Life Sciences Commons^™

Application Of Cytotoxicity Assays For Detection Of Potentially Harmful Bioactive Compounds Produced By Freshwater Bloom-Forming Algae, Jace Thomas Mclaughlin

Electronic Thesis and Dissertation Repository

Detection of harmful bioactive compounds produced by bloom-forming pelagic algae is important to assess the potential risks to communities. We applied two cell-based assays, an erythrocyte lysis assay (ELA) that assesses membrane integrity, and a RTgill-W1 cytotoxicity assay (RCA) that detects changes in cell metabolism, to evaluate the cytotoxic effects of: (1) individual toxins and noxious compounds; and (2) complex mixtures of compounds produced by cyanobacteria and chrysophyte isolates. ELA was insensitive to toxins and noxious compounds except at exceptionally high concentrations (EC₅₀≥10⁶ nM). RCA was sensitive to noxious compounds only, at concentrations greater than reported environmental …

Tremulous Jaw Movements Induced By The Vmat2 Inhibitor Tetrabenazine, Samantha J. Podurgiel

Master's Theses

Parkinsonism is a movement disorder characterized by several cardinal motor symptoms: resting tremor, akinesia, bradykinesia, rigidity, and postural instability. Parkinsonian resting tremor can be modeled in rodents using the tremulous jaw movement model. Tremulous jaw movements (TJMs) are defined as “rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus.” TJMs occur in a frequency range of 3-7 Hz and are induced by a number of pharmacological manipulations that parallel those seen in human Parkinsonism including dopamine (DA) depleting agents, DA antagonists, and cholinomimetic administration. Additionally, TJMs can be attenuated using antiparkinsonian …

The Role Of Drug Transporters In Statin-Induced Myopathy, Michael J. Knauer

Electronic Thesis and Dissertation Repository

Statins are the first line therapy for treatment and prevention of cardiovascular disease. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, reduce plasma cholesterol levels by inhibiting the rate-limiting step in cholesterol biosynthesis. While statins are well tolerated, up to 15% of patients develop myopathy, manifesting as muscle aches and pain and in rare cases, potentially life-threatening statin-induced rhabdomyolysis. Given that approximately 3 to 4 million Canadians are treated with statins, an estimated 500,000 patients experience associated skeletal muscle side effects that may prevent the continued treatment of hypercholesterolemia. Despite the prevalence of this side effect, little is known regarding …

Gene Expression Response In Early Developmental Stages Of Rainbow Trout Exposed To Ecologically Relevant Concentrations Of Malathion, Susan Miller

Theses and Dissertations

Understanding the early life stage toxic effects of environmental organophosphate exposure on organism health is crucial to identifying biomarkers that can be used for preventative care. Malathion, a potent organophosphate, is one of the most widely used organophosphates in agriculture and pest eradication. Due to its widespread use, pesticide runoff into area bodies of water poses a great threat to aquatic life and human inhabitants. Acute exposure to high concentrations of malathion causes neurological abnormalities and can result in respiratory failure, muscle spasms, and mental confusion in humans.

In the present study, the effects of malathion are observed following acute, …

Dreissena Rostiformis Bugensis: Desiccation Of Adult Quagga Mussels Found In Lake Mead As A Preventive Measure Against Overland Dispersal In The Western United States, Matthew Kappel

UNLV Theses, Dissertations, Professional Papers, and Capstones

The expansion of civilization across all borders of the world has proven to affect major components of ecosystems. Since the introduction and establishment of the aquatic invasive species (AIS),Dreissena rostiformis bugensis, commonly known as the quagga mussel, into the United States there has been an extensive amount of time and money spent on controlling and preventing their expansion across the United States. The quagga mussel is of major concern because of its ability to disrupt the ecological communities in previously non-infested bodies of water, which may cause a loss in biodiversity and effect environmental health. The quagga mussel has spread …

Evaluation Of The Tagelus® Ta 100d Sand Filter For Removing Quagga Mussel Veligers (Dreissena Rostriformis Bugensis) From Lake Water And The Effectiveness Of The Safeguard Ultraviolet Radiation System As A Biocide Against Veligers, Patricia Kathleen Delrose

UNLV Theses, Dissertations, Professional Papers, and Capstones

The Lake Mead National Recreational Area was created by the construction of the Hoover Dam during the years 1931-1936. In January 2007, the quagga mussel (Dreissena rostriformis bugensis), was found in Lake Mead. This became the first known Dreissenid species in the southwest and the only time a large water system was first infested by the quagga mussel and not the zebra mussel (Dreissena polymorpha). This invasive species has quickly spread to Lake Mohave and further down the lower Colorado River drainage. The microscopic size (70 µm or larger) of the veliger life stage makes it impossible to see with …

Intestinal And Hepatic Drug Transporters And Their Role In The Disposition Of Lipid-Lowering Drugs, Ute I. Schwarz

Electronic Thesis and Dissertation Repository

Membrane transporters are widely recognized for their role in drug disposition in humans. Differences in drug concentration among individuals for drugs used to treat cardiovascular diseases, such as statins and ezetimibe, may result from alteration in hepatic and intestinal transporter function due to genetic, clinical or environmental factors, causing variability in drug efficacy or toxicity.

The closely related uptake transporters organic anion-transporting polypeptides OATP1B3 and OATP1B1, are expressed in human liver sharing numerous drug substrates, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins. Recently, a transport-deficient OATP1B1 variant was associated with increased statin exposure and toxicity, however little is known regarding …

Cadmium Accumulation And Distribution In Lettuce And Barley, Fardausi Akhter

Electronic Thesis and Dissertation Repository

Cadmium (Cd) is a non-essential trace element and its environmental concentrations are increasing due to human activities. Edible plants can accumulate high concentrations of Cd, which could be toxic to humans. Understanding how and where Cd is stored in plants is important for ensuring lower concentration of Cd in the food. In this thesis, the accumulation and distribution of Cd in three agricultural plants, namely lettuce (Lactuca sativa L.), barley (Hordeum vulgare L.) and radish (Raphanus sativus L.), were investigated with a focus on the potential mechanisms involved in the localization of Cd in the root. The …

Human Equilibrative Nucleoside Transporter Subtype 1: Structure-Function Analysis Using Cysteine Mutagenesis And Thiol Modifying Techniques, Jamie Park

Electronic Thesis and Dissertation Repository

Human equilibrative nucleoside transporter 1 is the main mediator of bi-directional nucleoside flux and is found ubiquitously. Inhibitor and substrate interactions with ENT1 are known to be affected by cysteine-modifying reagents. Our aim was to investigate the importance of cysteine residues in hENT1 function and identify which residues were sensitive to thiol modification for further application of cysteine scanning mutagenesis on extracellular loop 5. Transporter function was assessed by the binding of [³H]NBMPR and the cellular uptake of [³H]2-chloroadenosine. Treatment of hENT1 with the neutral sulfhydryl-modifier methyl methanethiosulfonate (MMTS) enhanced [³H]NBMPR binding but decreased …

Statin Transport By Hepatic Organic Anion-Transporting Polypeptides (Oatps), Marianne K. Degorter

Electronic Thesis and Dissertation Repository

Drug transport proteins are important determinants of drug absorption, tissue accumulation, and elimination from the body, and there is growing appreciation for the contribution of altered drug transporter function to interindividual variability in drug response. The organic anion-transporting polypeptides (OATPs/SLCO) are uptake transporters with broad substrate specificity. Notably, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are commonly prescribed OATP substrates.

