Life Sciences Commons^™

Exploring Knowledge, Beliefs And Practices Of Radon Gas Exposure Among Public Health Workers, Paschal Nwako

Seton Hall University Dissertations and Theses (ETDs)

Radon gas exposure is the highest cause of lung cancer among people that never smoked in the United States. People exposed to elevated levels of radon had a higher risk of developing lung cancer. Achieving the long term goal of the Indoor Radon Abatement Act (IRAA) of 1988 require a combined efforts of government agencies. Public health workers are change agents and their role in protecting and improving the health of their communities are well documented. This study created and utilized a multi question survey, the Public Health Workers Radon Assessment Instrument (PHWRAI) to explore knowledge, beliefs, personal and professional …

New Insights Into Signal Detection Of The Effects Of Exposures During Pregnancy, Fatma Etwel

Electronic Thesis and Dissertation Repository

There is inadequate information on the fetal safety of drugs during pregnancy for the majority of marketed drugs. It is challenging to examine the safety and efficacy of drugs during pregnancy due to the ethical issues of exposing unborn babies to these chemicals. It often takes many years before associations between a drug and its safety, efficacy, and toxicity in pregnancy can be established. This thesis will examine strategies in signal detection of the effects of drug exposures during pregnancy.

Meta-analyses have become useful in the area of clinical teratology. Observational studies provide the main source of information in these …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Nanoparticle Toxicity And Molecular Mechanisms In Fish: A Case Study With Silver Nanoparticles, Jiejun Gao

Open Access Dissertations

Nanoparticles (NPs) are widely used in a myriad of commercial and industrial products making their entry to the environment a likely event. NPs have unique physical-chemical properties that result from their small size and high surface area to volume ratio, making them highly reactive and potentially toxic. In Chapter 1, we summarize the effects and mechanisms of metal-based NPs on the vascular system. In vitro studies have shown that NPs are anti-angiogenic because they cause inflammation, oxidative stress, and apoptosis of endothelial cells resulting in increased permeability and decreased proliferation and migration. Whole animal studies examining the effects of NPs …

Gonadal Intersex In Teleosts: Mechanisms, Molecular Biomarkers And Diagnostic Assays, Ahmed M.E. Abdel-Moneim Mohamed

Open Access Dissertations

Natural and synthetic estrogenic and androgenic compounds are continuously released into aquatic ecosystems. Exposure of teleost fishes to these contaminants can negatively impact sex differentiation and reproductive output. Specifically, development of gonadal intersex in gonochoristic (fixed sex) fish species has been studied extensively in relation to exposure to this class of compounds. The main objectives of this dissertation were to: 1) conduct field and laboratory studies to investigate the molecular signaling pathways behind the development of gonadal intersex; and 2) establish molecular biomarkers and assays for testing the ability of environmental pollutants to develop this condition using a battery of …

The Relationship Between Lead In Groundwater And Elementary School Students' Academic Performance In Missouri, Lynnette Xiangling Li

MSU Graduate Theses

Lead exposure can come from various sources, e.g., lead mines, industrial areas, and lead based paint. Missouri has more than 4,128 lead mines. Lead is a neurotoxin. The objectives of the study were to investigate i) the spatial relationship between lead mines and lead distribution in groundwater, ii) the statistical impact of lead in groundwater on students' Missouri Assessment Program (MAP) scores, and iii) the geographic variations of lead's impact on students' MAP scores. Geographic Information Science spatial analysis tools were used to analyze the concentration of lead in groundwater within school districts in Missouri. Regression analysis was utilized to …

Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted

Electronic Theses and Dissertations

Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as well as determine target tissue concentration. These included the …

Using Mouse Models To Define How The P53 R72p Polymorphism Impacts The Adverse Effects Of Doxorubicin And Ionizing Radiation, Emily Dominguez

Dissertations & Theses (Open Access)

The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene p53 codes for either an arginine (R) or proline (P) (p53 R72P). This SNP may impact how cells respond to genotoxic insult. Studies in cell culture and in tissues from mouse models of the SNP indicate that, in response to gentoxic treatment, the two variants may differentially induce apoptosis and expression of p53 target genes. In epidemiological studies, the P variant is associated with decreased cancer survival and increased risk of side-effects from genotoxic cancer treatment. Genotoxic therapy is still the mainstay of cancer treatment, and doxorubicin …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

Determining The Effects Of The Think Risk Initiative As Implemented By The Southern Nevada Health District, Karalin Nichole Cronkhite

UNLV Theses, Dissertations, Professional Papers, and Capstones

In the United States, someone becomes infected with a foodborne illness every 2 seconds, is hospitalized by a foodborne illness every 4 minutes and dies due to a foodborne illness every 3 hours. Foodborne illness is preventable, yet each year, 1 in 6 Americans is affected by it from contaminated foods or beverages. There are over 250 different foodborne diseases, and in 2015, there were 73 confirmed cases of Salmonella infection in Southern Nevada alone. Since the emergence of public health, food establishment inspections have been an important part of the regulation of food safety. Risk-based inspections were developed by …

Analysis Of Synthetic Cannabinoids And Drugs Of Abuse Amongst Hiv-Infected Individuals, Jillian M. Wetzel

Student Theses

Synthetic cannabinoids are man-made mind-alternating chemicals. Law enforcement and legislation have attempted to classify many of these synthetic cannabinoids as schedule I controlled substances, however, they are continuously being modified by dealers at the retail end of the distribution chain. Addiction and moderate use of illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy among HIV patients. However, there is no data regarding the impact of synthetic cannabinoid exposure in this population and how this affects their compliancy with taking antiretroviral therapy. A total of 72 authentic urine specimens were collected weekly from 13 individuals with …

The Importance Of Serotonergic And Adrenergic Receptors For The Induction And Expression Of One-Trial Cocaine-Induced Behavioral Sensitization, Krista N. Rudberg

Electronic Theses, Projects, and Dissertations

Addiction is a complex process in which behavioral sensitization may be an important component. While the behavioral effects of sensitization are well established, the intricate neurobiology of the phenomenon is still largely unknown. Dopamine systems mediate the induction of behavioral sensitization in adult rats, but there is a large amount of evidence showing that other neurotransmitter systems also modulate the induction process. For example, the α1b-adrenergic and 5-HT_2A receptor systems are known to modulate the sensitized responding of adult rats, but the roles that these receptor systems play in the induction and expression of behavioral sensitization during the preweanling …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …

Hormone Replacement Therapy (Hrt) Modulates Peripheral And Central Auditory System Processing With Aging, Tanika Williamson

USF Tampa Graduate Theses and Dissertations

After the findings were reported for the Women’s Health Initiative (WHI) study in the past decade, there has been a significant decline in the overall use of hormone replacement therapy (HRT) among women. However, there are still millions of middle-aged, menopausal women in the U.S. who are currently undergoing hormone therapy. Their reasons for continuing treatment include relief of severe menopausal symptoms, aid in the management of osteoporosis and reduction in the risk of colon cancer (Ness et al., 2005). The purpose of the following investigation was to evaluate the impact of HRT on the central and peripheral auditory systems …

Effects Of Antibiotic Mixtures Across Marine Intertidal Trophic Levels: Examining Environmentally-Relevant Contaminant Concentrations, Jaclyn Rebecca Teixeira

Dissertations and Theses

Approximately 48% of Americans use prescription drugs within each 30-day period, and there are signs this trend is increasing. Although many studies track pharmaceuticals’ fates in contaminating waterways, only fairly recent efforts have examined the potential impacts of these drugs on non-target organisms. The antibiotics sulfamethoxazole and trimethoprim, often prescribed together to treat bacterial infections, have been detected worldwide in marine and estuarine environments at concentrations up to 700-800 ng/L each. Toxic effects of these drugs have been identified in freshwater organisms, with synergistic effects observed in short-term studies of mixtures of the two; however, little research has examined possible …

The Influence Of Oxygen Tension And Glycolytic And Citric Acid Cycle Substrates In Acrolein-Induced Cellular Injury In The Differentiated H9c2 Cardiac Cell Model, Jayme Coyle

USF Tampa Graduate Theses and Dissertations

Most in vitro systems employ the standard cell culture maintenance conditions of 95 % air with 5 % CO2 to balance medium pH, which translates to culture oxygen tensions of approximately 20 % - above the typical ≤ 6 % found in most tissues. The current investigation, therefore, aims to characterize the effect of maintenance and toxicant exposure with a particular focus on the α,β-unsaturated aldehyde, acrolein, in the presence of physiologically relevant oxygen tension using a differentiated H9c2 cardiomyoblast subclone. H9c2 cells were maintained separately in 20.1 and 5 % oxygen, after which cells were differentiated for five days, …

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR₁ and 5-HT_2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT_2A/CRs. The first purpose of this thesis was …

Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux

Electronic Thesis and Dissertation Repository

CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in inducible U2OS Flp-In …

Quantifying The Toxicity Of 1-Methylnaphthalene To The Shallow-Water Coral, Porites Divaricata, For Use In The Target Lipid Model, Nicholas Turner

HCNSO Student Theses and Dissertations

The proximity of coral reefs to coastal urban areas and shipping lanes predisposes corals to petroleum pollution from multiple sources. Previous research has evaluated petroleum toxicity to coral using a variety of methodologies, including monitoring effects of acute and chronic spills, in situ exposures, and ex situ exposures with both adult and larval stage corals. Variability in toxicant, bioassay conditions, species and other methodological disparities among studies prevents comprehensive conclusions regarding the toxicity of hydrocarbons to corals. This research evaluated the 48-hour toxicity of 1-methylnaphthalene to Porites divaricata using a continuous-flow passive dosing system. The range-finding exposure evaluated the dosing …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Molecular Mechanisms Involved In Neurotoxicity Mediated By Hiv Proteins And Drug Abuse, Yu Cai

Theses & Dissertations

While the advancement of highly active antiretroviral therapy (HAART) has transformed the course of HIV/AIDS from a death sentence to a manageable chronic condition, the prevalence of a constellation of neurological disorders collectively termed as HIV-associated neurocognitive disorders (HAND) continues to persist in these patients. HAND is characterized by cognitive dysfunction, depression, impaired memory and/or deficits in motor skills. The underlying factors leading to HAND have been the subject of extensive research and are thought to be associated with HIV infection in the CNS combined with robust immune activation of resident cells of the CNS. In addition, there is a …

X-Ray Fluorescence For Quantification Of Lead And Strontium In Vivo, Aaron James Specht

Open Access Dissertations

Lead (Pb) is a toxicant well known for its effects on almost every organ system in the body. Pb use in industry has declined since removal of Pb from gasoline, but many developing countries still have significant use of Pb. Exposure to Pb has been linked with diseases causing neurodegeneration and thus have lasting effects long after the initial exposure. Another metal, strontium (Sr), has been linked with bone disease in particular situations and shown to have uses in treating osteoporosis as a supplement. However, there are no studies of the effects of Sr using a meaningful biomarker. The most …

Manufacturer Perspectives On Content Transparency And Material Health In The Us Building Products Industry, Alexandra A. Muller

Open Access Theses

Flawed U.S. federal regulation of chemicals has resulted in a materials market that undervalues human and environmental health in favor of the more traditional attributes of price, performance and aesthetics. In the building products industry, global, dynamic supply chains and proprietary information concerns further complicate the task of assessing the material health of products.

Voluntary material health programs in the green building industry are intended to incentivize the manufacture and selection of safer products by getting companies to gather and assess ingredient, hazard and risk information from their supply chain. Building product manufacturers considered early adopters of the main material …

The Interactive Effects Of Pesticide Exposure And Infectious Disease On Amphibian Hosts, Katherine M. Pochini

Open Access Theses

Natural systems are home to a multitude of natural and anthropogenic stressors, which draw an array of effects on ecological communities. While these effects have been investigated individually, it is important, given the routine co-occurrence of these stressors, to understand their interactive effects. Pesticide exposure and infectious disease are two common, co-occurring stressors that each have documented detrimental effects on species and, as evidence suggests, may have interactive effects. Moreover, existing research suggests that these interactive effects are highly context dependent, eliciting different results based on species, disease agent, toxin, and environment. Given the variability with which species may experience …

Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various …

The Role Of The Nucleolus In Neurodegeneration., Justin Lauren Hallgren

Electronic Theses and Dissertations

The overarching goal of my studies was to determine the role of the nucleolus in neurodegenerative disease. Numerous studies suggest the impairment of ribosomal biogenesis in neurodegenerative disease and such a condition may contribute to neuronal dysfunction in two ways, loss of function and stress response. Ribosomal biogenesis has been demonstrated to play an essential role in both neuronal growth and maintenance. Therefore insufficient levels of ribosomal biogenesis would be expected to produce atrophy and synapse loss. Moreover, the fidelity of ribosomal biogenesis is monitored by nucleolar and ribosomal stress responses which induce apoptosis and/or cell cycle arrest. Therefore, I …

Development Of Cellular High Throughput Assays To Determine The Electrophysiological Profile Of Gaba(A) Receptor Modulators For Neurology And Immunology, Nina Yina Yuan

Theses and Dissertations

Gamma (γ) -aminobutyric acid (GABA) is the major inhibitory neurotransmitter found in

the mammalian central nervous system. Its effect stems from its ability to cause the opening of ion channels which causes an influx of negatively charged chloride ions or an efflux of positively charged potassium ions. This hyperpolarization of the neuron lowers the threshold for neuronal firing. This has an overall inhibitory effect on neurotransmission, decreasing the excitability of the neuron and diminishing the likelihood of a successful action potential occurring. There are two classes of GABA receptor: ligand-gated GABAA receptor (GABAAR) and metabotropic GABAB receptor (GABABR). The GABAAR …

Improving The Roadside Environment Through Integrating Air Quality And Traffic-Related Data, Christine M. Kendrick

Dissertations and Theses

Urban arterial corridors are landscapes that give rise to short and long-term exposures to transportation-related pollution. With high traffic volumes, congestion, and a wide mix of road users and land uses at the road edge, urban arterial environments are important targets for improved exposure assessment to traffic-related pollution. Applying transportation management strategies to reduce emissions along arterial corridors could be enhanced if the ability to quantify and evaluate such actions was improved. However, arterial roadsides are under-sampled in terms of air pollution measurements in the United States and using observational data to assess such effects has many challenges such as …

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …