Biochemistry, Biophysics, and Structural Biology Commons^™

Wdr5 Network Analysis Using Ensemble Approaches, Ali Imran

Dissertations - ALL

Understanding the properties of protein-protein interactions (PPIs) is necessary to deconvolute the processes inside living organisms. As such, research in this regard has significant implications for gaining insight into cancers and other diseases. Once understood, drugs can be designed to target these diseases. In these chapters we focus on the network of interactions of WD40 repeat protein 5 (WDR5), a known hub protein. Several of its interactions are significant for regulation of histone methylation and consequently epigenetic regulation. These interacting partners include the SET1 family of proteins and retinoblastoma binding protein-5 (RbBP5). In this work we used multiple ensemble measurement …

The Apoe Ε4 Allele Association With Cholesterol Related Phenotypes In The Mexican American Population, Stephanie Lozano

Theses and Dissertations

Diseases linked to high cholesterol have been well studied and several diseases-associated candidate genes have been suggested. Among these, the apolipoprotein E gene (APOE) gene associated with lipid metabolism and lipid-related traits was reported in the non-Hispanic population. There are three types of alleles APOE ε2, ε3, and ε4. The APOE ε4 allele has been identified as a biomarker for Alzheimer’s disease (AD) and cardiovascular disease (CVD). In recent years, there have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Mexican American population. Therefore, the aim of this study is to investigate …

Characterization Of The Responses To Chronic Stress In Caenorhabditis Elegans, Amy Laura Knight

Theses and Dissertations

Exposure to chronic temperature stress influences organismal phenotypes that are important for human health, agriculture, and ecology. In this thesis, the model organism Caenorhabditis elegans was used to study the effects of temperature stress on reproduction and lifespan. It was found that worms demonstrated a rapid shut down in egg-laying between 18-24 hours of exposure to 28°C. Despite this reproductive defect, the overall lifespan of worms was unaffected. At the molecular level, heat shock factor 1 (HSF-1), a regulator of the protective molecular pathway known as the heat shock response (HSR), was identified as important for progeny production during heat …

Cucurbitacin B: A Potential Natural Agent For Targeting Tumor Immune Cell Population, Emmanuel Anning

Theses and Dissertations

Immune checkpoint blockade (PD1, PDL-1 and CTLA-4) immunotherapies have emerged as the breakthrough in cancer treatment. However, some malignancies show marginal response. One factor that influences the efficacy of immunotherapy is the development of immunosuppressive tumor microenvironment (TME), caused by infiltration of myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAM) into the tumor, facilitating metastatic tumor growth and immunotherapy resistance. We have identified Cucurbitacin B (Cuc. B), a potent small molecule that targets TAM and MDSCs and inhibits Stat3, CSF-1R, and PI3Kγ signaling axis at lower doses compared to the pharmacological inhibitor of PI3Kγ (IPI-549). IL-4 polarization of …

Targeting Mutated Kras And Galectin-1 In Pancreatic Cancer, Ana Izavelle Martinez Bulnes

Theses and Dissertations

The poor patient survival rate in pancreatic ductal adenocarcinoma (PDAC) remains a challenge. KRAS activating point mutation on codon-12 is found in 70–95 percent of PDAC patients, and no progress in inhibiting KRAS has been obtained thus far. KRASG12D is a transcription factor that controls cell proliferation, differentiation, and apoptosis. Recent preliminary and published research indicates that Galectin-1 (Gal-1) levels are high in both PDAC and stromal cells, which modulates tumor microenvironment and metastasis. As a result, we created a new combination treatment for PDAC that targets both proliferation and metastasis in PDAC by targeting mutant KRASG12D and Gal-1. This …

Screening For Potential Therapeutic Targets Of Yb-1 Protein Using A Bioinformatics Approach, Omar Muneer Karkoutly

Theses and Dissertations

Treatment options for cancer are becoming much more limited due to the robust characteristics of cancer that allows them to rapidly develop drug resistance. This may be a result of cancer cells’ ability to switch between differentiated and undifferentiated states (plasticity). Diagnostic measurement and detection of cancer and its progression is essential for developing successful treatments. Specific cancer targets whose expressions are highly associated with increased incidence, risk, and spread of cancer therefore become perfect targets for therapeutic intervention. One such novel target that is still being studied is the Y-box binding protein 1 (YB-1), which …

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …

Water-Soluble Porphyrin Complexes For The Biological Inactivation Of Fentanyl, Anneli Nina

Theses and Dissertations

This work aimed to investigate the degradation of fentanyl in aqueous solutions using unsupported water-soluble cobalt(III) porphyrins (55 and 56), AuNP supported water-soluble cobalt(III) porphyrins (67 and 68), and liposome supported water-soluble cobalt(III) porphyrins (69 and 70). Complexes 55, 56, 68, and 69 have been shown to remove fentanyl from aqueous solutions at 37 ºC. The degradation of fentanyl, and the identification of breakdown products were analyzed with the use of time-of-flight mass spectrometry (TOFMS). Complex 55 has been shown to completely degrade fentanyl at 37 ºC in as little as two hours with a 400 mol% catalyst loading. Complex …

Monkeypox: A Contemporary Review For Healthcare Professionals, Boghuma K Titanji, Bryan Tegomoh, Saman Nematollahi, Michael Konomos, Prathit A Kulkarni

Faculty, Staff and Students Publications

The ongoing 2022 multicountry outbreak of monkeypox is the largest in history to occur outside of Africa. Monkeypox is an emerging zoonotic disease that for decades has been viewed as an infectious disease with significant epidemic potential because of the increasing occurrence of human outbreaks in recent years. As public health entities work to contain the current outbreak, healthcare professionals globally are aiming to become familiar with the various clinical presentations and management of this infection. We present in this review an updated overview of monkeypox for healthcare professionals in the context of the ongoing outbreaks around the world.

Chronic Lung Allograft Dysfunction, Anupam Kumar, Puneet Singh Garcha

Faculty, Staff and Students Publications

Lung transplantation remains the only cure for selected patients with advanced irreversible lung diseases. More than 4000 lung transplants are performed worldwide annually. In the last two decades, significant advances have been made in this arena, the most impactful being a modest but improved survival of the recipients. Unfortunately majority of recipients still succumb to chronic lung allograft dysfunction (CLAD), and it remains the most common cause of death after the first year of transplantation. Below is a concise review of the current definition of CLAD, including the various phenotypes, and a brief discussion of the tools available for its …

Methanogen Metabolic Flexibility, Sean R. Carr

School of Biological Sciences: Dissertations, Theses, and Student Research

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …

Targeting Ribosome Biogenesis For Pancreatic Cancer Treatment, Carlos Perez Iii

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related death in the United States. Currently, PanCa is one of the recalcitrant cancers that has very limited therapeutic options available for its treatment. The current standard care of PanCa is gemcitabine (GEM) alone or in combination with FOLFIRINOX, nab-paclitaxel, erlotinib, or 5-FU PanCa, which often show poor response. Therefore, new treatment strategies are required for the prevention and treatment of cancer. Ribosome biogenesis process is dysregulated in most of the cancer types of results in production of more ribosomes and synthesis of oncoproteins which lead to the induction, progression, …

Spatial Analysis Of Drug Absorption, Distribution, Metabolism, And Toxicology Using Mass Spectrometry Imaging, Michelle L Spruill, Mirjana Maletic-Savatic, Howard Martin, Feng Li, Xinli Liu

Faculty, Staff and Students Publications

Mass spectrometry imaging (MSI) is emerging as a powerful analytical tool for detection, quantification, and simultaneous spatial molecular imaging of endogenous and exogenous molecules via in situ mass spectrometry analysis of thin tissue sections without the requirement of chemical labeling. The MSI generates chemically specific and spatially resolved ion distribution information for administered drugs and metabolites, which allows numerous applications for studies involving various stages of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). MSI-based pharmacokinetic imaging analysis provides a histological context and cellular environment regarding dynamic drug distribution and metabolism processes, and facilitates the understanding of the spatial pharmacokinetics …

Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett

USF Tampa Graduate Theses and Dissertations

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene …

A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds, Graham L. Strauss

USF Tampa Graduate Theses and Dissertations

Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay …

Activating Connexin43 Gap Junctions Primes Adipose Tissue For Therapeutic Intervention, Yi Zhu, Na Li, Mingyang Huang, Xi Chen, Yu A An, Jianping Li, Shangang Zhao, Jan-Bernd Funcke, Jianhong Cao, Zhenyan He, Qingzhang Zhu, Zhuzhen Zhang, Zhao V Wang, Lin Xu, Kevin W Williams, Chien Li, Kevin Grove, Philipp E Scherer

Faculty, Staff and Students Publications

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic …

Effect Of A Commonly Used Veterinary Antibiotic On Oxidative Stress And Root Transporters Of Edible Legumes And Leafy Crops, Safaa Nassar, Jamilah Borjac

BAU Journal - Science and Technology

Antibiotic accumulation in soil and plants is a rising problem in agriculture creating a serious threat to living organisms in the environment, hence needing huge attention. To this end, glasshouse pot experiments were conducted to simulate contamination by veterinary antibiotic at 150 mg kg^-1 and 4800 mg kg^-1 in a virgin soil in which lentil (Lens culinaris Medik.), chickpea (Cicer arietinum L.), arugula (Eruca sativa Mill.) and cress (Lepidium sativum L.) were grown, aiming at evaluating the potential toxicity of antibiotic in plants roots during their growth period. Biomarkers of toxicity such as malondialdehyde and proline …

Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett

Dissertations

2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …

Dual-Mode Tumor Imaging Using Probes That Are Responsive To Hypoxia-Induced Pathological Conditions, S A Amali S Subasinghe, Robia G Pautler, Md Abul Hassan Samee, Jason T Yustein, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used …

New Simple And Robust Method For Determination Of Polarity Of Deep Eutectic Solvents (Dess) By Means Of Contact Angle Measurement, Łukasz Cichocki, Dorota Warmińska, Justyna Łuczak, Grzegorz Boczkaj, Andrzej Przyjazny

Natural Sciences Publications

The paper presents a new method for evaluating the polarity and hydrophobicity of deep eutectic solvents (DESs) based on the measurement of the DES contact angle on glass. DESs consisting of benzoic acid derivatives and quaternary ammonium chlorides–tetrabutylammonium chloride (TBAC) and benzyldimethylhexadecylammonium chloride (16-BAC)—in selected molar ratios were chosen for the study. To investigate the DESs polarity, an optical goniometer and an ET(30)" role="presentation" style="box-sizing: border-box; max-height: none; display: inline; line-height: normal; font-size: 13.2px; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(34, 34, 34); font-family: Arial, …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …

Nanophotonics And Nanomaterials For Microbial Inactivation, Sharad Ambardar

USF Tampa Graduate Theses and Dissertations

The study of light-matter interaction at nanoscale, also termed as nanophotonics, has gained vast attention due to its multidisciplinary application in the field of chemical engineering for the synthesis of nanomaterials, in the field of physics to study non-linear optical processes and optical phenomena in nanocavities and in the field of biology, biomedicine to study and develop novel optical nanoprobes for diagnostics, nanobiosensing and near-field imaging.

We studied UV-irradiation-based inactivation of SARS-CoV-2 and other respiratory viruses. In this work, we fabricated a device comprising a pulsed nanosecond 266 nm UV laser coupled to an integrating cavity (LIC), composed of a …

Deciphering Phosphoprotein Phosphatase Signaling Networks Using Proteomics Approaches, Brooke Brauer

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a highly regulated mechanism of cell signaling control and its deregulation is implicated in disease. The kinases that catalyze the addition of phosphate groups onto their substrate proteins have been well studied, their signaling pathways mapped, and their effects on cell and organismal health observed. Knowledge of the phosphatases that reverse the reaction only recently began to come into focus. Phosphoprotein phosphatases (PPPs), long thought to be housekeeping enzymes, are now known to be exquisitely specific towards their substrates, but the exact nature of phosphatase regulation—both upstream and downstream of the phosphatase—is unclear.

PPPs recognize substrates through …

Ten Steps To Organize A Virtual Scientific Symposium And Engage Your Global Audience, Jiye Son, Jasmine Sabio, Ankit Jain, Rein V. Ulijn

Publications and Research

The paper describes guidelines for the planning, organization, and successful execution of virtual, global scientific conferences for global audiences. The guidelines are based on experience and lessons learned during the organization of the 3-day 2020 Virtual Systems Chemistry Symposium hosted on Zoom webinar and Twitter, held on May 2020 with over 1000 registered participants from 46 different countries.

Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta

Department of Biochemistry: Faculty Publications

Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly …

Crispr/Cas13 Effectors Have Differing Extents Of Off-Target Effects That Limit Their Utility In Eukaryotic Cells, Yuxi Ai, Dongming Liang, Jeremy E Wilusz

Faculty, Staff and Students Publications

CRISPR/Cas13 effectors have garnered increasing attention as easily customizable tools for detecting and depleting RNAs of interest. Near perfect complementarity between a target RNA and the Cas13-associated guide RNA is required for activation of Cas13 ribonuclease activity. Nonetheless, the specificity of Cas13 effectors in eukaryotic cells has been debated as the Cas13 nuclease domains can be exposed on the enzyme surface, providing the potential for promiscuous cleavage of nearby RNAs (so-called collateral damage). Here, using co-transfection assays in Drosophila and human cells, we found that the off-target effects of RxCas13d, a commonly used Cas13 effector, can be as strong as …

Ceramide-1-Phosphate: A Novel Regulator Of Golgi Fragmentation, Golgi-Er Vesicle Trafficking, And Anaplasma Phagocytophilum Pathogenesis, Anika Nayar Ali

USF Tampa Graduate Theses and Dissertations

Anaplasma phagocytophilum, the etiologic agent of human granulocytic anaplasmosis (HGA), is a tick transmitted obligate intracellular bacterium that infects granulocytes, bone marrow progenitor cells and endothelial cells. HGA exhibits symptoms of febrile illness including fever, chills, headache, malaise, leukopenia and elevated liver enzymes which are treatable by antibiotics. However, elderly and immunocompromised patients are at a greater risk of developing fatal complications. Inside the host cell A.phagocytophilum resides in host cell derived vacuole called A.phagocytophilum occupied vacuole (ApV) where it undergoes its biphasic lifecycle. Being an intracellular pathogen, A.phagocytophilum relies heavily on nutrient acquisition from host cell and to obtain …

Exploring Melatonin As A Treatment For Oral Ulcers, William H. Sutherland

Undergraduate Honors Theses

The hormone melatonin is best known for its role in the sleep-wake cycle, but its anti-inflammatory and antioxidant effects have significant implications that have not been fully explored in oral health. Some studies use melatonin to treat gastrointestinal ulcers, including duodenal ulcers and oral mucositis, but we found no study reporting its effects on more common oral ulcers, like aphthous stomatitis. We hypothesize that the anti-inflammatory and antioxidant characteristics of melatonin could effectively prevent and heal oral ulcers. In this paper, we review the literature on melatonin to propose its use as a treatment for oral ulcers. We also include …

17Β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation Of Mesenteric Arteries In Ovariectomized Uc Davis Type 2 Diabetes Mellitus Rats In Prediabetic State, Md Rahatullah Razan, Farjana Akther, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted …