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Investigation Of Behavioral And Cellular Changes In The Maternal Immune Activation Model Of Autism Spectrum Disorders, Shreya Roy

Theses & Dissertations

Maternal infection during pregnancy, which leads to maternal immune activation (MIA), is an environmental risk factor for autism spectrum disorders (ASD). MIA can be induced in mice and their offspring exhibit behaviors that model the core symptoms of ASD. One of the core behavioral symptoms in ASD patients is presence of increased repetitive behavior, which is modeled by an increase in marble burying in MIA mice. It has been shown that the deficits seen in MIA mice are associated with the dysregulation of cytokine levels in the developing brain, specifically an increase in pro-inflammatory cytokines. In this thesis, I tested …

Impact Of Estrogen Receptor Alpha On Sle1-Induced Loss Of Tolerance, Shayla D. Yoachim

Theses & Dissertations

The autoimmune disease lupus shows a significant female sex bias. This sex bias may be due to the ability of estrogens to promote loss of tolerance to chromatin, the initial loss of tolerance event in lupus. Previously, we demonstrated that the ability of estrogens to promote lupus in (NZBxNZW) F1 mice is dependent on signaling via estrogen receptor alpha (ERα). The Sle1 lupus susceptibility allele controls loss of tolerance to chromatin, and C57BL/6 (B6) mice carrying the Sle1 lose tolerance and develop anti-chromatin autoantibodies and spontaneously activated immune cells. Loss of tolerance occurs earlier and with a higher penetrance in …

Prevention Of Experimental Periodontitis In Rats With A Simvastatin Prodrug, Aaron Bradley

Theses & Dissertations

Introduction: Simvastatin (SIM) is a hypolipidemic drug that has been shown to have anti-inflammatory and bone anabolic properties. The aim of this study was to examine the effects of novel locally-applied SIM conjugated with methoxypolyethylene glycol to form micelles (SIM/SIM-mPEG) in an experimental periodontitis model in rats using micro-computed tomography (µ-CT) and histologic evaluation.

Methods: Experimental periodontitis was induced using silk ligatures around the maxillary right second molar (M2) in 40 Sprague-Dawley rats. Rats were divided into five groups using SIM/SIM-mPEG at 0.5, 1.0, or 1.5 mg SIM doses, mPEG-alone or no drug (ligature-alone) injected into the palatal M1-M2 gingiva …

Characterization Of The Replication Of Coxsackievirus B3 With A Mutationally Disrupted Cre(2c) And The Use Of Creatinine-Hydrochloride As An Antibacterial Agent, Shane E. Smithee

Theses & Dissertations

Following natural or experimental infection, and in cell culture, coxsackie B virus (CVB) RNA can persist for weeks in the absence of CPE yet with detectable viral RNA. Earlier studies in our laboratory demonstrated that this persistence produced viral RNA with up to 49 nucleotide deletions at the 5’ genomic terminus, partially degrading the cloverleaf (or domain I), an RNA structure that is required for efficient viral replication. A cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] templates the addition of two uridine residues to the virus-encoded RNA replication primer, VPg, prior to genomic replication. Because …

The Impact Of Gasoline Prices On Medical Care And Costs Of Motor Vehicle Injuries, He Zhu

Theses & Dissertations

Background Traffic safety has placed a tremendous economic and social burden on individuals and nations. Gasoline prices have been linked to traffic safety in the recent studies. Higher gasoline price may prompt people to reduce expenses by changing travel distance and frequency, transportation mode, or driving behaviors.

Objective This study aims to examine the relationship of gasoline prices to hospital utilization and cost for motorcycle and non-motorcycle motor vehicle injuries in the United States.

Methods Data on inpatient hospitalization for motor vehicle injuries were obtained from the 2001-2010 Nationwide Inpatient Sample, which is part of the Healthcare Costs and Utilization …

A Comparison Of Measurement Systems To Score Sleep Disturbance For Children With Autism Spectrum Disorders, Aaron Lesser

Theses & Dissertations

Direct observation of children’s sleep disturbance in the home is critical to understanding child behavior while awake and determining qualitative features of the sleep environment, but obtaining these data from an in-home recorded video, second-by-second, is impractical in terms of scoring time because observers score when the child is asleep and awake. In Studies 1 and 2, we conducted an analog study to assess a motion-detection camera to determine whether it would be suitable to measure children’s sleep disturbance. In Study 3, we obtained in-home measures of sleep disturbance for three children with an autism spectrum disorder using a motion-detection, …

Myeloid-Derived Suppressor Cells Contribute To The Subversion Of Innate Immunity During Staphylococcus Aureus Biofilm Infection, Cortney E. Heim

Theses & Dissertations

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes that are potent inhibitors of T cell activation. A role for MDSCs in bacterial infections has only recently emerged, and our laboratory was the first to demonstrate a functional role for MDSCs during Staphylococcus aureus (S. aureus) biofilm infection. Biofilm infections often lead to significant morbidity due to their recalcitrance to antibiotics and ability to subvert immune-mediated clearance by skewing the immune response toward an anti-inflammatory, pro-fibrotic phenotype. Therefore, we examined whether MDSCs could play a role in this process. CD11b⁺Gr-1⁺ MDSCs …

Characterization And Target Identification Of Non-Toxic Ikkβ Inhibitors For Anticancer Therapy, Elizabeth Blowers

Theses & Dissertations

IKKβ is a key kinase in the canonical NF-κB pathway. Transient activation of IKKβ is required for normal immune response while sustained activation has been implicated in cancer. To date, no IKKβ inhibitor has been approved for clinical use as a chemotherapeutic, likely due to unexpected toxicities associated with blocking the transient activation of IKKβ. We hypothesized that an IKKβ inhibitor that allows transient activation of IKKβ, but not sustained activation of IKKβ, could inhibit cancer growth without inducing toxicity.

As such, we identified a small molecule inhibitor, 13-197, that allows the transient activation of IKKβ but not the sustained …

Development Of Hypoxia Trapping Enhanced Bb2r-Targeted Radiopharmaceutics For Prostate Cancer, Zhengyuan Zhou

Theses & Dissertations

The Gastrin-Releasing Peptide Receptor (BB2r) has been investigated as a diagnostic and therapeutic target for prostate and other cancers due to the high expression level on neoplastic relative to normal tissues. A variety of BB2r-targeted agents have been developed utilizing the bombesin(BBN) peptide, which has shown nanomolar binding affinity to human BB2r. However, as with most of the low-molecular weight, receptor-targeted drugs, a major challenge to clinical translation of BB2r-targeted agents is the low retention at the tumor site due to intrinsically high diffusion and efflux rates. Our laboratory seeks to address this deficiency by developing synthetic approaches to selectively …

Occupational Exposure To Isoflurane Anesthetic Gas In The Research Environment, Andrea R. Mulvenon

Theses & Dissertations

This dissertation is a compilation of studies related to the halogenated anesthetic gas isoflurane. Historically, halogenated anesthetic gases have been used in the health care industry. In 1977 the National Institute for Occupational Safety and Health (NIOSH) issued a recommended exposure limit (REL) of two parts per million (ppm) averaged over one hour of exposure for halogenated anesthetic gases (NIOSH 1977). The purpose of the standard was to protect healthcare workers from exposure to halothane, methoxyflurane, and chloroform. However, isoflurane only became available after the NIOSH REL was adopted. Therefore, the NIOSH REL is not directly applicable to isoflurane. Moreover, …

Role Of Redox-Sensitive Calcium/Calmodulin-Dependent Protein Kinase Lla In Angiotensin Ii Intra-Neuronal Signaling And Angiotensin Ll-Mediated Hypertension, Urmi Basu

Theses & Dissertations

Activation of renin-angiotensin system and elevated levels of circulating and brain angiotensin II (AngII) has been implicated in the pathogenesis of neuro-cardiovascular diseases, such as hypertension and heart failure. In central neurons AngII increases generation of reactive oxygen species (ROS), which in turn regulates neuronal ion channels. Previous studies have demonstrated that ion channels can also be regulated by protein kinases, such as calcium /calmodulin-dependent protein kinase II (CaMKII) as a downstream mediator of AngII signaling. In the heart, CaMKIIδ undergoes oxidation upon AngII stimulation and increased pro-oxidant conditions. However, the exact mechanism by which AngII and ROS regulate CaMKIIα, …

Risk Factors For Agricultural Injury: An Evaluation Using Systematic Review And Injury Surveillance, Rohan Mahadeo Jadhav

Theses & Dissertations

Purpose- Agriculture is the most hazardous industry in the United States. The effectiveness of intervention programs for injury prevention can be improved by acquiring knowledge of risk factors for occupational injury in agricultural operators. The landscape of agriculture is changing in the U.S. Agricultural populations, environments and risk factors are changing as well with the changes in the structure of farms and ranches. The objective of this study was to identify significant risk factors for agricultural injury based on the literature and three years of injury surveillance data covering seven U.S. states. Methods- We conducted a systematic review of reported …

Roles Of Serum Lycopene In The Prevalence And Mortality Of Metabolic Syndrome In The Adult Population, Guang-Ming Han

Theses & Dissertations

Metabolic syndrome (MetS) is a cluster of metabolic disorders, including increased fasting glucose, blood pressure, plasma triglyceride, reduced high-density lipoprotein cholesterol and abdominal obesity. It leads to an increased risk of cardiovascular disease and diabetes. The growing prevalence of MetS is strongly related to the increasing prevalence of overweight/obesity. As an antioxidant, lycopene can reduce the risk of MetS. However, it is unclear whether lycopene has similar effects among overweight/obese individuals and whether lycopene can reduce the risk of mortality among individuals with MetS. The purpose of this study was to explore the roles of lycopene in the prevalence and …

Protein Therapy For The Treatment Of Vascular Calcification In Patients With End-Stage Renal Disease, Janice L. Cunningham

Theses and Dissertations

Premature death from cardiovascular disease is especially high in patients with chronic kidney disease (CKD). Vascular calcification is a potent risk factor for developing cardiac-related morbidity and mortality and is especially prominent within the CKD population. Deficiencies in serum levels of fetuin-A as well as inadequate production of matrix Gla protein (MGP) correlate inversely with the extent of vascular calcification and time spent on dialysis. Fetuin-A is a well-known systematic regulator of bone metabolism and MGP is a local antagonist of bone forming proteins. To meet the clinical need of at-risk patients prone to cardiac-related mortality. We propose a targeted …

Role Of Hippo-Yap Signaling In Mitosis And Prostate Cancer, Lin Zhang

Theses & Dissertations

The Hippo pathway controls organ size and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. KIBRA [kidney and brain expressed protein] is an upstream regulator of the Hippo-YAP signaling. The role KIBRA plays in mitosis has not been established. We show that KIBRA activates the Aurora kinases during mitosis and KIBRA promotes the phosphorylation of large tumor suppressor 2 by activating Aurora-A. We further show that knockdown of KIBRA causes mitotic abnormalities, including defects of spindle and centrosome formation and chromosome misalignment. The transcriptional co-activator with PDZ-binding motif is a downstream effector of the Hippo tumor suppressor pathway. In the …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

A Functional Genomics Analysis Of Glycine Max Vesicle Membrane Fusion Genes In Relation To Infection By Heterodera Glycine, Keshav Sharma

Theses and Dissertations

Soybean cyst nematode (SCN), a major pathogen of soybean worldwide, causes huge losses in soybean production. Various approaches including cloning of genes to combat this devastating disease help to better understand the cellular function and immune responses of plants. Membrane fusion genes are the important regulatory parts of vesicular transport system, which works through packaging of intracellular compounds and delivering them to apoplast or nematode feeding sites to induce an incompatible reaction. The incompatible nature of membrane fusion proteins such as SNAP25, Munc18, Syntaxin, Synaptobrevin, NSF, Synaptotagmin and alpha-SNAP are conserved in eukaryotes and regulate the intracellular function to combat …

Allelopathy In The Non-Native Macrophyte, Myriophyllum Spicatum And Its Influence On Trophic Dynamics In Aquatic Systems, Daniel J. Sullivan

Theses and Dissertations

Non-native macrophytes structurally impact aquatic assemblages, yet little is known regarding how they influence energy pathways in freshwater ecosystems. Allelopathy in Eurasian watermilfoil- Myriophyllum spicatum has been shown to target basal epiphytic organisms resulting in differences in assemblage structure of colonizing epiphyton between M. spicatum and native M. sibiricum. I conducted a growth chamber experiment to investigate the hypothesis that differences in assemblage structure of colonizing epiphyton between these two macrophytes influence trophic dynamics within aquatic systems. My data suggest M. spicatum produces higher concentrations of allelochemicals, resulting in a more diverse epiphytic assemblage compared to M. sibiricum. This could …

Characterization Of Lipoxygenase (Lox) Gene Family And Snp Validation In Relation To Aflatoxin Resistance In Maize (Zea Mays L.), Oluwaseun Felix Ogunola

Theses and Dissertations

An efficient approach to combat the accumulation of aflatoxin is the development of germplasm resistant to infection and spread of A. flavus in maize, one of the most important cereal grains in the world. Lipoxygenases (LOXs) are a group enzymes that catalyze oxygenation of polyunsaturated fatty acids (PUFAs). LOX derived oxilipins play critical roles in plant defense against pathogens such as A. flavus. The objectives of this study were to report sequence diversity and expression patterns for all LOX genes, and map their effect on aflatoxin accumulation via linkage and association mapping. Genes GRMZM2G102760 (ZmLOX 5) and GRMZM2G104843 (ZmLOX 8) …

Effect Of Carbohydrate Supplement On Cardiovascular And Metabolic Responses To Dual Concurrent Stressors, Matthew John Mcallister

Theses and Dissertations

Chronic psychological and physiological stress is linked to a high prevalence of cardiovascular disease (CVD). Potentially dangerous cardiovascular responses (e.g., exacerbated cortisol production) can occur with high levels of stress and chronic hypercortisolemia is associated with CVD. The ingestion of carbohydrate (CHO) prior to physical stress may attenuate cortisol responses to stress. The purpose of this project was to investigate the potential effect of CHO ingestion on cortisol production and responses to concurrent stress challenges. Sixteen apparently healthy non-smoking men 21-30 years old participated in a randomized, cross-over, double blind, placebo controlled trial. Participants were tested on four separate sessions. …

Effect Of Omega-3 Fatty Acid Supplementation To Gestating And Lactating Mares On Milk Igg And Fatty Acid Composition, Mare And Foal Blood Concentrations Of Igg, Fatty Acid Composition, Insulin And Glucose, And Placental Efficiency, Lauren B. Hodge

Theses and Dissertations

There are conflicting results from previous research evaluating the effects of dietary omega-3 fatty acid supplementation on IgG concentration of colostrum, milk and foal blood. No research has been done on the effect of omega-3 fat supplementation on the placental efficiency of horses or the nitrite concentrations of the placenta as an indicator of vascularization. This study examined the effect of dietary omega-3 supplementation on composition of milk, mare and foal serum and if it will result in transfer of fatty acid in utero as well as providing the foal with adequate IgG concentrations in the milk and colostrum. Omega-3 …

Evolutionary And Ecological Causes And Consequences Of Trophic Niche Variation In Ursids, Diana Jean Raper Lafferty

Theses and Dissertations

Individual variation and fitness are the cornerstones of evolution by natural selection. The trophic niche represents an important source of phenotypic variation on which natural selection can act. Although individual variation is fundamental to species-level ecological and evolutionary change, individual variation is often ignored in population-level approaches to wildlife ecology, conservation and management. Failing to link individual resource use to fitness or to biological outcomes related to fitness limits us to managing for the average resource needs of a population, which may be insufficient for protecting the diversity of resource use within populations and the underlying eco-evolutionary processes that generate …

Factors Influencing Malawian Tobacco Farmers' Decisions Regarding Contracting, Penjani Singini

Theses and Dissertations

Tobacco plays a very significant role in Malawi’s economy by being the largest foreign exchange earner for the economy. The Integrated Production System was implemented in 2012 to promote contract production and also improve quality of tobacco which would therefore fetch higher prices for farmers. Contract farming has been believed to be potentially beneficial, but many farmers still choose not to produce under contract. This study examines factors that influence farmers’ tobacco contracting decisions. 300 farmers were interviewed for the study using a structured questionnaire. Data was analyzed with logit model using SAS software. Expected auction market price, expected fertilizer …

Human Carbonic Anhydrase Ii; Preparation, Metal-Substitution, Activity, And Inhibition, David L. Wilson

Theses and Dissertations

This report details the activities and inhibition of metal-substituted human carbonic anhydrase II (M-HCA-II). The traditional activities (hydrolysis of CO2 and para-nitrophenol acetate) in addition to new activities (oxidation of 2-aminophenol, disproportionation of H2O2, and disproportionation of superoxide) were investigated. Values reported for the relative hydrolytic activities of M-HCA-IIs are reported here for the first time, ranging from 47.5 % (plus or minus 0.6) to 86 % (plus or minus 4) for the hydrolysis of CO2 and from 0.299 % (plus or minus 0.012) to 4.72 % (plus or minus 0.015) for the hydrolysis of para-nitrophenol acetate. With respect to …

Comparative Evaluation Of Three Different Methodologies For Determining Embryo Temperature In Broiler Hatching Eggs During Incubation, Opeyemi Christiana Olojede

Theses and Dissertations

Temperature is the most important among several factors that are needed for optimum avian embryonic development during incubation. Previous studies have implied that incubation temperature may have an impact on chick quality and post hatch performance. The use and accuracy of different methodologies for the estimation of embryonic temperature and eggshell conductance values during incubation were determined in three trials. Results suggested that air cell temperature using transponders may be used for the estimation of embryo temperature from 12 through 19 days of incubation and the subsequent calculation of eggshell conductance and specific eggshell conductance values. A final trial was …

Lgr5 Activates Tgfβ Signaling And Suppresses Metastasis In Colon Cancer, Xiaolin Zhou

Theses & Dissertations

Metastasis is the major cause of death in colorectal cancer patients, mainly due to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of colorectal cancer metastasis is, therefore, essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies to prevent or target metastasis. LGR5 is leucine-rich repeat containing G protein-coupled receptor (GPCR) and was discovered as a marker for proliferating adult stem cells in the small intestine. LGR5 and its homologs LGR4 and LGR6 are receptors of R-spondins (RSPOs), which are secreted agonists of canonical …

The Effect Of Oxygen On Bile Resistance In Listeria Monocytogenes, Morgan Layne Wright

Theses and Dissertations

Listeria monocytogenes is a Gram-positive facultative anaerobe that is the causative agent of the disease listeriosis and is responsible for nearly 20% of all food-related deaths in the United States. The ability of this bacterium to cause infections is proposed to correlate to its ability to resist the bactericidal properties of bile acids found in bile. Bile resistance mechanisms have exhibited increased activity under anaerobic conditions. Therefore, we hypothesized that limited oxygen could enhance the bile resistance of L. monocytogenes. Upon survival analysis, viability for virulent strains F2365, EGD-e, and 10403S increased upon 10% porcine bile extract under anaerobic conditions. …

The Effect Of Therapeutic Riding On Classroom Attention Of Children With Developmental Disabilities, Morgan Jessica Patterson

Theses and Dissertations

Research indicates children with disabilities benefit from therapeutic horseback riding (TR). This study examined the impact TR had on attention behaviors of five children with various developmental disabilities in a preschool classroom. Children were observed in the classroom setting twice weekly for 10 weeks on a day they participated in TR services and on a day they did not participate in TR. Single case experiments suggested there was not a significant difference in all but one child’s sustained attention in the classroom on days children received TR services. An independent samples t-test suggested there was no significant difference in scores …

The Gastrointestinal Tract Microbiota Of The Obligate Bamboo Foragers, The Giant Panda (Ailuropoda Melanoleuca) And The Red Panda (Ailurus Fulgens), Candace Lareine Williams

Theses and Dissertations

Previously, the exact phylogenetic relationship between the giant panda (Ailuropoda melanoleuca) and the red panda (Ailurus fulgens) has been unclear, but with the advent of molecular sequencing technologies, these two animals are now known to be distantly related. Although taxonomically distinct, these two panda species have several things in common, primarily their almost exclusively bamboo diet, but also their similar physical adaptations to their diet and their sympatry in some locations. What was unknown was if their similarities also extended to their gastrointestinal tract (GIT) microbiota. Using next-generation 16S rRNA parallel sequencing technologies, we uncovered several factors that impact bacterial …

Ecology Of Yellow Rail (Coturnicops Noveboracensis) Overwintering In Coastal Pine Savannas Of The Northern Gulf Of Mexico, Kelly Marie Morris

Theses and Dissertations

The Yellow Rail (Coturnicops noveboracensis) is a migratory nongame bird of high conservation priority throughout its entire range. The objectives of this study were: (1) assess Yellow Rail occupancy in the context of prescribed fire regime in pine savanna habitats of Mississippi and Alabama and (2) assess Yellow Rail habitat use in pine savanna habitats of coastal Mississippi. Yellow Rail occupancy decreased significantly with time since fire and increased with grassland patch size. Throughout the study area Yellow Rail maintained small (mean = 3.37 ha) home ranges aggregated within study areas, indicating suitable habitat may be limited. Yellow Rail used …