Medicine and Health Sciences Commons^™

Characterization Of High-Voltage-Activated Calcium Channels In Retinal Bipolar Cells, Qi Lu

Wayne State University Dissertations

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca²⁺ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and …

Impact Of Cryoablation On Tumor Immunity, Jesse Veenstra

Wayne State University Dissertations

Background and Objectives: Percutaneous cryoablation is a minimally invasive procedure for tumor debulking, which has the potential to initiate or amplify tumor immunity through the release of tumor-associated antigens and endogenous danger signals. However, enhanced immunity is rarely observed in treated patients, suggesting the need for mechanistic analysis. The goal is to determine how cryoablation affects tumor specific immunity and if the response can be improved through exogenous TLR9 stimulation.

Methodology: We evaluated anti-Her2/neu immunity following cryoablation in wt BALB/c and tolerant NeuT mice inoculated with neu or Her2 expressing mammary tumors TUBO and D2F2/E2 respectively. Mice were treated with …

Roles Of Neuregulin1 In Neuromuscular Junction Development, Jiajing Wang

Wayne State University Dissertations

Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between nerve terminals, target muscles, and peri-synaptic glial cells, and thus requires reciprocal signals derived from every cell type. Neuregulin1s (NRG1s) are a family of predominantly neuronal growth and differentiation factors that are important for many aspects of nervous system development. In this thesis, both the effects of NRG1 on NMJ development and reciprocal effects of neurotrophic factors on NRG1 expression were studied as a means to define the complex regulatory communication at the NMJ. Using the chicken embryo as a model, methods were developed to study the …

Characterization Of Antimicrobial-Resistant Staphylococcus Spp. In Food Animals And Retail Meat, Kanika Bhargava

Wayne State University Dissertations

Antimicrobial resistance in Staphylococcus spp. is a worldwide epidemic concern in hospital and community settings. Food animals and retail meat are important reservoirs of these pathogens that can pose potential threat to humans. In this dissertation, we aimed to investigate the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Coagulase-negative Staphylococci (MRCoNS) in food animals and retail meat to provide insight into the role of agricultural environment in transmitting bacteria of human clinical significance. Furthermore, the potential application of phytochemicals as antimicrobials and antimicrobial adjuvants to control MRSA infections was explored.

CoNS recovered from food animals were characterized by …

Expression And Regulation Of Map Kinase Phosphatases 1 And 2 In Breast Cancer Tamoxifen Sensitivity, Kelly Haagenson

Wayne State University Dissertations

ABSTRACT

EXPRESSION AND REGULATION OF MAP KINASE PHOSPHATASES 1 and 2 IN BREAST CANCER TAMOXIFEN SENSITIVITY

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KELLY K. HAAGENSON

May 2013

Advisor: Dr. Malathy Shekhar

Co-Advisor: Dr. Gen Sheng Wu

Major: Cancer Biology

Degree: Doctor of Philosophy

The deregulation of cell signaling is a very important component in the development and progression of cancer. One group of signaling molecules that has been implicated in these processes is the Mitogen-Activated Protein Kinase (MAPK) family which consists of three major branches in mammalian cells: ERK, JNK and p38. The activity of these kinases has wide-ranging effects within the cell and must …

Fatty Acid Fate In Determining Oxidation And Inflammation In Adipose Tissue, Emilio Patrick Mottillo

Wayne State University Dissertations

Adipose tissue (AT) is a critical regulator of energy balance through its ability to store or oxidize free fatty acids (FFAs). White adipose tissue (WAT) functions as an anabolic organ to sequester and release FAs, in contrast brown adipose tissue (BAT) is a catabolic organ that oxidizes FAs. However, a comprehensive understanding of the role that FFAs play in the function of WAT and BAT is needed. Here we demonstrate that intracellular FAs enhance the expression of inflammatory cytokines by β3-AR activation in adipocytes, in which the expression of PAI-1 is partly mediated by the de novo synthesis of ceramides/sphingolipids. …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

The Effect Of Proalgazyme And Its Subfractions On Lipid Metabolism In Diet Induced Hypercholesterolemic Hamsters: Correlation With Plasma Metabolomic Profile, Andreea Geamanu

Wayne State University Dissertations

ABSTRACT

THE EFFECT OF PROALGAZYME AND ITS SUBFRACTIONS ON LIPID METABOLISM IN DIET INDUCED HYPERCHOLESTEROLEMIC HAMSTRES:

CORREALTION WITH PLASMA METABOLOMIC PROFILE

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ANDREEA GEAMANU

December 2013

Advisor: Dr. Smiti Gupta

Major: Nutrition and Food Science

Degree: Doctor of Philosophy

Background: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the preventative effect of an algae infusion, ProAlgaZyme (PAZ) and its subfractions (F1, F2, F3, F4) on plasma HDL in a hamster model. Further, the study aimed to identify the biologically active fraction of PAZ and to determine the …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

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MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …