Medicine and Health Sciences Commons^™

Astrocyte Sensitivity To Dopamine In Culture And Ex Vivo, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. This thesis illustrates effects of dopamine on cultured astrocytes and astrocytes in brain slices (ex vivo). In striatal cultures, extracellular dopamine triggered changes in astrocytic Ca²⁺ signaling and rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation, but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. To isolate possible mechanisms underlying these structural and functional changes, whole-genome RNA sequencing was …

Epigenetic And Purinergic Regulation Of Mast Cells Mediator Release, Zahraa Abdulmohsin Mohammed

Theses and Dissertations

Mast cells (MCs) are well known for their implications in allergic reactions. They are also known to have multiple functions in the innate and adaptive immune system. Their activation plays an essential role in many aspects of physiological and pathological conditions. Allergies are considered chronic conditions that affect more than 60 million people in the U.S. These diseases are driven by the activation of MCs in response to IgE-mediated antigen, rendering these cells as targets for the management of allergies and asthma. Therefore, this research considers the understanding of their activation and the regulation of their response to be an …

The Contribution Of Adipose Tissue From Ovariectomized Mice To Colon Cancer, Meredith Smith Carson

Theses and Dissertations

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when …

Effect Of Tcdd, An Environmental Contaminant, On Activation Of Ahr Leading To Induction Of Myeloid Derived Suppressor Cells (Mdscs) And The Ability Of Resveratrol, A Botanical, To Neutralize This Effect, Wurood Hantoosh Neamah

Theses and Dissertations

Aryl hydrocarbon receptor (AhR), is a ligand-activated transcription factor that integrates environmental, dietary, microbial and metabolic cues to control various cellular processes, such as the cell cycle, epithelial barrier function, cell migration and immune function. AhR was discovered as the receptor that binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leads to numerous of toxicological outcomes. In the current study, we discovered a critical role played by AhR, following activation by TCDD, in modulating a variety of immunological functions through regulation of epigenetic and microbial pathways. Our data demonstrated that AhR activation triggers MDSC mobilization from bone marrow to peritoneal …

Role Of Epigenetic, Molecular And Cellular Pathways In The Regulation Of Inflammation, William James Becker

Theses and Dissertations

Dysregulated inflammation is at the heart of countless human diseases. Graft rejection is the process by which an organ from an incompatible donor is rejected by the recipient whose immune cells attack the foreign tissue. Colitis is an inflammatory disorder caused by undue chronic inflammation in the colon and rectum that can progress to cancer. Colitis incidence is on the rise, especially in developing nations and Asia; and the list of patients who need organ transplants grow by the day. Therapies for both graft rejection and colitis are limited to immunosuppressive drugs that leaves patients vulnerable to infection, heart disease, …

Interdependent Mechanisms Of Stress Susceptibility, Julie Elaine Finnell

Theses and Dissertations

Social stress is a significant risk factor for the emergence of psychiatric disorders including depression and anxiety. While there are a number of commercially available therapeutic options for the treatment of these disorders, these treatments require weeks of continuous use to produce behavioral efficacy. It has also been suggested that these traditional therapies are only marginally effective in producing complete remission, suggesting that our understanding as it pertains to the mechanisms underlying stressinduced behavioral dysfunction is still in its infancy. In the last few years, inflammation has become a major focus in the field of stress and depression as clinical …

Three-Dimensional Plasma Cell Survival Microniche In Multiple Myeloma, Katrina A. Harmon

Theses and Dissertations

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled proliferation of long-lived plasma cells (PCs) in the bone marrow (BM), which constitute at least 10% of BM cellularity. Normally, long-lived plasma cells make up less than 1% of BM cells. Plasma cells become neoplastic when a clonal PC population produces a monoclonal immunoglobulin protein. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is made when there is an increase in monoclonal PCs within the BM, but less than 10%, and the patient does not present with end-organ damage, which is associated with active MM. Though not considered …

The Anti-Angiogenic Effects Of Sparstolonin B, Henry Rhodes Bateman

Theses and Dissertations

Sparstolonin B (SsnB) is a novel bioreactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. SsnB has demonstrated anti-inflammatory properties, inhibiting Toll-like receptor mediated inflammation in isolated macrophages and in mice. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including atherosclerosis, diabetic retinopathy, and tumor growth. The goal of the project was to investigate the anti-angiogenic effects of SsnB.

The first part of the project utilized in vitro functional assays to study how SsnB affected endothelial cells. SsnB inhibited endothelial cell tube …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Mass Spectrometry And Tandem Mass Spectrometry Characterization Of Protein Patterns, Protein Markers And Whole Proteomes For Pathogenic Bacteria, Jennifer Intelicato-Young

Theses and Dissertations

There have been many recent reviews published on MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight) MS (mass spectrometry) for identification of bacteria particularly with relevance to clinical microbiology. MALDI-TOF MS is now a mature technique for bacterial identification with great promise. The purpose of this review is to put into perspective MALDI-TOF MS and other widely used mass spectrometry methods for characterization of proteins. MALDI-TOF MS is used for rapid determination of a mass pattern of proteins for bacterial characterization; these proteins

are generally not identified. Alternatively, after gel separation, MALDI TOF-TOF MSMS (tandem mass spectrometry) or on-line LC-ESI MS-MS …

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

Resveratrol Attenuates The Development Of Trans-Aortic Constriction (Tac) Induced Heart Failure In Mice, Prakash Kumar Gupta

Theses and Dissertations

Heart failure (HF) still remains the leading cause of morbidity and mortality and imposes severe global affliction and enormous cost on the healthcare system. Although current pharmacological therapies have shown to slow down the progression of HF, but seems to have reached their limits in improving overall patient prognosis. Thus, an immediate call for novel alternate therapies are needed which act independently as well as in conjunction with current treatment modality. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload (PO) in mice. In the first series of studies, Male C57BL6 mice (26-28 g) …

High Fat Diet Induced Obesity In A Mouse Model For Colorectal Cancer, Kennerly Clinton Patrick

Theses and Dissertations

Obesity is widely correlated with the incidence of colorectal cancer (CRC). The exact mechanisms that link obesity to CRC risk have not yet been fully established, and only a limited number of animal models are available to study pathways involved in obesity-related colon carcinogenesis. The objective of this study was to determine the influence of HFD-induced obesity on AOM/DSS-mediated colorectal tumorigenesis, tumor proliferation, and symptom severity. Male C57BL/6 mice were fed a novel high fat diet, designed to mimic the standard American diet (12 % saturated fat & 28 % unsaturated fat), at 4 weeks of age until 16 weeks …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …