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Cardiac Calsequestrin Phosphorylation And Trafficking In The Mammalian Cardiomyocyte, Timothy Mcfarland

Wayne State University Dissertations

Cardiac CSQ (CSQ2) is a multifaceted protein, capable of binding significant quantities of Ca2+ and altering ryanodine receptor activity at the junctional sarcoplasmic reticulum (SR). Little is known about the trafficking of CSQ2 from its unknown site of biosynthesis, which appears to be of importance as its structure changes in a trafficking-dependent manner in various types of heart failure. Through the use of multiple antibodies specific to classic rough ER markers, and with the creation of CSQ-DsRed tetramer fusion protein, we were able to establish a juxtanuclear localization of rough ER in cardiomyocytes. Using fluorescence confocal microscopy, the translocon complex …

Crystallographic, Molecular Dynamics, And Enzymatic Studies Of Multi-Drug Resistant Hiv-1 Protease And Implications For Structure Based Drug Design (Project 1); Crystallographic Studies Of Human Myelin Protein Zero (Project 2), Zhigang Liu

Wayne State University Dissertations

Under drug selection pressure, emerging mutations render HIV-1 protease drug resistance, leading to the therapy failure in anti-HIV treatment.Tthe multidrug-resistant 769 (MDR) HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, 90) is selected for the present study to understand drug resistance issue.

Ten additional mutations are introduced to MDR769 HIV-1 protease to study the structural influences brought by these mutations. We get crystal structures of four variants (I10V, A82F, A82S and A82T) of MDR769 HIV-1 protease. All these mutations fail to further open the flaps and expand the active site cavity of MDR769 …

Amphiregulin (Areg) And Epidermal Growth Factor (Egf): Disparate In Egfr Signaling And Trafficking, Andrea Jacqueline Baillo

Wayne State University Dissertations

We have previously shown that SUM-149 human breast cancer cells require an AREG/EGFR autocrine loop for cell proliferation. We also demonstrated that AREG can increase EGFR stability and promote EGFR localization to the plasma membrane. In the presented dissertation we successfully knocked-down AREG expression in SUM-149 cells by lenti-viral infection of AREG shRNA. In the absence of AREG expression, SUM-149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by western blot. Immunofluorescence and confocal microscopy showed that following AREG knock-down, EGFR continued to localize to the …

Muscle Metaboreflex Control Of Coronary Blood Flow And Ventricular Contractility During Dynamic Exercise In Normal And Heart Failure Conditions, Matthew Coutsos

Wayne State University Dissertations

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired left ventricular contractility, and large decreases in coronary vascular conductance are observed. The purpose of this dissertation is to determine whether the muscle metaboreflex-induced restraint of coronary vasodilation functionally limits coronary blood flow and …

Frazzled And Abelson Interact To Regulate The Actin Cytoskeleton In Drosophila, Bridget Elsa Varughese

Wayne State University Dissertations

Guidance receptors such as Frazzled affect cell shape and motility by directly or indirectly modulating the cytoskeleton. Fra is particularly needed for the formation of the posterior commissures in a developing Drosophila embryo. The cytoplasmic tyrosine kinase, Abelson Kinase (Abl) enhances the loss of commissures observed in fra mutant. Abl physically interacts with Frazzled to help guide commissural axons across the midline. Furthermore, the loss of commissural axons is only seen when the actin dynamics are perturbed. Abl is also known to regulate actin-dependent processes underlying formation of filopodia, microspikes and membrane ruffles. So, we established a Drosophila S2 cell …

Ctla-4 Transcriptional Activation: Regulation Of Induced Expression, Heather Gibson

Wayne State University Dissertations

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a T cell surface protein that is homologous to CD28 and binds to the B7 family of ligands. Unlike CD28, CTLA-4 interaction transmits a negative signal in T cells, leading to suppression of proliferation. CTLA-4 is constitutively expressed on regulatory T cells (Tregs) but is also inducible in effector T cells. The mechanisms driving transcriptional regulation of CTLA-4 are poorly understood. Our previous work identified a bona fide NFAT1 binding site in the proximal promoter for effector T cells. In addition, we found histone acetylation occurred after stimulation.

As a result of its role …

The Creative Content Programme And Audiovisual E-Platform: An Institutional Analysis Of Unesco's Influence On The Development Of Independent Documentary Content And Production Practice, Deborah Joanne James

Wayne State University Dissertations

This dissertation is an institutional analysis of two interrelated UNESCO (United Nations Education Science and Cultural Organization) activities. These include the Creative Content Programme, and the Audiovisual E-Platform, an online catalogue and social networking hub for independent filmmakers/media producers from the global South. Contained by these activities, the author focuses the multi-method approach on gender and access by (A) conducting an analysis of the composition of programs and practices of the Creative Content Programme and the E-Platform; (B) conducting textual analysis of documentary media and interviews with Diaspora women producers; and (C) participating in and observing community-based multimedia production …

Preparing The Young Offender For Return To Society: A Theoretical Evaluation Of Guyanese Juvenile Delinquents' Narratives Based On General Treatment Models, Bertlyn Gretna Reynolds

Wayne State University Dissertations

The site of the study is a co-educational detention center known as the New Opportunity Corps (NOC), located in a former British colony of South America, now known as Guyana. Forty- eight detainees of this institution, which is also legally designated a training school, were interviewed about their backgrounds, daily activities and plans for the future. These structured interviews were used to test the central tenets of Sociological theories with some bearing on crime. Some of the findings are presented in the form of narrative analysis which includes discussion of various factors likely to have caused their juvenile delinquency. Family …

Monitoring, Diagnosis, And Control For Advanced Anesthesia Management, Zhibin Tan

Wayne State University Dissertations

Modern anesthesia management is a comprehensive and the most critical issue in medical care. During the past dacades, a large amount of research works have been focused on the problems of monitoring anesthesia depth, modeling the dynamics of anesthesia patient for the purpose of control, prediction, and diagnosis.

Monitoring the anesthesia depth is not only for keeping the patient in adquate anesthesia level but also for preventing the patient from overdosing. Several EEG based indexes have been developed such as the BIS, and Entropy etc. for measuring depth. However, reports mentioned that those indexes in some cases fail in detecting …

Pleiotropic Regulatory Function Of The Lysr Family Transcriptional Regulator Cpsy During Streptococcus Iniae Systemic Infection, Jonathan Paul Allen

Wayne State University Dissertations

The ability of a pathogen to metabolically adapt to the local environment for optimal expression of virulence determinants is a continued area of research. Orthologs of the Streptococcus iniae LysR family regulator CpsY have been shown to regulate methionine biosynthesis and uptake pathways, but appear to influence expression of several virulence genes as well. A S. iniae mutant with an in-frame deletion of cpsY is highly attenuated in a zebrafish infection model. The cpsY deletion mutant displays a methionine-independent growth defect in serum, which differs from the methionine-dependent defect observed for orthologous mutants of S. mutans and S. agalactiae. …

Small Gtp-Binding Proteins In Insulin Secretion, Bhavaani Jayaram

Wayne State University Dissertations

Type 2 diabetes mellitus is marked by a substantial beta-cell failure which is characterized by defective insulin secretion and resistance to insulin. Understanding the molecular events leading to Glucose-stimulated insulin secretion [GSIS] might serve as therapeutic potential towards diabetes. GSIS involves interplay between small G-proteins and their regulatory factors. Herein, I tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide exchange factor [GEF] for the small G-protein Arf6, mediates the activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of downstream effectors. Salient features of my study are: [i] ARNO/Arf6 is expressed …

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 …

Multi-Objective Cultural Algorithms, Dapeng Liu

Wayne State University Dissertations

Evolutionary algorithms, including the Cultural Algorithms and other bio-inspired approaches are frequently used to solve problems that are not tractable for traditional approaches. Previously, research in the field of evolutionary optimization has focused on single-objective problems. On the contrary, most real-world problems involve more than one objective where these objectives may conflict with each other.

The newest implementation of the Cultural Algorithms to solve multi-objective optimization is named MOCAT. It is not the first time that the Cultural Algorithms have been used to solve multi-objective problems. Nonetheless, it is the first time that the Cultural Algorithms systematically merge techniques that …

Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma

Wayne State University Dissertations

During peripheral nervous system development, successful communication between axons and glial cells including Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system, is required for the proper functions of both neurons and glia. Three types of alternatively-spliced proteins belonging to the neuregulin1 (NRG1) gene family of growth and differentiation factors are essential for Schwann cell survival and peripheral nerve development. While membrane-bound NRG1 forms (type III) has been strongly implicated in the regulation of myelination process at late stage of Schwann cell development, little is known about the role of soluble, heparin-binding forms of NRG1 (type I/II) …

Mechanisms Of Regulation Of Islet Function By Nadph Oxidase, Ismail Syed

Wayne State University Dissertations

Glucose stimulated insulin secretion (GSIS) involves a series of metabolic and cationic events, leading to translocation of insulin-laden secretory granules from a distal site toward the plasma membrane for fusion and release of insulin into circulation. Vesicular transport and fusion events are tightly regulated by signals which coordinate between vesicle- and membrane-associated docking proteins. It is now being accepted that reactive oxygen species [ROS] plays a second messenger role in islet â-cell function. Further, evidence from multiple laboratories suggests a tonic increase in ROS generation is necessary for GSIS and fatty acid-induced insulin secretion. On the other hand, excessive ROS …

Reassembling Documentary: From Actuality To Virtuality, Emine Selmin Kara

Wayne State University Dissertations

At a period of intense technological change, which has led to an increasing degree of modularity in documentary media, "Reassembling Documentary: From Actuality to Virtuality" takes up episodic documentaries and non-fiction films broken into distinctly conceptualized parts, in order to examine how the evolution of technologies transform documentary film and media's relationship to the audiovisual archive across different historical periods. More specifically, the dissertation challenges the assumption that documentary film is essentially holistic in its discursive orientation and audiovisual aesthetics, by studying the fragmented works of a highly unique and international group of filmmakers, such as Harun Farocki, Werner Herzog, …

Deformable Meshes For Shape Recovery: Models And Applications, Chang Liu

Wayne State University Dissertations

With the advance of scanning and imaging technology, more and more 3D objects become available. Among them, deformable objects have gained increasing interests. They include medical instances such as organs, a sequence of objects in motion, and objects of similar shapes where a meaningful correspondence can be established between each other. Thus, it requires tools to store, compare, and retrieve them. Many of these operations depend on successful shape recovery. Shape recovery is the task to retrieve an object from the environment where its geometry is hidden or implicitly known. As a simple and versatile tool, mesh is widely used …

Expression Of Microbial Rhodopsins In Retinal Neurons With Subcellular Targeting Motifs: For The Study Of The Structure/Function Of Aii Amacrine Cells And For Vision Restoration, Chaowen Wu

Wayne State University Dissertations

Protein-targeting motifs serve as addresses for subcellular protein localization. This feature of targeting-motifs was used to study the retina. The first part of the dissertation reports in the axonless spiking AII amacrine cell of the mammalian retina a dendritic process sharing organizational and functional similarities with the axon initial segment, the typical site of action potential initiation. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP (ChR2-GFP) with the AIS-targeting motif of sodium channels (NavII-III) and was shown to be the site of spike initiation. The second part of the dissertation aimed to improve microbial rhodopsin-mediated gene therapy for vision …

Observational Study Of Children With Autism Who Have Participated In Hyperbaric Oxgen Therapy, Tamela Marie Powell

Wayne State University Dissertations

Autism is the fastest growing disability ever. With the growth comes a lot of questions as to the etiologies and treatment of this condition, often putting parents, schools, and traditional medical personnel at odds with what treatments have efficacy. As the popularity of alternative treatments increase, so does the need for research.

