Life Sciences Commons^™

Inhibition Of Rad18 By Arsenic, Lindsay B. Volk

Biomedical Sciences ETDs

Arsenite exposure leads to the retention of UV-induced DNA damage, thus burdening translesion synthesis (TLS). Rad18 is an essential factor in initiating TLS through PCNA monoubiquitination and is implicated in homologous recombination. It contains two functionally and structurally distinct zinc fingers that are potential targets for arsenite binding. Results from this study reveal arsenite binding to both zinc fingers of Rad18 and a corresponding loss of domain function. Importantly, arsenite inhibited Rad18 RING-dependent PCNA monoubiquitination and polymerase eta recruitment to DNA damage. Further analysis demonstrated multiple effects of arsenite, including the reduction in the nuclear localization and UV-induced chromatin recruitment …

Hepatocyte-Hepatic Stellate Cell Axis In Potentiation Of Alcohol And Hiv-Induced Liver Injury, Moses O. New-Aaron

Theses & Dissertations

Human Immunodeficiency Virus (HIV) remains a global threat, with approximately 38.4 million active infections and 33 million HIV-related deaths since the first case. While many may be tempted to think of HIV as a relic of the past, emerging data suggests otherwise. By the end of 2021, approximately 1.5 million HIV incidences and 650 000 mortalities were reported globally. The etiologies of HIV-related mortality are numerous. Liver disease is one of the leading etiologies of HIV-related mortality, especially in recent times of antiretroviral therapy (ART)-induced longevity among people living with HIV (PLWH). While co-infections with hepatotropic viruses notoriously contribute to …

Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder

Honors College Theses

Photodynamic therapy (PDT) is considered to be a potential replacement for traditional methods of chemotherapy. It includes the administration of photosensitizing agents (PS), which generate reactive oxygen species (ROS) upon excitation at a specific wavelength. With new outlooks and techniques, cancer research is advancing each day. It has allowed the progress of several theranostic drug delivery systems (DDS) exploring the area of nanomedicine.2 In the present work, a Rhodamine derivative, Rhodamine 6G (R6G) was used as the PS. In general, rhodamine compounds undergo cytotoxic reactions on photoexcitation by electron transfer reactions with folic acid within cells, making them a favorable …

Effects Of Microcystin-Lr On Channel Catfish (Ictalurus Punctatus) Susceptibility To Microbial Pathogens (Aeromonas Hydrophila And Edwardsiella Piscicida), Alison Marchant

Theses and Dissertations

Microcystin-LR is a hepatotoxin produced by cyanobacteria. Aeromonas hydrophila and Edwardsiella piscicida infections are leading causes of losses in market-sized channel catfish (Ictalurus punctatus). These older fish should have natural immunity in place and a predisposing factor is likely a prerequisite for these disease outbreaks. While microcystin-LR rarely causes mortality in warm-water aquaculture, we believe it may be a predisposing factor that leads to bacterial disease outbreaks during the summer months due to its ability to damage the liver. Our study investigated microcystin-LR’s effects on channel catfish susceptibility to these pathogens. We found that a sublethal dose of microcystin-LR induced …

Quantifying The Toxicological Effects Of The Organic Uv Filters Avobenzone And Homosalate On Acropora Cervicornis, Samantha F. Buckley

All HCAS Student Capstones, Theses, and Dissertations

Reports of the environmental effects of organic UV filters such as oxybenzone have led to the marketing of “reef-safe” sunscreen ingredients, including avobenzone and homosalate. Avobenzone provides broad-spectrum UV protection which blocks higher wavelength UV rays, the leading cause of aging and skin cancer. However, as polycyclic aromatic hydrocarbons (PAHs), organic UV filters have similar structures to crude oil and estrogens, some of which have been labeled endocrine disrupters. Common in personal care products, UV filters enter marine ecosystems via wastewater effluent and swimmers. Significant stress and mortality have been observed in juvenile and some adult scleractinian corals after exposure …

Morphine-Induced Tolerance Is Reduced By The Consumption Of A Ketogenic Diet, But Not A High Fat/High Carbohydrate Diet, Nina Beltran

Open Access Theses & Dissertations

Opioid drugs like morphine are used medicinally for pain relief, but also have abuse liability that can lead to opioid use disorder (OUD), which contributes to nearly 70% of drug overdose deaths in the United States. Another rising health concern is the global obesity epidemic, and new evidence suggests that obesity and OUD might converge to impact individuals. For example, high body mass index (BMI) is associated with greater reports of pain among women. Further, opioid overdose risk is increased among individuals diagnosed with obesity, suggesting a potential relationship that might convey enhanced vulnerability among some populations. Given the high …

The Evergreen Challenges Of Healing: An Evaluation Of Urban Green Space In Harambee, Kacee Ochalek

Theses and Dissertations

Urban green space initiatives have emerged in low- and middle-income cities as a solution to disinvestment, the production of more positive public health metrics, and a tool of community engagement. While the production of urban greening provides ample room for applause, The City of Milwaukee’s Healing Spaces Initiative model regarding the ongoing construction of green space and the implementation of maintenance creates challenges that perpetuate racist capitalistic notions of the neoliberal project. This paper presents reports from participant observation, document analysis, and 17 qualitative interviews with representatives of the City of Milwaukee, community partners, garden leaders, and residents. The data …

Insights On The Behavior Of Nano-Copper In The Agroecosystem: Mycorrhizal Associations With Spearmint (Mentha Spicata), Suzanne Annette Apodaca

Open Access Theses & Dissertations

Nanotechnology offers significant potential benefits to our society, including the agriculture sector. With the advancement of nano-enabled agrochemicals towards sustainable and efficient agricultural practices, it is essential to address environmental issues associated with the use of nanoscale materials. The same properties that give promise to applications of nanotechnology in modern agriculture could have unintended consequences on ecosystem dynamics. A point of concern for risk management is the impact of engineered nanomaterials (ENMs) to beneficial microbial communities, which support a variety of ecosystem services.

Use of copper (Cu) products in agriculture are based on their abundance, role as a micronutrient, and …

Health Effects Of Neonicotinoids On An Agricultural Community, Jocelyn Rodriguez-Paar

Capstone Experience

Mead, Nebraska, a small United States agricultural community consisting of approximately 600 people, was accidentally exposed to high amounts of neonicotinoids when AltEn, an ethanol plant that used neonicotinoid coated corn and soybean seeds for biofuel, was discovered not disposing of the toxic byproduct safely. Coincidentally, there was also a leak in their wastewater system that also contaminated the nearby areas. Although neonicotinoids are not considered highly dangerous with low dose exposures, large dose exposures can cause symptoms similarly to nicotine poisonings, such as difficulty breathing, vomiting, nausea, hypertension, tachycardia, and lethargy (Imamura, T. et al., 2010). Neonicotinoid poisoning can …

Effects Of Titanium Dioxide Nanoparticle Injections On Tissue Function And Morphology In Goldfish (Carassius Auratus), Bryan Joel Patterson

Graduate Theses

Fish gills are sensitive to a variety of environmental factors because they regulate the exchange of oxygen and ions between the fish and the external environment. This study examined the effects of polyacrylic acid (PAA) coated titanium dioxide nanoparticle injections (TiO₂ NPs) on goldfish (Carassius auratus) over 14 days. Following the experimental period, we examined gill histological samples and looked for signs of an inflammatory response through blood glucose levels and relevant gene expression. TiO₂ injected fish developed a more robust ILCM (interlamellar cell mass) compared to the non-injected controls, which remained elevated over 14 days post injection. …

Developmental Effects Of Chronic Low-Level Arsenic Exposure In Mouse Embryonic Stem Cells And In Human Induced Pluripotent Stem Cells, M. Chiara Perego

All Dissertations

Arsenic is an environmental contaminant commonly found in food and drinking water. Exposure to arsenic during embryonic development has been linked to reduced muscle growth, disrupted muscle development and locomotor activity, impaired neurodevelopment, reduced IQ, impaired memory and learning deficits. While the mechanisms responsible for developmental changes following in utero exposure to arsenic are not well known, one possibility is that arsenic might disrupt proper cellular differentiation. Therefore, we aimed to investigate the mechanisms by which arsenic exposure could alter stem cell differentiation into neurons.

First, we continuously exposed P19 mouse embryonic stem (ES) cells to 0.1 μM (7.5 ppb) …

Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …

The Impact Of Pharmacogenetics On Oral Fluid Steady State Drug Testing Results, Aliya D. Lewis

Student Theses

Pharmacogenetics refers to the relationship between phenotypic variation in metabolism and response to certain drugs. The interface of pharmacogenetics and forensic toxicology is not well explored. A major component of the opioid metabolic pathway has to do with a family of cytochromes called cytochrome P450 (CYP450). CYP450 refers to a general family of enzymes capable of catalyzing the oxidative biotransformation of lipophilic substances, CYPs are further categorized into families and sub-families (Roller, 2015; Zanger & Schwab, 2013). The gene CYP2D6 belongs to the CYP2 family which is responsible for the biotransformation of xenobiotics. This study looked at the effect of …

The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall

Electronic Theses and Dissertations

Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …

Understanding Effect Of Ionic Liquid On Metalloproteins: Laccase And Azurin, Aashka Y. Patel

Theses and Dissertations

Interactions between ionic liquids and biomolecules have been of great interest due to the intrinsic properties of ionic liquids and the flexibility to mix and match cations and anions to create unique ionic liquids. A number of ionic liquid-biomolecule studies have focused on the interactions with proteins, including industrially relevant enzymes. One of these, laccase from Trametes versicolor, is a naturally derived enzyme used in the breakdown of phenolic compounds in a wide variety of industries, especially useful in breakdown of lignocellulosic materials. Here, a combination of experiments and molecular dynamics (MD) simulations were used to investigate the interactions …

An In Silico Study Of The Delta Opioid Receptor Using Small Molecules, Emily Dean

Theses and Dissertations

The DOR is the least studied out of the three opioid receptors (Mu, Kappa, and Delta). The most is known of the Mu Opioid receptor (MOR) and the drugs that target it have led to the global opioid epidemic due to their adverse effects of tolerance and addiction. The DOR is not known for the same adverse effects and therefore, is a promising pharmacological target for the development of new opioid ligands. In this thesis, molecular modeling, simulations and other computational methods are introduced in Chapter 1 where these methods are used to study the activation mechanism of DOR (Chapter …

Esterase Mediated Insecticide Resistance In The Southern House Mosquito, Culex Quinquefasciatus, Vivek Pokhrel

LSU Doctoral Dissertations

Much is known about the development of insecticide resistance associated with targeted application against insect populations. However, off-target selection by applications of insecticides in agricultural and residential sites also impacts development of insecticide resistance and is understudied. Similarly, the impact of selecting one life stage of mosquitoes on the insecticide susceptibility of different life stages is largely unknown. The first part of this study shows that susceptibility to chlorantraniliprole, which is applied in rice and sugarcane fields in LA, decreased (5.7 to12-fold) in populations of Culex quinquefasciatus collected from near these fields compared to a reference field strain. In addition, …

Comparison Of The Humoral Immune Response Following Both Bacterial Challenge And Rnai Of Major Factors On Proliferation Of Bartonella Quintana In The Human Louse, Jake Zina

Masters Theses

Human body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, have been hematophagous ectoparasites of humans for thousands of years. Despite being ecotypes, only body lice are known to transmit bacterial diseases to humans, and it appears that lower humoral and cellular immune responses allow body lice to possess a higher vector competence. We previously observed that the transcription level of the defensin 1 gene was up-regulated only in head lice following oral challenge of Bartonella quintana, a causative agent of trench fever, and also that body lice excreted more viable B. quintana in their …

The Mouse Mammary Gland: A Tool To Evaluate The Environmental Chemical Butyl Benzyl Phthalate, And Approaches To Improve Regulatory Testing, Jessica Daum

Masters Theses

In the first part of this thesis, we utilize the mouse model to evaluate the environmental chemical Butyl Benzyl Phthalate. Due to lack of research on female exposure to BBP, this thesis focuses on quantifying the effects of gestational exposure on the female mammary gland Here male and female parental mice were exposed before mating and through pregnancy and lactation to one of three doses of BBP or the control via oral ingestion. After weaning, offspring were sacrificed at puberty or early adulthood and evaluated for altered mammary gland morphology or hormonal receptor expression. Results indicate a persistent statistically significant …

Effect Of Hyperoxia On Cardiac Pathophysiology In Female Guinea Pig Hearts, Chayapatou Chayawatto

USF Tampa Graduate Theses and Dissertations

Hyperoxia is widely implemented in critical care and ICU patients. The administration of a high concentration of inspired oxygen to the lung can unknowingly cause hyperoxia and thereby damaging the lungs and heart due to oxidative stress. Technically, hyperoxia occurs when the patient receives PaO2 > 200 mmHg. Major research focused on hyperoxia-induced lung injury, but nothing is known on its effect on heart. Our lab is the pioneer in understanding the effect of hyperoxia on cardiovascular remodeling using mice model. Previous results show that mice under 72 hours of hyperoxia present severe cardiac pathophysiology. This research uses Guinea pigs, which …

Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin

Doctoral Dissertations

The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …

Association Between Use Of Remdesivir And Bradycardia, Gibret Umeukeje

USF Tampa Graduate Theses and Dissertations

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see …

Screening Pathological Protein Specific Antibodies As Biomarker Discovery Tools For Neurodegenerative Disease, Yitong Li

USF Tampa Graduate Theses and Dissertations

With the increase in the average life span, the incidence of neurodegenerative diseases also increases, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common types of neurological disorders. AD and PD share the same pathogenic mechanism that involves a class of proteins called beta-amyloid (Aβ), which, under the induction of some factors, changes from its natural monomeric state to the oligomers containing β-sheet, which is neurotoxic and thus leads to cell damage or apoptosis. This study focused on the selection of antibodies used as biomarkers for AD and PD. The selection of antibodies was based …

The Effect Of Oatp2b1-Mediated Statin Transport On Beta Cell Dysfunction, Jihoon Kwon

Electronic Thesis and Dissertation Repository

Statins are a class of cholesterol-lowering drugs which work by inhibiting the mevalonate pathway. Statin treatment has been linked to an increase in the risk of new-onset diabetes mellitus, and previous studies have suggested impairment in insulin secretion following statin treatment. Recent work from our laboratory confirmed the expression of organic anion transporting polypeptide 2B1 (OATP2B1), an important statin uptake transporter, in human pancreatic beta cells. Our study examined the role of OATP2B1 in statin-associated beta cell toxicity using INS-1 cells as a beta cell model. We showed that OATP2B1 augments cellular accumulation of rosuvastatin and atorvastatin, but not pravastatin. …

Coastal Stormwater Pond Pollutants And The Potential For Development Of Antimicrobial Resistance In Vibrio And Enterococcus Bacteria, Cassandra L. Horton

Theses and Dissertations

The Southeastern coastal plain is the most rapidly urbanizing region in the United States. Associated landscape changes which increase imperviousness lead to hydrological cycle alterations, increasing runoff of nonpoint source (NPS) pollution. Urban and agricultural NPS runoff is generally discharged into stormwater ponds, which sequester chemical contaminants, nutrients, and microbes to reduce loading into coastal ecosystems. Studies of these ponds have indicated elevated levels of trace metals, antimicrobial compounds, and bacterial contamination (SCSGC 2018).

Interactions of aquatic pathogens Vibrio vulnificus and Enterococcus faecium with trace metals (arsenic, copper, zinc) and clinically relevant antimicrobials (triclosan, ciprofloxacin, oxytetracycline) commonly found in coastal …

Xenobiotic Exposures On Women’S Reproductive Health, Maria Zubizarreta Mcclam

Theses and Dissertations

Environmental and chemical exposures are continually introduced into our bodies. The female reproductive cycle is complex and particularly sensitive to toxic substances. A recent rise in infertility and reproductive diseases and cancers make reproductive toxicity a public health concern. The overall purpose of this dissertation is to explore how environmental and chemical exposures impact women’s reproductive health and overall wellbeing. To do this, a variety of topics related to women’s reproductive health are explored, including how environmental exposures can impact reproduction, methods for studying reproductive dysfunctions, fertility preservation among cancer patients, and the overall wellbeing of female cancer patients.

The …

Monitoring Titanium Dioxide Engineered Particles In Rural And Urban Surface Waters, Md Mahmudun Nabi

Theses and Dissertations

Quantifying and characterizing engineered particles in environmental systems is key for assessing their risk but remains challenging and requires the distinction between natural and engineered particles. The Ph.D. dissertation research described in this thesis contributes to the current attempts to improve environmental nanoparticle analysis and better understand nanoparticle behavior in natural systems, with the focus being on natural streams, and the application of single particle inductively coupled plasma-time of flight-mass spectrometry (SP-ICP-TOF-MS) for distinguishing and tracing the origins of environmental nanoparticles. The objective of this dissertation is to characterize and quantify the concentrations of titanium dioxide engineered particles in urban …

Absence Of Enhancer Of Zeste Homolog 2 Promotes The Progression Of Kras-Driven Pancreatic Ductal Adenocarcinoma, Xiaoyi Wang

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRAS^G12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRAS^G12D-driven PDAC. I hypothesized that EZH2 restricts KRAS^G12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRAS …

Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato

Masters Theses

Poly- and perfluoroalkyl substances (PFAS) are a class of bioaccumulative toxicants used in numerous industrial and commercial products. Perfluorooctanesulfonic acid (PFOS) alters pancreatic organogenesis during development, and perfluorohexanesulfonic acid (PFHxS) has been suggested as a replacement for PFOS due to its shorter carbon chain, but they are often found together in surfactants, such as legacy aqueous film-forming foam. This study investigates how developmental exposures to a PFAS mixture (PFHxS + PFOS) impact the developing exocrine pancreas. Zebrafish embryos (Tg(ptf1a:GFP)) were exposed to 0.01% DMSO, or 8, 16, 32 μM PFHxS alone, 16 μM PFOS alone, and 8, 16, and 32 …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …