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Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell 2018 East Tennessee State University

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years ...


A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin 2018 University of Louisville

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and inflammation, along ...


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle 2018 University of Louisville

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...


Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller 2018 University of Louisville

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug ...


Egfr Signaling From The Early Endosome., Julie A. Gosney 2018 University of Louisville

Egfr Signaling From The Early Endosome., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue ...


Antimicrobial Efficacy And Safety Of A Novel Gas Plasma-Activated Catheter Lock Solution, Sudhir Bhatt, Poonam Mehta, Chen Chen, Dayle A. Daines, Leonard A. Mermel, Hai-Lan Chen, Michael G. Kong 2018 Old Dominion University

Antimicrobial Efficacy And Safety Of A Novel Gas Plasma-Activated Catheter Lock Solution, Sudhir Bhatt, Poonam Mehta, Chen Chen, Dayle A. Daines, Leonard A. Mermel, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 ...


Macrophytes And Atrazine In Ponds Of Southwest Missouri, Christine Michelle Cornish 2018 Missouri State University

Macrophytes And Atrazine In Ponds Of Southwest Missouri, Christine Michelle Cornish

MSU Graduate Theses

Wetlands are often the ultimate destination of agrochemicals. The increased use of these pollutants has resulted in their increased transport, via runoff and spray drift, into wetlands. Atrazine, a commonly used herbicide, has been detected in surface water, groundwater, soil, and sediment, and has shown to have adverse impacts on aquatic biota, such as fish and amphibians. Few studies have reported on the relationships between atrazine and macrophytes. I measured atrazine concentrations in surface sediments in agricultural, conservation, and golf course ponds of southwest Missouri, and investigated how those concentrations might be related to macrophyte communities, and pond environmental characteristics ...


Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin 2018 University of Kentucky

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and ...


Role Of Mcp-1 And Ccr2 In Ethanol-Induced Neuroinflammation And Neurodegeneration In The Developing Brain, Kai Zhang, Haiping Wang, Mei Xu, Jacqueline A. Frank, Jia Luo 2018 University of Kentucky

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Neuroinflammation And Neurodegeneration In The Developing Brain, Kai Zhang, Haiping Wang, Mei Xu, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Background: Neuroinflammation and microglial activation have been implicated in both alcohol use disorders (AUD) and fetal alcohol spectrum disorders (FASD). Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. FASD is the leading cause of mental retardation, and one of the most devastating outcomes of FASD is the loss of neurons in the central nervous system (CNS). The underlying molecular mechanisms, however, remain unclear. We hypothesize that MCP-1/CCR2 signaling mediates ethanol-induced neuroinflammation and microglial activation, which exacerbates neurodegeneration in the developing brain.

Methods: C57BL/6 ...


Effects Of The Everyday Toxin, Titanium Dioxide, On Drosophila Melanogaster Nervous System Development, Maria Carparelli, Kelsey Ripley, Stefanie Otto-Hitt 2018 Carroll College

Effects Of The Everyday Toxin, Titanium Dioxide, On Drosophila Melanogaster Nervous System Development, Maria Carparelli, Kelsey Ripley, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

Titanium dioxide (TiO2) is a widely used compound found in everything from food packaging to sunscreens. When ingested, TiO2 is readily transported across membranes and efficiently stored within cells. Previous studies showed that exposure to TiO2 results in underdeveloped nervous systems. For our study, we attempted to answer the following question: Will exposing Drosophila melanogaster larvae to TiO2 affect expression of the Neur gene and development of the central nervous system? The Neur gene is crucial during the celldetermination stage of development as its encoded protein helps specify neuroblast development and aids in nervous system and sensory organ development. It ...