The OATP1B subfamily, expressed predominantly in the liver, is of particular importance to statins, which require hepatic entry to exert their low-density lipoprotein cholesterol lowering effect. We aimed to identify molecular determinants of substrate specificity in the …

Superfund Evaluation: The Families Of Tar Creek, Gary D. Wilson

Graduate Theses and Dissertations

The Tar Creek Superfund Site is located in far northeastern Oklahoma near the Oklahoma/Kansas border in Ottawa County. The Site generally consists of a forty-square-mile area which is also part of the larger Tri-State Mining District that includes areas of Kansas and Missouri. The Site includes parts of five communities: Picher, Cardin, Quapaw, North Miami, and Commerce in Oklahoma. It also includes Treece, Kansas, and affects a total population of roughly 30,000 residents. Following Superfund designation, families in the Tar Creek area had to decide whether to accept or reject buy-out offers. This project explored the decision-making processes employed by …

Continental-Scale Characterization Of Molecular Variation In Quaking Aspen, Colin M. Callahan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Quaking aspen has the largest natural distribution of any tree native to North America, ranging from Alaska through the breadth of Canada and south to mid-Mexico. Recent studies suggest a general decline of aspen throughout much of the range since at least the mid-20th century, though these findings remain inconclusive. Regardless, factors such as climate change, periods of drought, soil nutrient deficiencies, pathogens, insects, and encroachment by other tree species all pose risks to the health and maintenance of aspen across the continent. This situation is exemplified in the western United States where climate change is forecasted to have an …

Application Of Multivariate Statistical Methodology To Model Factors Influencing Fate And Transport Of Fecal Pollution In Surface Waters, Kimberlee K. Hall

Electronic Theses and Dissertations

Degraded surface water quality is a growing public health concern. While indicator organisms are frequently used as a surrogate measure of pathogen contamination, poor correlation is often observed between indicators and pathogens. Because of adverse health effects associated with poor water quality, an assessment of the factors influencing the fate and transport of fecal pollution is necessary to identify sources and effectively design and implement Best Management Practices (BMPs) to protect and restore surface water quality. Sinking Creek is listed on the State of Tennessee’s 303D list as impaired due to pathogen contamination. The need to address the listing of …

Analysis Of Nanoparticle Exposure On Legionella Pneumophila Biofilm Morphology And Host-Bacteria Interactions, Tara Diane Raftery

All Theses

An increase in the amount of money spent on nanotechnology has led to an increase in funding to support nanoparticle (NP) research. Due to their stable, beneficial properties, NPs are found in daily consumer products such as bike frames, socks, cosmetics, and sunscreens. As a result of this, these NPs have the potential to enter the environment and interact with various organisms that play integral roles in the ecosystem as a whole. The effect that NPs have on aquatic systems is largely unknown and understudied. Biofilms are an important structural and functional part of aquatic ecosystems, and comprise various microorganisms …

Unintentional Home Injury Risks Among The Elderly In Southern Nevada, Michelle Echauz Ching

UNLV Theses, Dissertations, Professional Papers, and Capstones

The elderly population (65 years of age and older) is one of the fastest growing populations in the US. A major public health concern involving the elderly population is unintentional injuries in the home. Since elderly adults typically spend the majority of their time in the home, minimizing unintentional home injury hazards is crucial for this population. The Nevada Healthy Homes Partnership (NHHP) program is a grant funded effort that helps to improve the quality and availability of safe and healthy homes in Nevada. Therefore, the purpose of this study is to determine the effectiveness of the NHHP program interventions …

The Role Of Grk2 In Hypertension And Regulation Of Gpr30, Bonan Liu

Electronic Thesis and Dissertation Repository

In the hypertensive state, the expression of G protein-coupled receptor kinase 2 (GRK2) level is elevated. On the other hand, the expression of GPR30, a recently discovered GPCR is greatly impaired. The current study focuses on investigating the roles of these two proteins in regulating G protein signaling under the normal and hypertensive states. Angiotensin II and vasopressin were used to examine the effects of GRK2 on G_q coupled GPCR signaling. ERK phosphorylation was proportionally enhanced with GRK2 over-expression. On the other hand, using arborization and wrinkle assays, I have shown that GRK2 acts as a negative regulator of …

Characterization Of Eif2be And Its Interaction With Rgs2, William H. Xue

Electronic Thesis and Dissertation Repository

RGS2 is a GTPase accelerating protein for Gαq and its expression can be upregulated in response to different types of stress. We recently showed that RGS2 can bind to the translation initiation factor, eIF2Bε, and decrease global protein synthesis. The objective of this study is to characterize the RGS2 binding domain of eIF2Bε, and investigate the functional consequences as a result of their interaction. To identify the RGS2 binding domain of eIF2Bε, I generated various truncated eIF2Be-GST fusion proteins and used them in an in vitro pulldown assay. The results of my study revealed that the binding domain lies within …

Correlation Of In-Vitro Drug Dissolution And In-Vivo Drug Absorption Of Various Therapeutically Equivalent Pharmaceutical Solid Dosage Forms Of Simvastatin, Aphrodite Kotrotsios

PCOM Biomedical Studies Student Scholarship

Simvastatin is a well known anti-cholesterol drug that is commercially available in the United States in various strengths including Simvastatin Tablets, USP 80 mg, that are under the brand name Zocor (manufactured by Merck Pharmaceutical Co.) and various generic equivalent products for example those manufactured by Teva Pharmaceuticals, Inc. and Dr. Reddy’s Laboratories, Ltd. When generic products are tested in the United States, they must be found to be equivalent with their branded products by the FDA. Therefore, generic Simvastatin Tablets, USP 80 mg, have been tested and approved by the FDA as equivalents to, and substitutable with, the branded …

The History Of Mining In Cerro De Pasco And Heavy Metal Deposition In Lake Junin Peru, Erin M. Delman

Honors Theses

Lake Junín covers 530-km2 and is located at 4,430-m in an intermontane basin between the eastern and western cordillera of the central Peruvian Andes. The lake sits between the large sulfide mining districts of La Oroya and Cerro de Pasco. Designated a National Reserve in 1974, Lake Junín drains northward to the Río San Juan, which joins the Río Mantaro within several kilometers of the lake. Dam construction by the Cerro de Pasco Copper Corporation on the Río Mantaro in 1932 caused the Río San Juan, the principal river draining Cerro de Pasco, to back up into the lake. Using …

Documenting The Anthropogenic Impact On Ballston Lake New York From A Short Core Using Stable Isotopes Of Carbon And Nitrogen And Trace Metals, Taylor S. Labrecque

Honors Theses

Ballston Lake occupies a portion of an avulsed channel of the Mohawk River between Schenectady and Saratoga Springs, New York. The lake is about 5 km long, generally less than 200m wide, ~8-15m deep, dimictic, with a catchment basin area of ~22km2. Long cores (>8 m) indicate that the lake formed ~13,000 cal yr BP. This study was undertaken to document recent environmental change recorded in the upper portion of sediment in Ballston Lake. Three sediment cores ~40 cm long were acquired from ~8 m water depth at the north end of Ballston Lake (42°57.101’N, 73°51.066’W), and were analyzed …

Environmental Monitoring Of Chemicals In Swimming Pools In North And Northeast Houston, Ogochukwu Adaikpoh

Theses (Pre-2016)

N/A

San Antonio High School Food Justice Program: A Handbook And Evaluation Of Edible Education, Katherine B. Tenneson

Pitzer Senior Theses

This senior environmental studies thesis explains and analyzes edible education through a food and gardening program at a continuation high school in Claremont, California. The first chapter situates the program-specific analysis by providing background information of the edible education movement, a history of the Edible Schoolyard in Berkeley, California, and an explanation of why food is a powerful teaching tool. The second chapter delineates the program by describing all of its components and compiling essential resources and teaching documents. The third chapter is based on interviews with 9 of 12 involved students and 7 teachers, and thoroughly explains the outcomes …

Localization And Expression Of Gfrα2 Receptors In Neonatal And Adolescent Mouse Heart., Bryan Gunter

Undergraduate Honors Theses

Neurturin (NRTN), a member of the glial cell-line derived neurotrophic factor(GDNF) family, is required in the development of parasympathetic cholinergic neurons. It signals through binding to a glycosyl-phophatidyl inositol (GPI)-linked receptor, GDNF family receptor α2 (GFRα2), which couples to Ret tyrosine kinase. Studies of NRTN knockout mice have shown that NRTN is essential for normal cholinergic innervation of the heart, but the precise role of NRTN remains unknown. For NRTN to evoke a biological response, GFRα2 must be localized to the surface of target neurons. The aim of this study was to determine the expression and localization of GFRα2 at …

A Factor Analysis Of The Health, Safety, And Welfare In The Built Environment Toward Interior Design As Perceived By Building Industry Professionals, Dana Marie Moody

Doctoral Dissertations

This research study created, piloted, and field tested a new instrument designed to collect perceptions toward an interior designer’s impact on the health, safety, and welfare of the public. It also established an initial profile of perceptions within building industry professionals, identified the salient factors within those perceptions, and determined the level of these factors through a factor analysis. The Health, Safety, & Welfare in the Built Environment instrument was developed using a Table of Specifications based on the subject content that interior designers must be familiar with in regards to protecting the health, safety, and welfare of the public …

Effects Of Maternal Low Protein Diet On Expression Of Drug Transporters In The Blood-Brain Barrier Of Adult Offspring, Bonnie L. Hastings

Senior Theses

Adverse uterine environment, manifested as low birth weight (LBW), has been shown to predispose individuals to hypertension, diabetes, and obesity by mechanisms that are just beginning to be understood. One of the mechanisms is the dysregulation of the expression or function of drug transport proteins, such as the organic anion transporter (OAT) family, which are crucial for the transport of various endogenous and exogenous compounds into and out of all organs, especially the brain. Hence, we examined the status of select drug transporters in the blood-brain barrier (BBB), using a LBW rat model. Maternal low protein diet (LPD) during gestation …

A Pre-Clinical Assessment Of Minocycline For Treatment Of Chronic Neuropathic Pain After Spinal Cord Injury, Alissa R. Poteete

Dissertations & Theses (Open Access)

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP.

Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment …

Arsenic Contamination In Groundwater In Vietnam: An Overview And Analysis Of The Historical, Cultural, Economic, And Political Parameters In The Success Of Various Mitigation Options, Thuy M. Ly

Pomona Senior Theses

Although arsenic is naturally present in the environment, 99% of human exposure to arsenic is through ingestion. Throughout history, arsenic is known as “the king of poisons”; it is mutagenic, carcinogenic, and teratogenic. Even in smaller concentrations, it accumulates in the body and takes decades before any physical symptoms of arsenic poisoning shows. According to the World Health Organization (WHO), the safe concentration of arsenic in drinking water is 10 µg/L. However, this limit is often times ignored until it is decades too late and people begin showing symptoms of having been poisoned.

This is the current situation for Vietnam, …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations & Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations & Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

Evaluation Of Urinary Pesticide Biomarkers Among A Sample Of The Population In The United States, Alex Lance Lebeau

USF Tampa Graduate Theses and Dissertations

Pesticide use in the United States continues to attract negative public attention. In recent years, this attention has focused on the effects that chronic, low-level pesticides may have, especially on children and various sub-populations. Over the past decade, studies have attempted to correlate negative health effects with detections of pesticide biomarkers in biological media. The current research investigates biomarker of exposure levels in a sample of the United States population. Data from the 2001-2002 NHANES dataset (n=11,039) was evaluated. The detection frequency of urinary biomarkers of exposure and the geometric mean from the NHANES pesticide dataset (n=3,152) were determined. Of …