Digital Commons Network^™

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Myelin basic protein (MBP) is a major candidate autoantigen in multiple sclerosis (MS). Its immunodominant epitope, MBP 85–99, forms a complex with human leukocyte antigen (HLA)-DR2 with which multiple sclerosis is genetically associated. Copolymer 1 (Copaxone), a random amino acid copolymer [poly (Y,E,A,K)n] as well as two modified synthetic copolymers [poly (F,Y,A,K)n and poly (V,W,A,K)n] also form complexes with HLA-DR2 (DRA DRB1*1501) and compete with MBP 85–99 for binding. Moreover, two high-affinity synthetic peptide 15-mers that could inhibit binding even more effectively were previously designed. Here, we show that further-modified peptide 15-mers inhibited even more strongly (in order J5 > J3 …

The Genetics Of Ray Pattern Variation In Caenorhabditis Briggsae, Scott Everet Baird, Cynthia R. Davidson, Justin C. Bohrer

Biological Sciences Faculty Publications

Background: How does intraspecific variation relate to macroevolutionary change in morphology? This question can be addressed in species in which derived characters are present but not fixed. In rhabditid nematodes, the arrangement of the nine bilateral pairs of peripheral sense organs (rays) in tails of males is often the most highly divergent character between species. The development of ray pattern involves inputs from hometic gene expression patterns, TGFβ signalling, Wnt signalling, and other genetic pathways. In Caenorhabditis briggsae, strain-specific variation in ray pattern has provided an entrée into the evolution of ray pattern. Some strains were fixed for a derived …

Prenatal Stress And Stress Physiology Influences Human Fetal And Infant Development, Elyssia Poggi Davis, Calvin J. Hobel, Curt A. Sandman, Laura M. Glynn, Pathik D. Wadhwa

Psychology Faculty Books and Book Chapters

"Prenatal stress has been proposed as a risk factor that may have developmental consequences persisting throughout the lifespan. Exposing rodents to stress during pregnancy has consequences for brain development, stress regulation, learning, emotionality (increased anxiety), and social behavior (increased withdrawal) of the offspring (Weinstock, 2001; Chapillon et al., 2002). Additionally, non-human primates who experience stress during pregnancy have offspring with enhanced behavioral reactivity to stressors later in life (Clarke et al., 1994), lowered levels of motor behavior (Schneider, 1992), compromised neuromotor responses (Schneider and Coe, 1993), irritable temperament (Schneider et al., 1992), and attentional problems (Schneider et …

Effects Of Aging On Pressure-Induced Mapk Activation In The Rat Aorta, Kevin M. Rice

Theses, Dissertations and Capstones

With age, the cardiovascular system experiences substantial alterations in cellular morphology and function. The factors regulating these changes are unknown; however, the mitogen activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6 month old), aged (30 month old) and very aged (36 month old) Fischer 344 x Brown Norway F1 Hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11% …

Mechanisms Of Growth Hormone Enhancement Of Excitatory Synaptic Transmission In Hippocampus, Ghada Saad Zaglool Ahmed Mahmoud

Theses, Dissertations and Capstones

Growth hormone (GH) deficiency is associated with impaired learning and memory. One possible target for GH effects on memory is the hippocampus, a brain region containing GH receptors (GHRs). To determine if GH acutely alters hippocampal function, recombinant human GH (rhGH) was applied to in vitro rat hippocampal brain slices. Extracellular recordings were used to assess effects of GH on the field EPSP (fEPSP) and long-term potentiation (LTP) of the fEPSP. GHR expression was measured in GH-treated and control rat hippocampal slices using RT-PCR. The GH signaling pathway was investigated by studying the effect of GH on the fEPSP after …

Discovering The Barriers To Health-Promoting Lifestyles Among Appalachian Veterans With Uncontrolled Hypertension, Tara L. Porter

Theses, Dissertations and Capstones

Introduction: The purpose of this study was to discover the barriers to health promoting lifestyles among the Appalachian veteran population with uncontrolled hypertension.

Design: A quantitative research study was conducted over five months using a non-experimental, descriptive research design. Pender’s Health Promotion Model served as the study’s framework. Subjects were recruited from a primary care setting through advertisement within the hospital. A convenience sample of thirty-two subjects was obtained.

Method: The Health Promotion Lifestyle Profile (HPLP) II survey assessed for barriers to controlled hypertension in the following areas: health-promoting lifestyle, health responsibility, stress management, spiritual growth, interpersonal relationships, nutrition, and …

Effects Of Tamoxifen On Mitochondrial Nos Activity: Alteration In The Intramitochondrial Ca2+ Homeostasis, Sandeep S. Joshi

Theses, Dissertations and Capstones

Tamoxifen (Tam) is an anticancer drug that induces oxidative stress and apoptosis via mitochondria- and nitric oxide (NO)-dependent pathways. Here, we report that therapeutic concentrations of Tam stimulate the mitochondrial NO synthase (mtNOS) activity of isolated rat liver mitochondria by increasing the intramitochondrial ionized Ca²⁺ concentration ([Ca²⁺]_m). Tam decreases transmembrane potential (∆ψ) due to increased [Ca²⁺]_m that neutralizes the negative charges of the inner mitochondrial membrane. Thus, the present study reports a novel mechanism for the widely used anti- caner drug, Tam.

Setting Fires To Stem Cell Research, Roxanne Greitz Miller

Education Faculty Articles and Research

The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few science texts contain stem cell information, and those that do are generally written at a reading level above that of a typical middle grade student. In the lesson, students are introduced to the FIRES strategy and given an opportunity to evaluate stem cell information from …

Effect Of Dna Base Modification On Polymerase Chain Reaction Efficiency And Fidelity, Jan A. Sikorsky

Theses, Dissertations and Capstones

Polymerase stop assays, used to quantify DNA damage, assume single lesions are sufficient to block thermostable DNA polymerase progression. To explore this assumption, 90 base oligonucleotides containing normal or modified DNA bases were amplified using real-time PCR. Data implied that the PCR efficiency was influenced to differing degrees depending on which base lesion was present on the input oligonucleotide; specifically, while reactions with templates containing a single 8-oxo-7,8-dihydro-2í-deoxyguanosine (8-oxodG) were not noticeably altered, the presence of a single 8-oxo-7,8-dihydro-2í-deoxyadenosine, an abasic site, or a cis-syn thymidine dimer (TT dimer) dramatically delayed amplification. In addition, the presence of two tandem 8-oxodGs …

Synthesis Of Intermediates Of Receptor-Subtype Selective Lpa Antagonists, Danielle Zafrane

Theses & Honors Papers

It has been shown that 1-oleoyl lysophosphatid ic acid (LPA; 1-acyl-2-glycerol-3-phosphate) plays a vital role in the progression and proliferation of ovarian cancer. The design and synthesis of LPA receptor selective agonists and antagonists has been the focus of intense research within the last ten years .¹ During the Research Experience for Undergraduate s (REU) internship at the University of Virginia 4-bromo-2-(hydroxymethyl)pyridine (intermediate 43) was designed and synthesized based on earlier results. Intermediate 43 was used to modify a current LPA analogue. Modification of current LPA analogues may result in the discovery of potent and metabolically stable LPA antagonists …

Gene Expression Profiling Revealed Novel Mechanism Of Action Of Taxotere And Furtulon In Prostate Cancer Cells, Yiwei Li, Maha Hussain, Sarah H. Sarkar, James Eliason, Ran Li, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.

Methods

The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot …

Expression Pattern And Regulation Of Genes Differ Between Fibroblasts Of Adhesion And Normal Human Peritoneum, Ujjwal K. Rout, Ghassan M. Saed, Michael P. Diamond

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, it is imperative that we understand the mechanisms of adhesion formation to prevent its occurrence. This requires thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in the formation of adhesion tissues. Therefore, identifying changes …

Effect Of Genetic Variation On The Formation Of Hepatocarcinogenic Metabolites Of Trichloroethylene Using Chloral Hydrate Studies (An Interdisciplinary Approach), Apryl Bronley-Delancey

MUSC Theses and Dissertations

Trichloroethylene (TCE) is listed with the EPA as a suspected human carcinogen and is ubiquitous in the environment (US EPA 1992). Chloral hydrate (CH) is a sedative drug and a cytochrome P450 (CYP 450)-derived metabolite of TCE (Klaassen 2001). Chloral hydrate is metabolized in the liver to the rodent hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH), and to the non-carcinogenic metabolite trichloroethanol (TCEOH) by alcohol dehydrogenase (ADH) (Klaassen 2001). Both ALDH and ADH are polymorphic in humans which can presumably predict the disposition of chloral hydrate into the carcinogenic vs. non-carcinogenic pathways. The likelihood is then raised that subpopulations of …

Vertebrate Gld2 Poly(A) Polymerases In The Germline And The Brain, Labib Rouhana, Liaoteng Wang, Natascha Buter, Jae Eun Kwak, Craig A. Schiltz, Tania Gonzalez, Ann E. Kelley, Charles F. Landry, Marvin Wickens

Biological Sciences Faculty Publications

Cytoplasmic polyadenylation is important in the control of mRNA stability and translation, and for early animal development and synaptic plasticity. Here, we focus on vertebrate poly(A) polymerases that are members of the recently described GLD2 family. We identify and characterize two closely related GLD2 proteins in Xenopus oocytes, and show that they possess PAP activity in vivo and in vitro and that they bind known polyadenylation factors and mRNAs known to receive poly(A) during development. We propose that at least two distinct polyadenylation complexes exist in Xenopus oocytes, one of which contains GLD2; the other, maskin and Pumilio. GLD2 protein …

Punishment And Rehabilitation Views Of Social Work Majors And Non-Social Work Students: An Exploratory Study, Eric G. Lambert, Sudershan Pasupuleti, Reva I. Allen

Journal of the South Carolina Academy of Science

No abstract provided.

Design And Cloning Of A Hammerhead Ribozyme Targeted Tohiv-1p7fmrna, Katherine L. Anderson, William H. Jackson

Journal of the South Carolina Academy of Science

No abstract provided.

Mutation Analysis By The Use Of Temporal Temperature Gradient Gel Electrophoresis, Özgül M. Alper, Güven Lüleci̇, Lee-Jun C. Wong

Turkish Journal of Medical Sciences

ALPER^1, Güven LÜLECİ^1, Lee-Jun C. WONG^2 ^1 Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya - Turkey ^2 Georgetown University Medical Center Institute for Human and Molecular Genetics, Washington, DC - USA

A Comparison Of Three High Performance Liquid Chromatographic (Hplc) Methods For Measurement Of Plasma Total Homocysteine, Emi̇n Özgür Akgül, Erdi̇nç Çakir, Ömer Özcan, Hali̇l Yaman, Cumhur Bi̇lgi̇, Mehmet Kemal Erbi̇l

Turkish Journal of Medical Sciences

Homocysteine (tHcy) has been in routine use in many centers after this amino acid was reported as an independent risk factor for cardiovascular, cerebrovascular and peripheral vascular diseases. Many high-performance liquid chromatographic (HPLC) methods including a commercially available kit (Chromsystems) were reported for measuring tHcy in biologic samples. Although the commercial kits are believed to have higher precision, sensitivity and accuracy as well as practical and fast, it may cause high prices by increased test ordering. In this study we aimed to compare two different low-cost methods which had similar advantages with commercial kit as a reference method. In the …

Tsh Levels In Turkish Adults: Prevalences And Associations With Serum Lipids, Coronary Heart Disease And Metabolic Syndrome, Gülay Hergenç, Altan Onat, Si̇nan Albayrak, Ahmet Karabulut, Serdar Türkmen, İbrahi̇m Sari, Günay Can

Turkish Journal of Medical Sciences

Overt hypothyroidism is implicated in atherosclerosis through dyslipidemia, hypertension, and hyperhomoscysteinemia. Epidemiological data related to the role of thyroid hormones in the risk of coronary heart disease (CHD) and metabolic syndrome (MS) in Turkish adults are lacking. Thyroid stimulating hormone (TSH) was measured in the 2004 follow-up of the Turkish Adult Risk Factor Study, with the aim of investigating thyroid hormone status as a possible risk factor in CHD and MS in the population sample. To this end, a subgroup of the cohort (512 men and women: mean age 52 ± 11.4) in whom the prevalences for CHD, MS and …

Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted …

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …

The Pericentrion: Identification, Characterization, And Function Of A Novel Cpkc-Dependent Compartment, Kevin P. Becker

MUSC Theses and Dissertations

Members of the protein kinase C (PKC) superfamily transduce a myriad of transmembrane signals initiated by the formation of sn-l ,2-diacylglycerol (DAG). As the primary physiological agonist for C] domain containing PKC isoenzymes, DAG functions to regulate the spatial and temporal parameters of PKC activity. It is now recognized that cellular DAG levels can vary from minutes to hours and even days. These observations have suggested a division of PKC functions that correlate to the duration of the cellular DAG signal. In their classical role, cPKCs respond acutely to the short-lived (1-2 min) DAG generated at the plasma membrane by …

The Effect Of Antioxidant Supplementation On Human Sperm Cryopreservation, Katrina E. Taylor

Theses : Honours

Semen cryopreservation has an important role in assisted reproductive technology however, the cooling, freezing and thawing processes often result in a significant loss of sperm motility, viability and nuclear integrity. The destructive effects of cryopreservation are significantly exacerbated in samples exhibiting low sperm number and poor morphological characteristics. Recent research into infertility has focused on the correlation between excessive oxidation and subfertility, in particular radical induced lipid peroxidation within the phospholipid bilayer of the spermatozoon plasma membrane and the promotion of cellular damage as a result of antioxidant insufficiency. The aim of this study was to evaluate the effect of …

Mechanism Of Cancer Selective Apoptosis By Par-4, Sushma Gurumurthy

University of Kentucky Doctoral Dissertations

Despite distinct dissimilarities, diverse cancers express several common pro-tumorigenic traits. We present here evidence that the pro-apoptotic protein Par-4 utilizes one such common tumorigenic trait to become selectively activated and induce apoptosis in cancer cells. Elevated PKA activity noted in cancer cells activated the apoptotic function of ectopic Par-4 or its SAC domain, which induces apoptosis selectively in cancer cells and not in normal or immortalized cells. PKA preferentially phosphorylated Par-4 at the T155 residue within the SAC domain in cancer cells. Moreover, pharmacological-, peptide- or siRNA-mediated inhibition of PKA activity in cancer cells resulted in abrogation of both T155 …

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …

Association Between Coinfection Of Porphyromonas Gingivalis, Actinobacillus Actinomycetemcomitans And Treponema Denticola And Periodontal Tissue Destruction In Chronic Periodontitis, L. L. Chen, Y. M. Wu, J. Yan, W. L. Sun, Y. Z. Sun, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

No abstract provided.

Replication And Encapsidation Of Papillomaviruses In Saccharomyces Cerevisiae, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Improvements in methodologies to recapitulate and study particular biological functions of the

papillomavirus life cycle have led to great advances in our knowledge of these viruses. Described in

this chapter are techniques that allow low-copy and high-copy replication of full-length human

papillomavirus (HPV) genomes, as well as assembly of virus-like particles, in Saccharomyces

cerevisiae (yeast). This system has several distinct advantages that make it an attractive complement

to the well-established raft-culturing system. First, yeast are inexpensive, rapid, and simple to culture

in the lab. Second, they provide an ever-widening array of genetic tools to analyze HPV functions

—most recently notable, …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …