Physiology Commons^™

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

Assessment Of Presumed Sterility Of The Human Placenta And Maternal Bladder, Ali Alhousseini

Wayne State University Dissertations

Introduction

Preterm birth is the number one cause of neonatal morbidity and mortality. A causal link has been established between infection and preterm birth. Urinary tract infection is the number one infection in pregnancy. Evaluating the existence of a placental and maternal bladder microbiome is a major scientific and clinical milestone in perinatal medicine.

Methodology and Results

Chapter 2: This is a prospective case control study. 69 placentas were collected in a sterile fashion from six groups of women without infection: Term cesarean not in labor (n=18), term cesarean in labor (n=9), term vaginal (n=21), preterm cesarean not in labor …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

Estimating The Variables Of The Nonlinear Dynamical Theory Of Acute Cell Injury, Fika Tri Anggraini

Wayne State University Dissertations

This Dissertation is the first to estimate the variables D and S of the nonlinear theory of acute cell injury in hippocampal regions CA1 and CA3 using a rat model of global brain ischemia and reperfusion (I/R). D was estimated by quantifying protein aggregates using ubiquitin Western blotting. S was estimated by quantifying changes in polysomal mRNAs as measured by microarray chips. D and S time courses were sampled at 0.5, 8, 16, 24, 48, and 72 hrs of reperfusion after 10 min brain ischemia. CA1 dies and CA3 survives. The theory predicts D will be larger in CA1 and …

Calponin And Cytoskeleton Dynamics In Macrophage Functions And The Pathogenesis Of Atherosclerosis, Rong Liu

Wayne State University Dissertations

Arterial atherosclerosis is an inflammatory disease. Macrophages play a major role in the pathogenesis and progression of atherosclerotic lesions. Modulation of macrophage function is a therapeutic target for the treatment of atherosclerosis. Calponin is an actin-filament-associated regulatory protein that inhibits the activity of myosin-ATPase and dynamics of the actin cytoskeleton. Encoded by the Cnn2 gene, calponin isoform 2 is expressed at significant levels in macrophages. Deletion of calponin 2 increases macrophage migration and phagocytosis. In the present study, we investigated the effect of deletion of calponin 2 in macrophages on the pathogenesis and development of atherosclerosis. The results showed that …

Muscle Metaboreflex And Arterial Baroreflex: Action, Interaction And Altered Control In Heart Failure, Jasdeep Kaur

Wayne State University Dissertations

Stimulation of skeletal muscle afferents by metabolites that accumulate in the exercising muscle elicits a large pressor response, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal exercise induces large increases in arterial pressure, cardiac output, heart rate and ventricular contractility however, the vascular responses have varied in previous studies. We addressed three specific questions: 1) what are the mechanism(s) regulating the non-ischemic vasculature during muscle metaboreflex activation in normal subjects, 2) whether muscle metaboreflex activation vasoconstricts the ischemic active muscle from which this reflex originates and if this vasoconstriction is exaggerated in heart failure and 3) how do the …

An Analysis Of Plasticity In The Rat Respiratory System Following Cervical Spinal Cord Injury And The Application Of Nanotechnology To Induce Or Enhance Recovery Of Diaphragm Function, Janelle Lorien Walker

Wayne State University Dissertations

Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration.

WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

Role Of Secretory Granule Heterogeneity In Calcium-Triggered Exocytosis, Tejeshwar Rao

Wayne State University Dissertations

The sympathetic nervous system is activated by a variety of threats to organismal homeostasis. The adrenomedullary chromaffin cell is the core effector of sympathetic activity in the peripheral nervous system. By design, the chromaffin cell secretory response is mutable so that release can be rapidly tuned to drive context-dependent changes in physiological function. However, the mechanisms by which this tuning is achieved with such high temporal fidelity and context specificity remain unclear. This represents a major gap in our understanding of the sympatho-adrenal system since it is known to modify the function of nearly every organ system in the body. …

Unstable Ventilatory Control During Sleep After High Spinal Cord Injury: The Contribution Of Chemosensitivity And Hypoventilation, Amy Therese Bascom

Wayne State University Dissertations

ABSTRACT

UNSTABLE VENTILATORY CONTROL DURING SLEEP AFTER HIGH SPINAL CORD INJURY: THE CONTRIBUTION OF CHEMOSENSITIVITY AND HYPOVENTILATION

by

Amy T. Bascom

May 2015

Advisor: Dr. Harry G. Goshgarian

Major: Anatomy and Cell Biology

Degree: Doctor of Philosophy

A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. My studies had 2 aims: 1) to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able-bodied controls and 2) to determine the response of …

Investigation Of Whether Sedentary And Physically Active Conditions Lead To Altered Gabaergic Signaling In The Rvlm, Maryetta Donna Dombrowski

Wayne State University Dissertations

Investigation of whether sedentary and physically active conditions lead to altered GABAergic signaling in the RVLM

MD Dombrowski, and PJ Mueller

Department of Physiology, Wayne State University, School of Medicine, Detroit, MI

A sedentary lifestyle is a major risk for cardiovascular disease. Cardiovascular disease has been associated with elevated basal sympathetic nerve activity. The rostral ventrolateral medulla is a bilateral brainstem region that is an important for the control of resting and reflex control of sympathetic nerve activity and blood pressure. The activity of these neurons in this region is tonically inhibited by the neurotransmitter γ-butyric amino acid (GABA). Interestingly, …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

by

JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …

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 …

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 …

Mechanisms Of Persistent Translation Arrest Following Global Brain Ischemia And Reperfusion, Jill Theresa Jamison

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION

by

JILL T. JAMISON

December 2011

Advisor: Donald J. DeGracia, Ph.D.

Major: Physiology

Degree: Doctor of Philosophy

The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is …

Mechanisms Of Translation Arrest Following Focal Brain Ischemia, Monique K. Lewis

Wayne State University Dissertations

MECHANISMS OF TRANSLATION ARREST FOLLOWING FOCAL BRAIN

ISCHEMIA

by

MONIQUE K. LEWIS

August 2011

Advisor: Dr. Donald DeGracia

Major: Physiology

Degree: Doctor of Philosophy

The loss of blood flow to the brain is termed ischemia and the subsequent resumption of blood flow is termed reperfusion. Brain ischemia and reperfusion (I/R) occurs primarily following resuscitation from cardiac arrest and stroke and presents one of the most significant clinical challenges. At present, there are no clinically effective pharmacologic interventions to halt brain damage following I/R. The major Aim of this dissertation will be to investigate possible mechanisms involved in neuron death following …

The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White

Wayne State University Dissertations

Post-operative adhesion development occurs in the vast majority of patients following abdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bands may form within the first 5-7 days post-surgery and have the ability to cause a distortion in the normal anatomical positioning of abdominal organs. Consequently, adhesions are major contributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain. Physiological processes responsible for adhesion formation remain obscure though it is believed to involve cell migration, proliferation, and differentiation of several cell types including mesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released from these …

Effect Of Dimethylarginine Dimethylaminohydrolase In The Development Of Salt Sensitivity, Samar Abdulla Nasser

Wayne State University Dissertations

Salt sensitivity is associated with a rise in blood pressure (BP) occurring during sodium loading and/or a fall in BP during sodium restriction that exceeds random fluctuations in BP. Salt sensitivity is more common in African American than Caucasian hypertensives and is also present, in normotensive African Americans. The mechanism or mechanisms resulting in salt-sensitive hypertension are multiple and include both activation of the renin angiotensin system via increases in angiotensin II and reductions in the endogenous vasodilator, nitric oxide (NO). An important means of NO downregulation is through asymmetric dimethylarginine (ADMA), an endogenous NO inhibitor, which is largely metabolized …