Pharmacology, Toxicology and Environmental Health Commons^™

Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu

Theses and Dissertations

Adeno-associated virus (AAV) is a widely used vector for gene therapy. However, few studies have focused on producing AAV-based virus-like particles (VLP) in E. coli. This project aimed to express VP3 of AAV2 or co-express VP3 of AAV2 with other proteins, such as E. coli chaperones and/or assembly-activating protein (AAP) in E. coli under different expression conditions and explore the potential to produce VP3-only VLP of AAV2 in situ in E. coli. The constructed plasmid pET15ΔHis-VP3 was used to express VP3 under different conditions. The results demonstrated that most expressed VP3 was in inclusion bodies in all tested conditions. Although …

Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos

Theses and Dissertations

The dendritic cells of the CNS, the microglia (MG), are an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia morphology drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there is much to be learned about MG metamorphosis from a baseline (M2) to an activated (M1) state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury. This isolates dendritic cellular responses and associated …

Mobocertinib Antagonizes Multidrug Resistance In Abcb1- And Abcg2-Overexpressing Cancer Cells, Xingduo Dong

Theses and Dissertations

The resistance of cancer cells to multiple drugs, known as multidrug resistance (MDR), remains a significant obstacle that leads to the ineffectiveness of cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, has been strongly correlated with MDR. There is an urgent need to explore and identify novel inhibitors targeting ABCB1 and ABCG2 to overcome the related MDR. Mobocertinib (TAK-788) is an orally administered, irreversible EGFR/HER2 inhibitor approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations. This study …

Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid

Theses and Dissertations

The herbicide glyphosate and the fungicide mancozeb are globally applied on a variety of agricultural crops. Residues of both pesticides are frequently detected in food and water. Combined exposure to both compounds is therefore possible. Glyphosate and mancozeb have been separately investigated in previous studies and were shown to induce neurotoxicity. The current study investigates the cytotoxicity of different glyphosate and mancozeb combinations including mixture of mancozeb + glyphosate, combination of mancozeb followed by glyphosate and combination of glyphosate followed by mancozeb and compares neurotoxicity seen with the combinations to that of glyphosate or mancozeb using mouse neuroblastoma Neuro-2a cells. …

Characterization Of The Hydroxyurea-Induced Cell Elongation Phenotype In Fission Yeast Ssb1-20 Mutant, Yeseswi Archana Guduri

Browse all Theses and Dissertations

Eukaryotic SSB, also known as replication protein A (RPA), is a single-stranded DNA binding protein that is highly conserved in eukaryotes. It is essential in multiple cellular functions such as DNA replication, repair, recombination, and cell cycle checkpoint signaling. Studying SSB’s or RPA’s checkpoint functions in cells is challenging due to its crucial role in cell survival. Exploring this possibility, we performed an extensive genetic screening of ssb1, which encodes the largest subunit of RPA, looking for nonlethal mutants that lack the checkpoint function. This screen has identified 25 primary mutants that are sensitive to genotoxins namely HU and MMS. …

The Impact Of Maternal Thyroid Dysfunction During Pregnancy On Fetal Development, Ariella Eisig

The Science Journal of the Lander College of Arts and Sciences

Thyroid dysfunction during pregnancy significantly impacts both maternal and fetal health, posing physical and neuropsychological development risks for the neonate. This paper reviews the mechanism of thyroid function, the etiology, screening for hypothyroidism and hyperthyroidism, and the effects on fetal development and pregnancy outcomes. Multiple studies have shown that maternal thyroid dysfunction can lead to various complications such as IUGR, preterm birth, neonatal Grave’s disease, and adverse neuropsychological outcomes in children. Proper screening, monitoring, and management of maternal thyroid function are essential to lessen these risks and ensure optimal fetal development. Further research is warranted to better understand the complex …

Plaster Creek Stewards Curb-Cut Rain Garden Social Impacts Study, Eleanor Vander Ark, Laura Luchies

Watershed Reports

As one method of minimizing pollutants in Plaster Creek, Plaster Creek Stewards (PCS) has installed Curb-Cut Rain Gardens (CCRGs) in the downstream neighborhoods of the Plaster Creek Watershed. CCRGs sit in the parkway between the sidewalk and the street, are planted with native plants, and have a cut in the curb to allow the influx of rainwater from the street. These gardens divert polluted rainwater from the creek by catching the water closer to where it falls and allowing it to filter into the ground.

As part of a grant from the Michigan Department of Environment, Great Lakes, and Energy …

Boiling Behind Bars: Exploring The Hidden Toll Of Extreme Heat On Mental Health In Texas Prisons, Sandra K. Miller

Social Work Theses - Archive

The State of Texas supports the largest prison system in the US and held 132,859 people in 100 units scattered across the state as of December 2023. Approximately 70% of Texas prison beds are not air conditioned, despite the state’s reputation for dangerously hot, humid summers. The State has officially recorded temperatures inside Texas prison facilities as high as 120 degrees with heat index values of over 150. Although there is a growing body of research on the negative physiological and psychological consequences of extreme heat among the general public, little is known about the physical and emotional toll of …

Quantum Dots' Toxicity: A Multi-Level Investigation On The Impact Of Quantum Dots On The Actin Cytoskeleton, Nhi Le

Graduate Theses/Dissertations

Quantum dots (QDs) are fluorescence nanomaterials with unique optical and physical properties. As such, they are highly sought after for their potential use in several biomedical and industrial applications. Despite their vast potential, recent studies have suggested that quantum dots are toxic to cells. Yet, the mechanism of quantum dots’ toxicity remains unclear. As such, my thesis aims to comprehensively examine the mechanism of quantum dots’ toxicity, emphasizing how quantum dots disrupt the actin cytoskeleton. In this study, I used RNA sequencing and mass spectrometry to investigate the influence of CdSe/ZnS QDs on the transcriptomic proteomic level of Saccharomyces cerevisiae …

Nanotoxicology Of Cdse/Zns Quantum Dot Alternatives In Thle-2 And Hepg2 Liver Cells, Seth Harris

Graduate Theses/Dissertations

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses an XTT viability assay, ROS fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS₂/ZnS, and carbon dots (NCD) in liver cells. The liver is a possible destination for accumulation of QDs making it an appropriate model for testing. A cancerous liver cell line known as HepG2, and an immortalized liver cell line known as THLE-2 were used. At …

Determining Perfluorooctanesulfonic Acid Adsorption On Nanoparticles Using Liquid Chromatography – Mass Spectrometry, Iqra Shakoor

Graduate Theses/Dissertations

The contamination of perfluorooctanesulfonic acid (PFOS, C₈F₁₇SO₃H) in water is considered a threat to humans and the environment. The strength of carbon and fluorine bond is responsible for its high stability in the environment. Therefore, it can be transferred from the environment to food sources and eventually humans. This study assessed the ability of nanoparticles to adsorb PFOS from water. The experiment was performed by preparing suspensions of PFOS (10 ppm) and different concentrations (1000 ppm, 500 ppm, 250 ppm) of cerium oxide nanoparticles (CeO₂-NPs) or magnesium oxide nanoparticles (MgO-NPs). The suspensions …

Effects Of Subchronic Oral Pfos Exposure Via Drinking Water On Gut Microbiota Composition, Emma Ann Loder

Graduate Theses/Dissertations

Perfluorooctanesulfonic acid (PFOS) has been phased out of production in the United States, but because of its resistance to degradation and its persistence in the environment, PFOS can be found in drinking water across America. Oral exposure to PFOS has been linked to adverse developmental, immunological, hepatic, and endocrine health. Oral PFOS exposure may alter the gut microbiota and cause dysbiosis, which is implicated in the pathology of inflammatory diseases like Crohn’s disease, diabetes, and ulcerative colitis. The goal of the study was to investigate the effects of subchronic oral PFOS exposure on the composition of the gut microbiota. Adult …

What Influences Trust In And Understanding Of Clinical Trials? An Analysis Of Information And Communication Technology Use And Online Health Behavior From The Health Information National Trends Survey, Aurora Occa, Allison S. Merritt, Allison Leip, Jerod L. Stapleton

UK CARES Faculty Publications

Background: Using information and communication technologies to seek, discuss, and share health-related information influences people’s trust and knowledge of several health practices. However, we know little about the associations between individuals’ information and communication technology use and their perceptions of trust and knowledge of clinical trials. Examining these associations may lead to the identification of target audiences and channels for developing effective educational interventions and campaigns about clinical trials.

Methods: In this study, we analyzed Health Information National Trends Survey data to document perceptions of clinical trial-related knowledge and trust that were recently added as questions in this annual national …

Evaluating Superfund Effectiveness And Community Engagement: Smurfit-Stone Mill Case Study, Abigail M. Sherwood

Undergraduate Theses, Professional Papers, and Capstone Artifacts

The Smurfit-Stone Mill operated in Frenchtown, MT from 1957 until 2010, releasing toxic pollutants into the Clark Fork River and surrounding areas. Despite environmental protests since the 1960s, substantive action to remedy environmental damage did not occur until 2015. Stakeholders including local residents, Indigenous tribes, Missoula County, and environmental non-profits have advocated for comprehensive site characterization, a timely cleanup, and robust community engagement. While residents and visitors contend with elevated toxins in fish tissue, prompting a 100-mile fish consumption advisory near the Smurfit-Stone Mill, the Environmental Protection Agency is several years away from determining the scope of a reclamation. Community …

Kvx-053, A Protein Tyrosine Phosphatase 4a3 Inhibitor, Ameliorates Sars-Cov-2 Spike Protein Subunit 1 - Induced Acute Lung Injury In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Tierney Day, Betsy Gregory, Elizabeth R. Sharlow, John S. Lazo, John D. Catravas

Bioelectrics Publications

The Acute Respiratory Distress Syndrome (ARDS), often preceded by acute lung injury (ALI), is characterized by the accumulation of inflammatory fluid in the lung alveoli, leaky alveolar epithelium and endothelium, and overexpression of pro-inflammatory cytokines. This progression from ALI to ARDS is a major contributor to the high mortality observed in COVID-19 patients. The Spike protein of SARS-CoV-2 binds to lung ACE2 and, in addition to facilitating viral cell entry, it plays an important role in the development of ALI and ARDS, especially in the later phases of COVID-19 as well as long COVID. Protein tyrosine phosphatase (PTP) 4A3 is …

Aggravated Ulcerative Colitis Via Circnlgn-Mediated Suppression Of Nuclear Actin Polymerization., William W Du, Chi Zhou, Hui Yang, Shuoyang Wen, Yu Chen, Eric X Chen, Xiuwei H. Yang, Feiya Li, Kevin Y Du, Hui Yuan, Ting Ye, Javeria Qadir, Burton B Yang

Pharmacology and Nutritional Sciences Faculty Publications

Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine, with its precise underlying causes remaining incompletely understood. In this study, we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis. Colitis patients produce significant higher levels of circNlgn. Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression, primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNlgn. Nlgn173 undergoes translocation into cell nuclei, where it interacts with actin, impeding the binding of actin-related protein 2 and 3 (Arp2/3) complex to …

Exposition Professionnelle Des Femmes Aux Substances Chimiques : Amélioration D’Une Matrice Emploi Exposition Existante Pour Fournir Des Estimations Spécifiques Au Sexe : Rapport Abrégé, Vikki Ho, Chelsea Almadin, France Labrèche, Mark Goldberg, Marie-Élise Parent, Jack Siemiatycki, Jérôme Lavoué

Rapports de recherche scientifique

Il est reconnu que les femmes et les hommes ont des profils professionnels différents qui peuvent donc se traduire par des risques de maladie professionnelle différents. Pourtant, la plupart de nos connaissances actuelles sur les maladies professionnelles découlent d'études menées auprès des hommes. Or, les femmes représentent actuellement 48 % de la population active au Québec. La santé des femmes dans l’environnement de travail demeure un domaine sous-étudié et nous sommes particulièrement freinés par le manque de compréhension de l'impact du genre sur l'exposition en milieu de travail. Il a été démontré que l'attribution des tâches et les conditions de …

Occupational Exposures Of Women To Chemical Substances: Improvement Of An Existing Job Exposure Matrix To Provide Sex-Specific Estimations Of Exposure, Vikki Ho, Chelsea Almadin, France Labrèche, Mark Goldberg, Marie-Élise Parent, Jack Siemiatycki, Jérôme Lavoué

Rapports de recherche scientifique

Il est reconnu que les femmes et les hommes ont des profils professionnels différents qui peuvent donc se traduire par des risques de maladie professionnelle différents. Pourtant, la plupart de nos connaissances actuelles sur les maladies professionnelles découlent d'études menées auprès des hommes. Or, les femmes représentent actuellement 48 % de la population active au Québec. La santé des femmes dans l’environnement de travail demeure un domaine sous-étudié et nous sommes particulièrement freinés par le manque de compréhension de l'impact du genre sur l'exposition en milieu de travail. Il a été démontré que l'attribution des tâches et les conditions de …

"It Is More Than A Feeling, It Is A Commitment" : Evaluation Of Empathy Development Using Graphic Novels In A Medical Humanities First-Year Seminar, Susanna Foxworthy Scott, Brittany R. Heer, Alli Leonard

Scholarship and Professional Work

No abstract provided.

(Plant)Ing Traditional Roots: Exploring An Impact Of Environmental Shifts On Traditional Phytotherapy Practices In The Cusco Region Of Perú, Nicole Elizabeth Wilmot

Undergraduate Honors Theses

This thesis investigates the potential outcomes of environmental shifts on plant-based medical practices in the Cusco region of Peru. Located in the Andes mountain range, at a high elevation, the environment varies immensely, specifically in the various types of native plants in the region. Historically, using plants as natural forms of medicine or healthcare has been deeply rooted in many indigenous communities, traditions, and cultures globally. Environmentally, there have been potential changes and shifts in temperature, water, and soil that affect the nutrition and health of plants to maintain their beneficial properties. Due to various factors, adaptations or shifts to …