Life Sciences Commons^™

Structural Insights Into Dna Replication And Lesion Bypass By Y Family Dna Polymerases, Kevin N. Kirouac

Electronic Thesis and Dissertation Repository

Y family DNA polymerases are specialized enzymes for replication through sites of DNA damage in the genome. Although the DNA damage bypass activity of these enzymes is important for genome maintenance and integrity, it is also responsible for DNA mutagenesis due to the error-prone nature of the Y family. Understanding how these enzymes select incoming nucleotides during DNA replication will give insight into their role in cancer formation, aging, and evolution. This work attempts to mechanistically explain, primarily through X-ray crystallography and enzymatic activity assays, how Y family polymerases select incoming nucleotides in various DNA replication contexts. Initially, we sought …

When Curiosity Kills More Than The Cat: The Perils Of Unchecked Scientific Inquiry, Jamie Shannon

Pomona Senior Theses

This work analyzes the ecological, physical, emotional and health impacts of the US nuclear testing done in the Marshall Islands in the mid-20th century.

Sublethal Toxicity Of Microcystis And Microcystin-Lr In Fish, Emily Dawn Rogers

Doctoral Dissertations

The occurrence of blooms of toxic cyanobacteria in freshwater environments is a global ecological and public health concern. Species of Microcystis are of particular importance because blooms occur in many freshwater environments throughout the world and microcystin toxin concentrations can exceed World Health Organization advisory levels. While microcystin has been associated with fish kills, sublethal effects of chronic exposure at environmentally relevant concentrations are relatively unknown. The objective of this research was to evaluate toxicity of microcystin and Microcystis in fish during all life history stages. We evaluated global gene expression response in larval zebrafish (Danio rerio), and …

Pharmacokinetic Evaluation Of The Blood: Tissue Relationship In Poultry: Screening For Antibiotic Residues In Chicken Muscle, Ixchel Reyes Herrera

Graduate Theses and Dissertations

During their life, humans are exposed to numerous substances that are naturally present in the environment or that are the result of man made processes, including heavy metals, persistent organic pollutants, pesticides and veterinary drugs. Some of these substances can leave residues in food products and possibly expose consumers to their potential toxic effects. To address these problems extensive regulatory efforts are devoted to prevent, detect and control these substances from reaching the food supply. However, given the vast diversity of food products that requires monitoring and the immense diversity of potential chemical contaminants, the need for an efficient and …

Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff

Chancellor’s Honors Program Projects

No abstract provided.

Pharmacokinetics And Therapeutic Uses Of Mesna, Murray J. Cutler

Electronic Thesis and Dissertation Repository

In the early 1980s, significant advancement in the safety of ifosfamide therapy was achieved by co-administrating mesna (sodium 2-mercaptoethane sulfonate) to prevent dose-limiting hemorrhagic cystitis. Mesna exerts its protective effect within the urine, where its free sulfhydryl group is able to conjugate cytotoxic metabolites. Within the circulation, however, mesna exists primarily as its inactive disulfide, dimesna. Dimesna is currently undergoing clinical development as a prodrug (BNP7787) to treat cisplatin-induced nephrotoxicity. Remarkably, chemoprotection is achieved without attenuation of efficacy of co-administered anti-cancer agents. This is widely attributed to the kidney-specific disposition and stability of dimesna.

We sought to evaluate the role …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Trace Metal Concentrations Across Trophic Levels In Cotton Fields Of Xinjiang Province, China, Jessica Quinn

All Student Theses

Trace metals become concentrated in urban and peri-urban soils with the use of agricultural practices and industrial emissions. Fertilizers, liming, sewage sludge, and irrigation water contain metals which accumulate in agricultural fields and pose a risk to humans and wildlife. Coal plants and brickyards release metals into the atmosphere which are deposited on soil and plant surfaces. This research quantifies the concentrations of nine trace metals in three different soil types. A total of 116 rodents were sampled in cotton fields and a desert. Cotton plants and triplicate soil samples were collected with each rodent capture. Soil samples were analyzed …

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

Dissertations & Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response …

A Comparative Study Of Three Growing Media And Four Plant Groups Under Extensive Green Roof Conditions In San Luis Obispo, Ca, Todd Alan Nelson

Master's Theses

ABSTRACT A Comparative Study of Three Growing Media and Four Plant Groups Under Extensive Green Roof Conditions in San Luis Obispo, California Todd A. Nelson Green roof growing media and plant species are critical factors when deciding on the best materials for a project. Growing media must be chosen in accordance with load bearing capacities of structures and water requirements of the plant material. Plant species must be able to thrive in the climate of the green roof and withstand a green roof’s harsh environment. The objectives of this research were: (1) to determine which of three extensive green roof …

Analysis Of Anthropogenic Effects On Topsoil Throughout The California Polytechnic State University Campus In San Luis Obispo, Brooke L. Hamilton

Earth and Soil Sciences

Soils reflect the health of a landscape, and in many cases carry the burden of anthropogenic activity, continually changing in characteristics such as pH, soil texture, soil structure, carbon:nitrogen ratios (C:N), and chemical composition. In a study sampling six different soils on the California Polytechnic State University campus in San Luis Obispo, these five soil characteristics were tested for and the results were determined. Soil samples consist of the top 5-10 cm of soil profiles, with sample sites varying according to degree of human contact; the locations the samples were taken from are as follows: (1) Walters Creek Ranch pasture, …

Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou

Animal Science

Poisonous Rangeland Plants in San Luis Obispo County is a comprehensive educational guide to rangeland plants that are toxic to domestic livestock. This guide begins with an exploration of how the biological systems are affected by the poisonous plant toxins. The biochemistry behind these toxins is included in the discussion. Next, reference material for fourteen plants that inhabit San Luis Obispo County is provided. This information includes specific toxins found in poisonous plants, affected animals, symptoms of poisoning, stages of growth, lethal dose, and distribution of the plant in California. This section of the guide is filled with helpful photos …

Hypoxia And Fetal Programming Of Cardiovascular Dysfunction, Qin Xue

Loma Linda University Electronic Theses, Dissertations & Projects

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Of all the stresses to which the fetus is subjected, perhaps the most important and clinically relevant is that of hypoxia. The goal of this project is to test the hypothesis that chronic hypoxia during gestation adversely affects fetal cardiovascular development and impairs cardiac function in offspring. In the first part of project, we tested the hypothesis that chronic hypoxia adversely regulates contractility of fetal pulmonary arteries and veins in sheep residing at high altitude (3,801 …

Quantifying Legacy Effects Of Managed Disturbance On Sagebrush Steppe Resilience And Diversity, Julie Ripplinger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Land-use legacies can affect landscapes for decades to millennia. A long history of shrub management exists in the sagebrush steppe of the Intermountain West where shrub-removal treatments, a type of managed disturbance, have been implemented for over 50 years to reduce sagebrush cover. The assumption behind managed disturbances is that they will increase forage for domestic livestock and improve wildlife habitat. However, the long-term effects of managed disturbance on plant community composition and diversity are not well understood. We investigated the legacy effects of three common types of managed disturbance (chemical, fire, and mechanical treatments) on plant community diversity and …

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

Dissertations & Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through …

Adaptivearc And The Future Of The Energy Industry, Trevor Chase

Earth and Soil Sciences

No abstract provided.

A Gis Analysis Of The Environmental Variables Related To Rift Valley Fever Outbreaks, Jacqueline Florette Jackson

Health Services Research Dissertations

Rift Valley fever is a mosquito-borne disease that causes widespread febrile illness and mortality in domestic animals as well as humans (Gaff, 2007). Rift Valley fever virus was first isolated in 1931 (Daubney, 1931), and since then, outbreaks have occurred in sub-Saharan Africa, southern Africa, Egypt, Saudi Arabia, Yemen and Madagascar, proving it to be a virus able to invade ecologically diverse regions (Gaff, 2007). The potential introduction of Rift Valley fever into the United States suggests the potential for human infection and major economic disruption. It is important to understand the role environmental variables have played in historical outbreaks …

Particulate Characterization And Control Evaluation For Carbon Fiber Composite Aircraft Crash Recovery Operations, Matthew R. Ferreri

Theses and Dissertations

Within the United States Air Force (USAF) Advanced Composite Material (ACM) is gaining an increasing use in military aircraft. With the number of aircraft that have increasingly large amounts of ACM materials, the probability of an incident with one of these aircraft also increases. When such an incident occurs the aircraft needs to be disassembled, removed, and later inspected as part of the accident investigation process. This disassembly process is termed “Crash Recovery Operations.” Carbon fibers have been shown to be hazardous to human health and a pilot study raised the suspicion that nanosized aerosol may be generated during the …

Low Dose Sarin Leads To Murine Cardiac Dysfunction, Michael W. Horenziak

Theses and Dissertations

It has been reported that low dose sarin is associated with long-term pathology in the brain and heart; however, the effects of sarin on the heart have yet to be determined. In addition, sarin has been implicated as an etiological agent in Gulf War Illness. Thus, the role of sarin in producing illness has important military consequences. This study used echocardiography, electrocardiography, and histology to determine sarin’s effect on the murine cardiovascular system. C57BL/6J mice were injected with sarin at 0.4 LD50, 0.5 LD50, or saline on two consecutive days and studied for 10 weeks post exposure. The sarin animals …

Gabab Regulation Of Methamphetamine-Induced Associative Learning, Robin Michelle Voigt

Dissertations

Addiction is a chronic, relapsing disorder for which strikingly few effective therapies exist, and there are no FDA-approved pharmacotherapies for methamphetamine (Meth) addition. There is an immense need to identify the neurobiological underpinnings of psychostimulant addiction and develop efficacious drug therapies to compliment the current mainstay treatment of behavioral/cognitive therapy.

Re-exposure to cues associated with psychostimulants (e.g., drug paraphernalia) increase neuronal activity and can elicit drug-craving and -seeking; an effect which is profound and long-lasting. A mechanism to disrupt those brain processes which are necessary to maintain the association may reduce the incidence of cue-elicited relapse.

Conditioned place preference (CPP) …

A Role For Lipid Rafts In Egfr Tki Resistance In Breast Cancer, Mary Elizabeth Irwin

Wayne State University Dissertations

Breast cancer can be divided into genetic sub-types including luminal, HER2+, and basal-type. With the introduction of targeted therapies against estrogen receptor and HER2 receptor mortality rates of American women with breast cancer have declined. Unfortunately, basal-type breast cancers, which have the worst clinical outcome, do not express estrogen receptor or HER2, and as such, have no targeted therapeutic option. The epidermal growth factor receptor is an attractive target for therapeutics in basal-type breast cancer, as it is over-expressed in 60% of these cases. Also, over-expression of EGFR correlates with poor patient prognosis. Unfortunately, inhibitors of EGFR have shown little …

Spectroscopic Study Of The Inhibition Of Calcium Oxalate Calculi By Larrea Tridentata, Luis Alonso Pinales

Open Access Theses & Dissertations

The causes of urolithiasis include such influences as diet, metabolic disorders, and genetic factors which have been documented as sources that aggravate urinary calculi depositions and aggregations, and, implicitly, as causes of urolithiasis. This study endeavors to detail the scientific mechanisms involved in calcium oxalate calculi formation, and, more importantly, their inhibition under growth conditions imposed by the traditional medicinal approach using the herbal extract, Larrea tridentata. The calculi were synthesized without and with Larrea tridentata infusion by employing the single diffusion gel technique. A visible decrease in calcium oxalate crystal growth with increasing amounts of Larrea tridentata herbal infusion …

Weight Gain Among Adults With Intellectual Disabilities Receiving Atypical Antipsychotics, Sherri Lyn Transier

Doctoral Dissertations

The present study assessed whether the atypical antipsychotic agents olanzapine, risperidone, and quetiapine are associated with significant weight gain among adults with intellectual disabilities after 6 months of drug treatment. The body weights of 79 participants were retrieved 6 months prior to the initiation of drug treatment, at the start of the atypical antipsychotic agent, and after 6 months of drug therapy. Each individual served as his or her own control by utilizing pretreatment baseline trends in weight change to calculate a dependent measure of adjusted posttreatment weight gain. Doing so allowed for a stringent determination of the liability for …

Polychlorinated Biphenyl-Induced Endothelial Cell Dysfunction And Its Modulation By Dietary Lipids, Zuzana Majkova

University of Kentucky Doctoral Dissertations

Cardiovascular diseases are the number one cause of death in Western societies. Endothelial dysfunction is an early event in the pathology of atherosclerosis, which is an underlying cause in the majority of cardiovascular events. Exposure to persistent environmental pollutants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of atherosclerosis.

First, we tested a hypothesis that coplanar PCBs, dioxin-like chemicals with affinity for aryl hydrocarbon receptor (AhR), can stimulate up-regulation of monocyte chemoattractant protein-1 (MCP-1), an endothelium-derived chemokine that attracts monocytes into sub-endothelial space in early stages of atherosclerosis. Coplanar PCBs 77 and 126 increased expression of …

Toxicodynamics And Biotransformation Of Azaspiracids Incorporating Liquid Chromatography-Tandem-Mass Spectrometry (Lc-Ms/Ms) Techniques., Daniel O'Driscoll

Theses

Azaspiracids (AZAs) are a family of lipophilic polyether marine biotoxins, that have caused a number of human intoxication incidents in Europe since 1995, which was the first incident reported following the consumption by consumers of intoxicated shellfish {Mytilus edulis). This class of phycotoxins has been responsible for extended closures of shellfisheries in various locations around Europe, where levels of AZAl-3 are regulated in shellfish. Since their discovery in 1995, AZAs have become the focus of extensive research, resulting in the discovery of numerous analogues. Only AZAl and AZA2 have been found in phytoplankton and all the other analogues are believed …

Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang

Wayne State University Dissertations

Arsenic is a metalloid toxicant that is widely distributed throughout the earth's crust and causes a variety of health and environment problems. As an adaptation to arsenic-contaminated environments, organisms have developed resistance systems. In bacteria and archaea various ars operons encode ArsAB ATPases that pump the trivalent metalloids As(III) or Sb(III) out of cells. In these operons, an arsD gene is almost always adjacent to the arsA gene, suggesting a related function. ArsA is the catalytic subunit of the pump that hydrolyzes ATP in the presence of arsenite or antimonite. ArsB is a membrane protein which containing arsenite-conducting pathway. ArsA …

Retrieval Of Atmospheric Elemental Carbon Records Using Lake Sediments : Implications In Radiative Forcing, Tanveer Ahmed

Legacy Theses & Dissertations (2009 - 2024)

Elemental or black carbon (EC or BC) aerosols produced during incomplete combustion strongly absorb solar radiation and contribute to global warming, and cause cardiopulmonary disease. Long-term atmospheric EC measurements, [EC]_atm, are needed to validate global climate models to estimate the impact of EC on earth's temperature. Such data is sparse.

Arsenic Speciation Analysis Of Biological Fluids : A Study Of Liquid Chromatography Coupled To Analytical Atomic Spectrometric Instrumentation, Kanna Ito

Legacy Theses & Dissertations (2009 - 2024)

Arsenic exists as many different chemical forms including inorganic, methylated and dietary species. The toxicity of these species varies: some are highly toxic and can cause adverse health effects in many parts of the body; others are considered relatively non-toxic. Monitoring arsenic exposure is usually accomplished by its direct measurement in biological fluids. Urine is the specimen of choice for assessing arsenic exposure, because of its short biological half-life in blood. There have been very few studies of arsenic species in blood, yet such research can provide valuable information on arsenic distribution and its metabolism in the body.

Preparation And Application Of Transgenic And Knockout Mouse Models For Studies On Cytochrome P450 Functions, Yuan Wei

Legacy Theses & Dissertations (2009 - 2024)

The overall objective of this dissertation is to study the in vivo function of microsomal cytochrome P450 monooxygenases (P450s), which metabolize numerous drugs, chemical carcinogens, environmental pollutants, as well as endogenous signaling molecules such as steroid hormones and eicosanoids. The major research tool of this study involves the development of transgenic and knockout mouse models. The specific aims are 1) to study the in vivo function of NADPH-cytochrome P450 reductase (CPR) and CPR-dependent enzymes using a mouse model with a reversible hypomorphic Cpr gene; 2) to study the in vivo function of CYP2A13 with a CYP2A13- transgenic model; and 3) …

2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis

Browse all Theses and Dissertations

2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent toxin which inhibits the antibody response of B cells. The 3'IgHRR which is involved in transcriptional regulation of the heavy-chain polypeptide of antibodies is inhibited by TCDD. The hs1,2 enhancer region, isolated from the 3'IgHRR, is also inhibited while the isolated hs4 is activated by TCDD. This project sought to determine if that dichotomy in effects results from interactions at enhancer-specific binding sites for AhR, thought to mediate transcriptional effects of TCDD, and NFκB, a transcription factor involved in B cell activation. Here, I report a difference in the effect of TCDD on transcriptional activity …