The Effect Of Imidacloprid On Honey Bee Queen Fecundity, Jamilyn Martin, Julia D. Fine, Amy Cash-Ahmed, Gene E. Robinson 2018 Kaskaskia College

The Effect Of Imidacloprid On Honey Bee Queen Fecundity, Jamilyn Martin, Julia D. Fine, Amy Cash-Ahmed, Gene E. Robinson

PRECS 2018

Imidacloprid is a neonicotinoid insecticide commonly used in agricultural settings to control insect pests by acting as an agonist of acetylcholine receptors and inducing paralysis and mortality. In small doses, imidacloprid can cause loss of memory and foraging ability along with impaired learning and a lowered immune response in western honey bees (Apis mellifera). Effects of neonicotinoid insecticides on colony reproduction have been documented including decreased colony expansion, queen failure and replacement, and decreased queen egg laying.

For this study, we examined the effects of imidacloprid on the fecundity of queen bees when their worker attendants were exposed to low ...


Effects Of Sulfur Dioxide On Abda Gene Expression And Larval Development In Drosophila Melanogaster, Emma Esposito, Keenan McNally, Stefanie Otto-Hitt 2018 Carroll College

Effects Of Sulfur Dioxide On Abda Gene Expression And Larval Development In Drosophila Melanogaster, Emma Esposito, Keenan Mcnally, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

In this experiment, we tested the effects sulfur dioxide exposure had on abd-A gene expression and larval development in Drosophila melanogaster. Previous studies showed that sulfur dioxide exposure inhibits development of gonads in adult flies and increases development time. We hypothesized that expression of abd-A would decrease in developing Drosophila exposed to sulfur dioxide. The abd-A gene is in the Hox gene family, which functions in the development of body segmentation. The abd-A gene is specific to the abdominal region of the fly, and is also important to the development of gonads and fat bodies. To test our hypothesis, we ...


Effect Of Potassium Bromate On Oxr1 Gene Expression And Cell Growth In Tetrahymena Thermophila, Scott Khale, Brendan McMahon, Stefanie Otto-Hitt 2018 Carroll College

Effect Of Potassium Bromate On Oxr1 Gene Expression And Cell Growth In Tetrahymena Thermophila, Scott Khale, Brendan Mcmahon, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

The purpose of our experiment was to answer the question: Does oxidative damage, induced by potassium bromate (KBrO3), affect growth rate and expression of the OXR1 gene in Tetrahymena thermophila? Potassium Bromate was chosen as the environmental stressor because it is a strong oxidizing agent that is used as a leavening agent in baked goods. It was hypothesized that expression of OXR1 would increase in Tetrahymena cells that were exposed to potassium bromate and that their growth rate would decrease. The exact mechanism and function of the OXR1 gene is still unknown; however, the literature suggests that it is required ...


Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen 2018 University of Nebraska-Lincoln

Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen

Chemical and Biomolecular Engineering -- All Faculty Papers

In this study, heparin-loaded poly-ε-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was ...


Manganese Toxicity In The Dopamine Synthesis Pathway In Drosophila Melanogaster, Brandon Adair, Tamra E. Jones, Stefanie Otto-Hitt 2018 Carroll College

Manganese Toxicity In The Dopamine Synthesis Pathway In Drosophila Melanogaster, Brandon Adair, Tamra E. Jones, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

Manganese is prevalent in Montana, and Manganese toxicity symptomatically resembles Parkinsons disease. The goal of this project was to determine whether exposure to high levels of Manganese affects the Dopamine synthesis pathway. For our experiment, we chose to measure the expression of the ple gene in Drosophila melanogaster that were exposed to Manganese during development. The ple gene codes for Tyrosine Hydroxylase, an enzyme that functions in the first rate-limiting step of Dopamine synthesis. We hypothesized that an abundance of Manganese would result in decreased expression of ple in larvae and observable motor function deficits among adult flies. To carry ...


The Effect Of Metal Pollutants On Cell Growth And Ttherm0058490expressionint Etrahymenathermophila, Inderbir Bains, William French, Stefanie Otto-Hitt 2018 Carroll College

The Effect Of Metal Pollutants On Cell Growth And Ttherm0058490expressionint Etrahymenathermophila, Inderbir Bains, William French, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

In this experiment, we sought to answer the following question: Do higher levels of metal exposure affect expression of the TTHERM 00584900 gene in Tetrahymena thermophila? The TTHERM 00584900 gene produces an ATP-binding cassette protein that is responsible for removing metals and metalloids from Tetrahymena thermophila. It is hypothesized that the expression of TTHERM 00584900 will increase with exposure to metals. In order to test this hypothesis, Tetrahymena thermophila were randomly assigned to either a control group, which was cultured in a normal growth medium, or a treatment group, whichin addition to the medium was exposed to water contaminated with ...


Effect Of Nitrate Pollution On Tetrahymena Thermophila, Reegan DeBruycker, Hannah Sylvester, Stefanie Otto-Hitt 2018 Carroll College

Effect Of Nitrate Pollution On Tetrahymena Thermophila, Reegan Debruycker, Hannah Sylvester, Stefanie Otto-Hitt

Life and Environmental Sciences Course-based Research Projects

The question under investigation in this project was: Does an elevated concentration of nitrates have a negative eect on cell growth and expression of the CDC16 gene in the organism Tetrahymena thermophila? Exposure of Tetrahymena cultures to nitrates mimics the exposure of these organisms to nitrate pollution in the environment, which can occur due to septic tank leakage, nitrogen-rich fertilizer run o, and agricultural processes. The EPA standard for nitrate concentrations in drinking water is a maximum of 10ppm. In our experiment, Tetrahymena cultures were treated with media that contained 30ppm of nitrates for one week. The 30ppm nitrate concentration ...


Variation In Airborne Pollen Concentrations Among Five Monitoring Locations In A Desert Urban Environment, Tanviben Y. Patel, Mark P. Buttner, David Rivas, Chad L. Cross, Dennis A. Bazylinski, Joram S. Seggev 2018 University of Nevada, Las Vegas

Variation In Airborne Pollen Concentrations Among Five Monitoring Locations In A Desert Urban Environment, Tanviben Y. Patel, Mark P. Buttner, David Rivas, Chad L. Cross, Dennis A. Bazylinski, Joram S. Seggev

Environmental & Occupational Health Faculty Publications

The urbanization of the Las Vegas Valley has transformed this part of the Mohave Desert into a green oasis by introducing many non-native plant species, some of which are allergenic. Typically, one monitoring station is established per city to obtain pollen counts for an entire metropolitan area. However, variations in pollen concentrations could occur among different microenvironments. The objective of this study is to measure and compare pollen concentrations in five locations in Las Vegas to determine if there are significant differences between microenvironments within the city. Air samples were collected from five sites across the Las Vegas Valley over ...


Developing Ocean Color Algorithm Using Moderate Resolution Imaging Spectroradiometer (Modis) Sensor For Shallow Coastal Water Bodies, Mohd Manzar Abbas 2018 Florida International University

Developing Ocean Color Algorithm Using Moderate Resolution Imaging Spectroradiometer (Modis) Sensor For Shallow Coastal Water Bodies, Mohd Manzar Abbas

FIU Electronic Theses and Dissertations

This study analyses the spatial and temporal variability of chlorophyll-a in Chesapeake Bay; assesses the performance of Ocean Color 3M (OC3M) algorithm; and develops a novel algorithm to estimate chlorophyll-a for coastal shallow water. The OC3M algorithm yields an accurate estimate of chlorophyll-a concentration for deep ocean water (RMSE=0.016), but it failed to perform well in the coastal water system (RMSE=23.17) of Chesapeake Bay. A novel algorithm was developed which utilizes green and red bands of the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. The novel algorithm derived the chlorophyll-a concentration more accurately in Chesapeake Bay (RMSE ...


Anti-Tumor Activity Of Phenoxybenzamine And Its Inhibition Of Histone Deacetylases, Mario A. Inchiosa 2018 New York Medical College

Anti-Tumor Activity Of Phenoxybenzamine And Its Inhibition Of Histone Deacetylases, Mario A. Inchiosa

NYMC Faculty Publications

The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several "off label" indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact ...


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