be proposed. This one is straight forward, we need new antimicrobial drugs. More specically, we need to identify novel targets to inhibit. A large portion of antibiotics focus on disruption of macromolecular production while only a few target metabolic systems. Finally, you need to propose solutions based on the information gathered. In order to avoid existing resistance, it is important to avoid the macromolecular route and focus …


A Historical Assessment Of Asbestos Exposure, Abatement Methods And Containment Efficacy During Asbestos Containing Material Removal Activities At A Large Federal Facility, Daniel A. Newfang Nov 2017

A Historical Assessment Of Asbestos Exposure, Abatement Methods And Containment Efficacy During Asbestos Containing Material Removal Activities At A Large Federal Facility, Daniel A. Newfang

USF Tampa Graduate Theses and Dissertations

Asbestos sampling and monitoring data, starting from 2003, located in a large federal facility’s Asbestos Air Database Management (AADM) repository will be queried and analyzed on airborne asbestos fiber concentrations generated from abatement activities of asbestos-containing materials (ACM) and asbestos-containing building materials (ACBM). Historically, concerns expressed by personnel outside of the containment areas, whether adjacent to or quite a distance from the asbestos abatement activities present operational challenges for the project manager, potential angst and uneasiness to personnel residing next to the abatement activity as well as programmatic concerns to the building/facility managers. The concerned individuals working outside the abatement …


Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose Nov 2017

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …


Ecological Epigenetics Of Avian Range Expansions, Holly J. Kilvitis Nov 2017

Ecological Epigenetics Of Avian Range Expansions, Holly J. Kilvitis

USF Tampa Graduate Theses and Dissertations

In light of human-mediated environmental change, a fundamental goal for biologists is to determine which phenotypic characteristics enable some individuals, populations or species to be more adept at coping with such change, while rendering others more vulnerable. Studying ongoing range expansions provide a unique opportunity to address this question by allowing documentation of how novel environments shape phenotypic variation on ecological timescales. At range-edges, individuals are exposed to strong selective pressures and population genetic challenges (e.g. bottlenecks and/or founder effects), which make genetic adaptation difficult. Nevertheless, certain species, such as the house sparrow (Passer domesticus), seem to thrive in their …


Design And Synthesis Of Cpg-Lytic Peptide Conjugate, Brachytherapy Beads And A Combinatorial Library Of Primary Amines Used As Potential Therapeutics In The Treatment Of Cancers, Josanne-Dee Woodroffe Nov 2017

Design And Synthesis Of Cpg-Lytic Peptide Conjugate, Brachytherapy Beads And A Combinatorial Library Of Primary Amines Used As Potential Therapeutics In The Treatment Of Cancers, Josanne-Dee Woodroffe

USF Tampa Graduate Theses and Dissertations

Cancer remains one of the most feared diseases affecting the modern world. Second to heart disease, it is the largest cause of deaths, affecting one in three persons. Cancer cells are formed when normal, healthy cells become damage, losing their normal regulatory mechanism that control cell growth. There are many different types and progression of these cancer cells that determine the type of treatment a patient receives. The primary focus of this dissertation is to propose three studies of anticancer agents. In Chapter one, a CpG-lytic peptide conjugate was designed to target receptors on the cell membrane to concentrate the …


The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler Nov 2017

The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler

USF Tampa Graduate Theses and Dissertations

Genome instability is a hallmark of human cancers. Patients with Bloom’s syndrome, a rare chromosome breakage syndrome caused by inactivation of the RecQ helicase BLM, result in phenotypes associated with accelerated aging and develop cancer at a very young age. Patients with Bloom’s syndrome exhibit hyper-recombination, but the role of BLM and increased genomic instability is not fully characterized. Sgs1, the only member of the RecQ family of DNA helicases in Saccharomyces cerevisiae, is known to act both in early and late stages of homology-dependent repair of DNA damage. Exo1, a 5′–3′ exonuclease, first discovered to play a role …


Rehabilitating Asymmetric Gait Using Asymmetry, Tyagi Ramakrishnan Nov 2017

Rehabilitating Asymmetric Gait Using Asymmetry, Tyagi Ramakrishnan

USF Tampa Graduate Theses and Dissertations

Human gait is a complex process that involves the coordination of the central nervous and muscular systems. A disruption to the either system results in the impairment of a person’s ability to walk. Impairments can be caused by neurological disorders such as stroke and physical conditions like amputation. There is not a standardized method to quantitatively assess the gait asymmetry of affected subjects. The purpose of this research is to understand the fundamental aspects of asymmetrical effects on the human body and improve rehabilitation techniques and devices. This research takes an interdisciplinary approach to address the limitations with current rehabilitation …


The Ecology Of Antibiotic Resistance: Sources And Persistence Of Vancomycin-Resistant Enterococci And Antibiotic Resistant Genes In Aquatic Environments, Suzanne M. Young Nov 2017

The Ecology Of Antibiotic Resistance: Sources And Persistence Of Vancomycin-Resistant Enterococci And Antibiotic Resistant Genes In Aquatic Environments, Suzanne M. Young

USF Tampa Graduate Theses and Dissertations

The growing crisis of antibiotic resistance is a major threat to ecosystems and human health. Infections caused by known and emerging antibiotic resistant pathogens are on the rise globally, with approximately 700,000 deaths per year caused by antibiotic resistant bacteria (1). In the United States, infections from antibiotic resistant bacteria cause more than 2 million illnesses and 23,000 deaths (2). Antibiotic resistant bacteria and antibiotic resistance genes are released into aquatic ecosystems through hospital waste, residential sewer lines and animal agricultural waste streams. Animal agriculture accounts for approximately 70% of antibiotic use in the United States (3). In agricultural ecosystems, …


Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati Nov 2017

Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati

USF Tampa Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) do not form stable tertiary structures like their ordered partners. They exist as heterogeneous ensembles that fluctuate over a time scale. Intrinsically disordered regions and proteins are found across different phyla and exert crucial biological functions. They exhibit transient secondary structures in their free state and become folded upon binding to their protein partners via a mechanism called coupled folding and binding. Some IDPs form alpha helices when bound to their protein partners. We observed a set of cancer associated IDPs where the helical binding segments of IDPs are flanked by prolines on both the sides. …


Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton Nov 2017

Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton

USF Tampa Graduate Theses and Dissertations

The emergence and proliferation of Gram-negative bacteria expressing β-lactamases is a significant threat to human health. β-Lactamases are enzymes that degrade the β-lactam antibiotics (e.g., penicillins, cephalosporins, monobactams, and carbapenems) that we use to treat a diverse range of bacterial infections. Specifically, β-lactamases catalyze a hydrolysis reaction where the β-lactam ring common to all β-lactam antibiotics and responsible for their antibacterial activity, is opened, leaving an inactive drug. There are two groups of β-lactamases: serine enzymes that use an active site serine residue for β-lactam hydrolysis and metalloenzymes that use either one or two zinc ions for catalysis. Serine enzymes …


Bioleaching Potential Of Filamentous Fungi To Mobilize Lithium And Cobalt From Spent Rechargeable Li-Ion Batteries, Aldo Lobos Nov 2017

Bioleaching Potential Of Filamentous Fungi To Mobilize Lithium And Cobalt From Spent Rechargeable Li-Ion Batteries, Aldo Lobos

USF Tampa Graduate Theses and Dissertations

Demand for lithium (Li) and cobalt (Co) is on the rise, due in part to their increased use in rechargeable Li-ion batteries (RLIB). Current recycling processes that utilize chemical leaching efficiently recover in Li and Co from the cathode material in spent batteries; however, these processes are costly and emit hazardous waste into the environment. Therefore, a more sustainable process for recycling Li and Co is needed, and bioleaching may provide a solution. Fungal bioleaching has been shown in previous studies to effectively mobilize metals (Pb, Al, Mn, Cu, and Zn) from mine tailings, electronic scrap, and spent batteries with …


Validation Of The Electronic Kids Dietary Index (E-Kindex) Screening Tool For Early Identification Of Risk For Overweight/Obesity (Ow/Ob) In A Pediatric Population: Associations With Quality Of Life Perceptions, Patricia A. Hall Nov 2017

Validation Of The Electronic Kids Dietary Index (E-Kindex) Screening Tool For Early Identification Of Risk For Overweight/Obesity (Ow/Ob) In A Pediatric Population: Associations With Quality Of Life Perceptions, Patricia A. Hall

USF Tampa Graduate Theses and Dissertations

Despite a worsening obesity epidemic and despite the American Medical Association (AMA) declaring Obesity a disease (2013), few assessment tools exist that assist practitioners who are charged with identifying risk for development of OW/OB in children. The Center for Health Statistics (2017) reported a 40% rate in obesity in the adult population and 18.5% in children in the U.S. Successful weight loss maintenance after 1 to 2 years of non-invasive treatment is less than 1%, indicating obesity is nearly incurable, making prevention imperative. Assessing risk for OW/OB in children has proven difficult given the lack of validated tools. The purposes …


Packaging Of Genetic Material By Gene Transfer Agents (Gtas) Produced By Marine Roseobacter Species And Their Effect On Stimulating Bacterial Growth, Shahd Bader Aljandal Nov 2017

Packaging Of Genetic Material By Gene Transfer Agents (Gtas) Produced By Marine Roseobacter Species And Their Effect On Stimulating Bacterial Growth, Shahd Bader Aljandal

USF Tampa Graduate Theses and Dissertations

Horizontal gene transfer is one of the most important mechanisms for prokaryotic genome innovation and evolution. Gene Transfer Agents (GTAs) are phage-like particles that package small fragments of the genome of a GTA-producing bacterial cell. GTA chromosomal gene clusters usually contain 15-conserved open reading frames (ORFs) and are present in most of the sequenced marine alpha-proteobacteria genomes. Some marine strains have been shown to produce GTA particles that were biologically active in marine environment.

GTA particles range in size, morphology and the amount of host DNA they package. To date, the characteristics of GTAs are largely based on observations of …


Reef Fish Biodiversity In The Florida Keys National Marine Sanctuary, Megan E. Hepner Nov 2017

Reef Fish Biodiversity In The Florida Keys National Marine Sanctuary, Megan E. Hepner

USF Tampa Graduate Theses and Dissertations

The biological diversity of reef-fish in the Florida Keys National Marine Sanctuary (FKNMS) from 1999 – 2016 was evaluated in terms of abundance, biomass, species richness, evenness, Shannon diversity, Simpson diversity, and functional diversity, using observations collected by multiple agencies and institutions under the Reef Visual Census (RVC) program. To compare the different diversity indices species richness, Shannon diversity, Simpson diversity, and functional diversity were converted into effective number of species. I examined the seven indices by no-take marine zones, in seven benthic habitat strata, and across the three-distinct geographic subregions in the Florida Keys domain (Upper, Middle, and Lower …


Perceptions Affecting Tree Valuation: An Analysis Of Recently Sold And Leased Properties In Tampa, Florida, Cody R. Winter Nov 2017

Perceptions Affecting Tree Valuation: An Analysis Of Recently Sold And Leased Properties In Tampa, Florida, Cody R. Winter

USF Tampa Graduate Theses and Dissertations

The urban forest is a structure that is fluid in both species composition and how it is integrated in our cities and suburban areas. Much like the fluidity in its structure, the urban forest provides ecosystem services and disservices in many forms. These services and disservices can often come in the form of temperature regulation, lower crime rates, and even higher property values. The latter, which is associated with the economic value of trees, is a part of the hedonic pricing literature which suggests that there is a disparity in the value associated with trees to house prices. With the …


Thermodynamic And Kinetic Aspects Of Hen Egg White Lysozyme Amyloid Assembly, Tatiana Miti Nov 2017

Thermodynamic And Kinetic Aspects Of Hen Egg White Lysozyme Amyloid Assembly, Tatiana Miti

USF Tampa Graduate Theses and Dissertations

Deposition of protein fibers with a characteristic cross-β sheet structure is the molecular marker associated with human disorders ranging from Alzheimer's disease to type II diabetes and spongiform encephalopathy. Given the large number of non-disease related proteins and peptides that have been shown to form amyloid fibrils in vitro, it has been suggested that amyloid fibril formation represents a generic protein phase transition. In the last two decades it has become clear that the same protein/peptide can assemble into distinct morphologically and structurally amyloid aggregates depending on the solution conditions. Moreover, recent studies have shown that the early stage, oligomeric …


Response To Nitrogen And Salinity Conditions In Rhizophora Mangle Seedlings Varies By Site Of Origin, Kristen L. Langanke Oct 2017

Response To Nitrogen And Salinity Conditions In Rhizophora Mangle Seedlings Varies By Site Of Origin, Kristen L. Langanke

USF Tampa Graduate Theses and Dissertations

Many coastal plant species thrive across a range of environmental conditions, often displaying dramatic phenotypic variation in response to environmental variation. We characterized the response of the critical foundation species Rhizophora mangle L. to full factorial combinations of salt and nitrogen (N). We used seedlings collected from five populations and measured traits related to salt tolerance and N amendment. The response to increasing salt included significant plasticity in succulence, leaf mass area (LMA), and root to shoot ratio (R:S). Seedlings also showed overall reduced maximum photosynthetic rate in response to N amendment, but this response depended on the level of …


Identifying New Treatment Options And Risk Factors For Type 2 Diabetes: The Potential Role Of Thymoquinone And Persistent Organic Pollutants, Shpetim Karandrea Oct 2017

Identifying New Treatment Options And Risk Factors For Type 2 Diabetes: The Potential Role Of Thymoquinone And Persistent Organic Pollutants, Shpetim Karandrea

USF Tampa Graduate Theses and Dissertations

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, which develops as a consequence of peripheral insulin resistance and defective insulin secretion from pancreatic β-cells. A high calorie diet coupled with physical inactivity are known risk factors for the development of T2DM; however, these alone fail to account for the rapid rise of the disease. Recent attention has turned to the role of environmental pollutants in the development of metabolic diseases. PBDEs (polybrominated diphenyl ethers) are environmental pollutants that have been linked to the development of type 2 diabetes (T2D), however, the precise mechanisms are not …


Cell Division Regulation In Staphylococcus Aureus, Catherine M. Spanoudis Oct 2017

Cell Division Regulation In Staphylococcus Aureus, Catherine M. Spanoudis

USF Tampa Graduate Theses and Dissertations

Cell division is a fundamental biological process that occurs in all kingdoms of life. Our understanding of cell division in bacteria stems from studies in the rod-shaped model organisms: Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. The molecular underpinnings of cell division regulation in non-rod-shaped bacteria remain to be studied in detail. Rod-shaped bacteria possess many positive and negative regulatory proteins that are essential to the proper placement of the division septa and ultimately the production of two identical daughter cells, many of which are absent in cocci. Given that essential cell division proteins are attractive antibacterial drug targets, it …


Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen Oct 2017

Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …


Microfluidic Biopsy Trapping Device For The Real-Time Monitoring Of The Tumor Microenvironment, Angela Holton Oct 2017

Microfluidic Biopsy Trapping Device For The Real-Time Monitoring Of The Tumor Microenvironment, Angela Holton

USF Tampa Graduate Theses and Dissertations

The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent …


Role Of Viruses Within Metaorganisms: Ciona Intestinalis As A Model System, Brittany A. Leigh Sep 2017

Role Of Viruses Within Metaorganisms: Ciona Intestinalis As A Model System, Brittany A. Leigh

USF Tampa Graduate Theses and Dissertations

Marine animals live and thrive in a literal sea of microorganisms, yet are often able to maintain specific associations that are largely dictated by the environment, host immunity and microbial interactions. Animal-associated microbiomes include bacteria and viruses that vastly outnumber host cells, especially in the gut environment, and are considered to be integral parts of healthy, functioning animals that act as a metaorganism. However, the processes underlying the initial establishment of these microbial communities are not very well understood. This dissertation focuses on the establishment of a well-known developmental animal model, Ciona intestinalis (sea squirt), to study the establishment and …


Freshwater Wetland Creation In A Changing Urban Environment: Designing For Long-Term Viability, Aaron Thomas Ryan Brown Jul 2017

Freshwater Wetland Creation In A Changing Urban Environment: Designing For Long-Term Viability, Aaron Thomas Ryan Brown

USF Tampa Graduate Theses and Dissertations

Urbanization and wetland mitigation are increasingly common in coastal watersheds with expanding populations. These mitigation wetlands are intended to offset the functional and structural losses experienced when natural systems are degraded or destroyed. In the Tampa Bay watershed, urbanization is both expanding into the upper reaches of the watershed and intensifying in previously-developed areas, resulting in the creations of hundreds of freshwater mitigation wetlands. This dissertation utilized an existing database of mitigation wetlands, publicly available data, and field surveys to investigate the relationship between constructed wetlands and their surroundings and also determine how design affects wetland condition over time. The …


Subtropical Benthos Vary With Reef Type, Depth, And Grazing Intensity, Kara R. Wall Jul 2017

Subtropical Benthos Vary With Reef Type, Depth, And Grazing Intensity, Kara R. Wall

USF Tampa Graduate Theses and Dissertations

Marine epibenthic communities are influenced by both pre- and post-recruitment processes. For instance, the larval supply and cues that influence settlement (pre-recruitment), as well as the growth and mortality of individuals (post-recruitment), may differ across reef type and depth. Determining the relative influence of these processes is important to understanding how epibenthic communities can develop in a region. Using both a recruitment experiment that controlled grazing by urchins and in situ photographic surveys of epibenthic communities, this study examined the recruitment and composition of epibenthos on natural limestone and artificial reefs in the eastern Gulf of Mexico (eGOM). In the …


Modeling Of Dynamic Allostery In Proteins Enabled By Machine Learning, Mohsen Botlani-Esfahani Jul 2017

Modeling Of Dynamic Allostery In Proteins Enabled By Machine Learning, Mohsen Botlani-Esfahani

USF Tampa Graduate Theses and Dissertations

Regulation of protein activity is essential for normal cell functionality. Many proteins are regulated allosterically, that is, with spatial gaps between stimulation and active sites. Biological stimuli that regulate proteins allosterically include, for example, ions and small molecules, post-translational modifications, and intensive state-variables like temperature and pH. These effectors can not only switch activities on-and-off, but also fine-tune activities. Understanding the underpinnings of allostery, that is, how signals are propagated between distant sites, and how transmitted signals manifest themselves into regulation of protein activity, has been one of the central foci of biology for over 50 years. Today, the importance …


Regulation Of Extracellular Signal-Regulated Kinase By Histone Deacetylase 6, Jheng-Yu Wu Jul 2017

Regulation Of Extracellular Signal-Regulated Kinase By Histone Deacetylase 6, Jheng-Yu Wu

USF Tampa Graduate Theses and Dissertations

Extracellular signal-regulated kinases 1/2 (ERK1/2) are important kinases regulating cell proliferation and cell migration, and have been established as therapeutic targets for cancer treatment. Previously, we found that ERK1 phosphorylates histone deacetylase 6 (HDAC6) to regulate its enzymatic activity. However, whether HDAC6 reciprocally modulates ERK1 activity is unknown. Here, we have discovered that ERK1/2 are acetylated proteins and shown that HDAC6 manipulates ERK1’s kinase activity via deacetylation. We demonstrated that both ERK1 and ERK2 interact with HDAC6 physically. We showed that the acetylation level of GST-ERK1/2 increased in a dose- and time-dependent manner upon treatment with a pan-HDAC inhibitor, Trichostatin …