Hyperbaric oxygen therapy is one alternative treatment parents are seeking for their child with autism. When one looks at the science behind hyperbaric oxygen therapy and the physical condition of a child with autism the rationale behind the treatment becomes clear. Research has shown that children with autism …

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 …

Rox1 Function In Dosage Compensation: Structural / Functional Analysis Of A Non-Coding Rna, Ying Kong

Wayne State University Dissertations

roX1 is a long non-coding RNA involved in the chromosome-wide gene regulation that occurs during dosage compensation in Drosophila. Dosage compensation in Drosophila melanogaster occurs by a global two-fold increase of transcription from the single male X chromosome. This essential process compensates for X chromosome monosomy. The male-specific lethal (MSL) complex, containing five proteins, localizes to the male X chromosome and alters chromatin to modify gene expression. roX1 and roX2 RNAs are redundant components of MSL complex that are required for its exclusive X-localization. Recent studies in our lab have revealed a second role of roX RNAs in heterochromatic gene …

Slavery And Abortion: The Paradox Of American Liberalism, Mark A. Ladd

Wayne State University Dissertations

Louis Hartz proposed that America possesses a liberal tradition that works toward a Lockean equality for all people. I argue that Hartzs' theory is still applicable to America even though illiberal institutions have and do exist. My contention is that it is the paradox of liberalism that allows for this. Slavery is the quintessential illiberal institution, yet liberal concepts allowed it to exist in America for over 200 years. It is my contention that abortion is another illiberal institution that is being promoted by the paradox of liberalism. With the use of John Rawls theory of distributive justice abortion can …

Oxygen Limitation And Tissue Metabolic Potential Of The African Fish Barbus Neumayeri: Roles Of Native Habitat And Acclimatization, Martinez M. L, Raynard E. L, Bernard B. Rees, Chapman L. J

Biological Sciences Faculty Publications

Background: Oxygen availability in aquatic habitats is a major environmental factor influencing the ecology, behaviour, and physiology of fishes. This study evaluates the contribution of source population and hypoxic acclimatization of the African fish, Barbus neumayeri, in determining growth and tissue metabolic enzyme activities. Individuals were collected from two sites differing dramatically in concentration of dissolved oxygen (DO), Rwembaita Swamp (annual average DO 1.35 mgO2 L-1) and Inlet Stream West (annual average DO 5.58 mgO2 L-1) in Kibale National Park, Uganda, and reciprocally transplanted using a cage experiment in the field, allowing us to maintain individuals under natural conditions of …

Geographic Variation In The Effects Of Heat Exposure On Maximum Sprint Speed And Hsp70 Abundance In Populations Of The Western Fence Lizard, Scelopolus Occidentalis, D M. Mcmillan, D J. Irschick, Bernard B. Rees

Biological Sciences Faculty Publications

We examined whether western fence lizards Sceloporus occidentalis

occurring in thermally divergent environments display differential

responses to high temperature in locomotor performance

and heat-shock protein (Hsp) expression. We measured

maximum sprint speed in S. occidentalis from four populations

at paired latitudes and elevations before and after exposure to

an experimental heat treatment and then quantified hind-limb

muscle Hsp70 expression. Lizards collected from northern or

high-elevation collection sites suffered a greater reduction in

sprint speed after heat exposure than lizards collected from

southern or low-elevation sites. In addition, lizards from northern

collection sites also exhibited an increase in Hsp70 expression

after …

Impairment Of Na/K-Atpase Signaling In Renal Proximal Tubule Contributes To Dahl Salt-Sensitive Hypertension, Jiang Liu, Yanling Yan, Lijun Liu, Zijian Xie, Deepak Malhotra, Bina Joe, Joseph I. Shapiro

Pharmaceutical Science and Research

We have observed that, in renal proximal tubular cells, cardiotonic steroids such as ouabain in vitro signal through Na/K-ATPase, which results in inhibition of transepithelial 22Na transport by redistributing Na/K-ATPase and NHE3. In the present study, we investigate the role of Na/K-ATPase signaling in renal sodium excretion and blood pressure regulation in vivo. In Sprague-Dawley rats, high salt diet activated c-Src and induced redistribution of Na/K-ATPase and NHE3 in renal proximal tubules. In Dahl salt sensitive (S) and resistant (R) rats given high dietary salt, we found different effects on blood pressure but, more interestingly, different effects on renal salt …

International Advocate For Peace Award Acceptance Speech, Abigail E. Disney

Cardozo Journal of Conflict Resolution

In a few weeks, we will all be gathering around our mothers to celebrate one of the most shamelessly trumped-up, commercialized and corny-and I might add, one of my very favorite-holidays on the American calendar: Mother's Day. I do not want to sound cynical; it is truly a wonderful thing for us to stop and honor those women in our lives who have shaped us, for better or for worse. And who does not love a little tribute made out of glitter and doilies and Elmer's glue?

Modeling Connectivity Of Black Bears In A Desert Sky Island Archipelago, Todd C. Atwood, Julie K. Young, Jon P. Beckmann, Stewart W. Breck, Jennifer A. Fike, Olin E. Rhodes Jr., Kirby D. Bristow

United States Department of Agriculture Wildlife Services: Staff Publications

Landscape features such as rivers, mountains, desert basins, roads, and impermeable man-made structures may influence dispersal and gene flow among populations, thereby creating spatial structure across the landscape. In the US–Mexico borderland, urbanization and construction of the border fence have the potential to increase genetic subdivision and vulnerability to isolation in large mammal populations by bisecting movement corridors that have enabled dispersal between adjacent Sky Island mountain ranges. We examined genetic variation in black bears (Ursus americanus) from three regions in central and southern Arizona, US, to assess genetic and landscape connectivity in the US–Mexico border Sky Islands. We found …

Partitioning Of Anthropogenic Watering Sites By Desert Carnivores., Todd C. Atwood, Tricia L. Fry, Bruce Leland

United States Department of Agriculture Wildlife Services: Staff Publications

We investigated the role of water features as focal attractors for gray foxes (Urocyon cinereoargenteus), coyotes (Canis latrans), and bobcats (Felis rufus) in west Texas to determine if they were foci for interspecific interaction. Mixed effects models indicated that species partitioned use of water features spatially and temporally. Linear models indicated factors influencing relative activity at water features varied by species. For coyotes and bobcats, the water availability model, containing days since last rainfall and nearest-neighbor distance to water was best supported by the data, with relative activity increasing with time between rainfall and distance between waters. For gray foxes, …

Efficacy Of European Starling Control To Reduce Salmonella Enterica Contamination In A Concentrated Animal Feeding Operation In The Texas Panhandle, James C. Carlson, Richard M. Engeman, Doreene R. Hyatt, Rickey L. Gilliland, Thomas J. Deliberto, Larry Clark, Michael J. Bodenchuck, George M. Linz

United States Department of Agriculture Wildlife Services: Staff Publications

Background: European starlings (Sturnus vulgaris) are an invasive bird species known to cause damage to plant and animal agriculture. New evidence suggests starlings may also contribute to the maintenance and spread of diseases within livestock facilities. Identifying and mitigating the risk pathways that contribute to disease in livestock is necessary to reduce production losses and contamination of human food products. To better understand the impact starlings have on disease transmission to cattle we assessed the efficacy of starling control as a tool to reduce Salmonella enterica within a concentrated animal feeding operation. We matched a large facility, slated for operational …

Domestic Calf Mortality And Producer Detection Rates In The Mexican Wolf Recovery Area: Implications For Livestock Management And Carnivore Compensation Schemes., Stewart W. Breck, Bryan M. Kluever, Michael Panasci, John Oakleaf, Terry Johnson, Warren B. Ballard, Larry Howery, David L. Bergman

United States Department of Agriculture Wildlife Services: Staff Publications

Conserving large carnivores throughout the world will often require that they share the landscape with livestock. Minimizing depredations and increasing tolerance by livestock producers will be critical for conservation efforts. To investigate factors influencing calf mortality and producer detection rates (i.e., number of livestock killed by predators, found by producers, and correctly classified as to cause of death), we monitored radio-tagged domestic calves at two sites in the Mexican wolf recovery area (East Eagle [EE] and Adobe Ranch [AR]). Study areas differed in grazing practices, density of predators (mountain lions, black bears, coyotes, and Mexican wolves), and amount of effort …