Digital Commons Network^™

Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein

All ETDs from UAB

Cystic fibrosis (CF) is caused by mutation of one protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which normally functions as a chloride channel at the apical surface of epithelial cells. The most common CFTR mutation results in the deletion of a single amino acid (phenylalanine) at position 508, which causes the protein to fold improperly. The ΔF508 CFTR is a temperature-sensitive (TS) processing mutant: At the restrictive temperature, 37°C, ΔF508 CFTR misfolds in the endoplasmic reticulum (ER) and is degraded, but at the permissive temperature, 27°C, it is “rescued” from degradation (rΔF508). In particular, rΔF508 CFTR folds correctly enough …

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

All ETDs from UAB

The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …

Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock

All ETDs from UAB

The heme oxygenase-1 (HO-1) gene encodes a microsomal enzyme that catalyzes the conversion of heme to carbon monoxide, Iron, and biliverdin. HO-1 transcription is induced upon a plethora of cellular stresses including heme, heavy metal exposure, hy-poxia, oxidative stress and many others. The goal of this work was to explore the molecu-lar regulation of HO-1 transcription. Four DNase 1 hypersensitive sites are detected within the HO-1 promoter extending from ~-40bp to ~-9.2kb relative to the transcription start site. Dimethylsulfate (DMS) in vivo footprinting is shown for two regulatory re-gions and reveals nine protected guanines in all. Mutational analyses indicates that …

Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood

All ETDs from UAB

The human immunodeficiency virus (HIV) pandemic is a growing concern, affecting almost 40 million people worldwide. Treatment for HIV infection consists of highly active antiretroviral therapy (HAART) to block different steps in the viral lifecycle, ultimately reducing HIV RNA to undetectable levels in the plasma. However, HIV RNA can be detected in numerous reservoirs outside of the blood despite the use of HAART. Therefore, measurement of antiretroviral (ARV) drugs in other biological matrices is important to broaden our understanding of HIV transmission, the development of viral resistance with sub-optimal ARV exposure, and fetal and neonatal drug exposure. This work describes …

The Role Of Complement In The Clearance Of Streptococcus Pneumoniae Through Immune Adherence, Jie Li

All ETDs from UAB

Streptococcus pneumoniae is the most frequently isolated pathogen causing bacteremia in young children and elderly adults. Complement-dependent opsonophagocytosis is thought to be essential to eliminate pneumococci from the circulation. Pneumococci are reported to attach to erythrocytes through immune adherence (IA), a complement and antibody- dependent process that facilitates phagocytosis of pneumococci. In these studies we have determined that protein (chapter 1) and polysaccharide (chapter 2) virulence factors of pneumococci can interfere with this process and that antibody to pneumococci can enhance this process. Using PspA and/or PspC negative strains and complement-deficient mouse sera, we demonstrated that PspA inhibits complement C1q …

A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas

All ETDs from UAB

The aim of this work was to build an understanding of the protein/protein interactions involved in HIV-1 capsid assembly as it relates to the condensation of capsid within the virion. This was undertaken in an attempt to (i) understand how capsid subunits recognize and interact with each other, (ii) gain insight into the protein-protein interactions involved in the process, and (iii) determine if the protein-protein interactions involved in virus cap-sid assembly can be used as a target for viral inhibition. Within this dissertation you will find two approaches to this investigation. The first examines the role of electrostatics in the …

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

All ETDs from UAB

Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni

All ETDs from UAB

Reverse transcription is the hallmark of retroviruses, such as HIV-1. A cellular tRNA bound to the primer binding site region (PBS) is used for initiation of reverse transcription. HIV-1 specially selects tRNALys3 as primer, although changing the PBS can force HIV-1 to use alternative tRNAs as a primer. However, HIV-1 reverts back to use tRNALys3 following in vitro replication. The A-loop, located upstream of PBS, interacts with the anti-codon of primer tRNA. The inclusion of A-loop modification has been shown to stabilize the utilization of some alternative tRNAs. The studies in this dissertation focus on further defining the role of …

Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie

All ETDs from UAB

ErbB receptor tyrosine kinases have long been implicated in cancer formation and progression by regulating cell division, migration, and survival. ErbBs are also essential in multiple processes during invertebrate development; however, their activities during vertebrate embryogenesis are not well understood. For functional characterization of ErbB signaling during vertebrate development, frog model Xenopus laevis was used in our studies. The expression pattern and the general activities of ErbB receptors during early frog development were first analyzed and results shown that ErbBs regulate gastrulation, somite organization and head patterning. As gastrulation is the first major morphogenetic event in vertebrate development, I focused …

Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang

All ETDs from UAB

A gyrase mutant strain (gyrB652) has severe growth defect at 42°C. The survival at high temperature is dependent on DNA repair proteins. The purified mutant gyrase was assayed for supercoiling acitivity and quinolone-induced DNA cleavage activity. The results suggested that the mutant enzyme is not temperature-sensitive, but has slower kinetics than the wild type gyrase. The DNA supercoiling levels at multiple chromosomal loci in exponential phase cells were monitored with γδ resolvase-mediated recombination assay. The wild type cells showed homogenous supercoiling levels throughout most of the chromosome. But the superhelicity at dif locus was significantly lower than the other loci. …

The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read

All ETDs from UAB

The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium. Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom …

Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki

All ETDs from UAB

The use of Bacillus anthracis as a bioweapon depends on the dispersal of its spores into the environment, entrance into the body, spore uptake by human host cells, germination of the spores in the host and the pathological consequences of the virulence factors produced by the vegetative cells. Prior to 2001, very little was known about the mechanisms of spore entry into the host, including targeting cell types at airway, digestive and skin surfaces, potential spore receptors on these cells and spore encounters with cellular and humoral elements of the innate and adaptive immune systems. To this end, we have …

Relaxation Rate-Based Magnetic Resonance Imaging Quantification Of Myocardial Infarction, Pal Suranyi

All ETDs from UAB

Ischemic heart disease is the leading cause of mortality in western societies. Treatment needs to be tailored for each individual, which requires accurate assessment of the underlying pathology. Magnetic Resonance Imaging (MRI) is a relatively young modality in the field of cardiovascular imaging, and boasts with the lack of harmful radiation, excellent soft tissue contrast, and high spatial-temporal resolution. The very foundation of the concept of MRI was the finding that pathology causes changes in the relaxation rates of tissues. Measurement of relaxation rates is more time consuming than generating simple signal intensity images weighted by the longitudinal or transverse …

The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis, Robert C. Axtell

All ETDs from UAB

The regulation of activation, differentiation and persistence of effector T-cells are critical for the development of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Until now, the function of CD5 was accepted to be a negative regulator of T-cell activation. This dissertation reports that CD5 has an addi-tional role in T-cell responses, which is to promote cell survival. Observations from EAE experiments revealed that mice deficient in CD5 exhibited decreased disease severity which was associated with the inability of activated T-cells to survive. Moreover, block-ing the engagement of CD5 in mice led to enhanced activation induced cell death …

Exploration Of Computational Methods For Classification Of Movement Intention During Human Voluntary Movement From Single Trial Eeg, Ou Bai, Peter Lin, Sherry Vorbach, Jiang Li, Steve Furlani, Mark Hallett

Electrical & Computer Engineering Faculty Publications

Objective: To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG).

Methods: Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis …

A Proteome-Wide Protein Interaction Map For Campylobacter Jejuni, Jodi R. Parrish, Jingkai Yu, Guozhen Liu, Julie A. Hines, Jason E. Chan, Bernie A. Mangiola, Huamei Zhang, Svetlana Pacifico, Farshad Fotouhi, Victor J. Dirita, Trey Ideker, Phillip Andrews, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Data from large-scale protein interaction screens for humans and model eukaryotes have been invaluable for developing systems-level models of biological processes. Despite this value, only a limited amount of interaction data is available for prokaryotes. Here we report the systematic identification of protein interactions for the bacterium Campylobacter jejuni, a food-borne pathogen and a major cause of gastroenteritis worldwide.

Results

Using high-throughput yeast two-hybrid screens we detected and reproduced 11,687 interactions. The resulting interaction map includes 80% of the predicted C. jejuni NCTC11168 proteins and places a large number of poorly characterized proteins into networks that provide initial …

Faculty Publications 2006, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 638 publications.

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …

Department Of Pathology, Thomas Jefferson University, Identification Of Conserved Gene Expression Features Between Murine Mammary Carcinoma Models And Human Breast Tumors., Jason I Herschkowitz, Karl Simin, Victor J Weigman, Igor Mikaelian, Jerry Usary, Zhiyuan Hu, Karen E Rasmussen, Laundette P Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G Backlund, Yuzhi Yin, Andrey I Khramtsov, Roy Bastein, John Quackenbush, Robert I Glazer, Powel H Brown, Jeffrey E Green, Levy Kopelovich, Priscilla A Furth, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard, Gary A Churchill, Terry Van Dyke, Charles M Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of …

Ribosome Recycling: An Essential Process Of Protein Synthesis, Michael C. Kiel, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

A preponderance of textbooks outlines cellular protein synthesis (translation) in three basic steps: initiation, elongation, and termination. However, researchers in the field of translation accept that a vital fourth step exists; this fourth step is called ribosome recycling. Ribosome recycling occurs after the nascent polypeptide has been released during the termination step. Despite the release of the polypeptide, ribosomes remain bound to the mRNA and tRNA. It is only during the fourth step of translation that ribosomes are ultimately released from the mRNA, split into subunits, and are free to bind new mRNA, thus the term "ribosome recycling." This step …

Appl1 Associates With Trka And Gipc1 And Is Required For Nerve Growth Factor-Mediated Signal Transduction, D. C. Lin, C. Quevedo, N. E. Brewer, A. Bell, J. R. Testa, Mark L. Grimes, F. D. Miller, D. R. Kaplan

Biomedical and Pharmaceutical Sciences Faculty Publications

The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA coirnmunoprecipitated in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 …

Donor Tricuspid Annuloplasty During Orthotopic Heart Transplantation: Long-Term Results Of A Prospective Controlled Study, Valluvan Jeevanandum, Hyde Russell, Paul Mather, Satoshi Furukawa, Allen Anderson, Jaishankar Raman

Department of Medicine Faculty Papers

Background: Development of tricuspid regurgitation after orthotopic heart transplantation can cause heart failure along with renal and hepatic impairment and portends a poor prognosis. If tricuspid regurgitation causes significant symptoms, tricuspid valve repair or replacement is often required. This study was designed to study the effects of prophylactic tricuspid valve annuloplasty (TVA) during orthotopic heart transplantation on long-term survival, renal function, and amount of tricuspid regurgitation.

Methods: Between April 1997 and March 1998, 60 patients (aged 18 to 70 years; 22 female) randomly received either standard bicaval orthotopic heart transplantation (group STD; n = 30) or bicaval orthotopic …

Multiple Domains In Siz Sumo Ligases Contribute To Substrate Selectivity., Alison Reindle, Irina Belichenko, Gwendolyn R Bylebyl, Xiaole L Chen, Nishant Gandhi, Erica S Johnson

Department of Biochemistry and Molecular Biology Faculty Papers

Saccharomyces cerevisiae contains two Siz/PIAS SUMO E3 ligases, Siz1 and Siz2/Nfi1, and one other known ligase, Mms21. Although ubiquitin ligases are highly substrate-specific, the degree to which SUMO ligases target distinct sets of substrates is unknown. Here we show that although Siz1 and Siz2 each have unique substrates in vivo, sumoylation of many substrates can be stimulated by either protein. Furthermore, in the absence of both Siz proteins, many of the same substrates are still sumoylated at low levels. Some of this residual sumoylation depends on MMS21. Siz1 targets its unique substrates through at least two distinct domains. Sumoylation of …

Soluble Amyloid Oligomers Increase Bilayer Conductance By Altering Dielectric Structure, Yuri Sokolov, J. Ashot Kozak, Rakez Kayed, Alexandr Chanturiya, Charles G. Glabe, James E. Hall

Neuroscience, Cell Biology & Physiology Faculty Publications

The amyloid hypothesis of Alzheimer's toxicity has undergone a resurgence with increasing evidence that it is not amyloid fibrils but a smaller oligomeric species that produces the deleterious results. In this paper we address the mechanism of this toxicity. Only oligomers increase the conductance of lipid bilayers and patch-clamped mammalian cells, producing almost identical current-voltage curves in both preparations. Oligomers increase the conductance of the bare bilayer, the cation conductance induced by nonactin, and the anion conductance induced by tetraphenyl borate. Negative charge reduces the sensitivity of the membrane to amyloid, but cholesterol has little effect. In contrast, the area …

Neuromechanics Of Multifunctionality During Rejection In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

How are the same muscles and neurons used to generate qualitatively different behaviors? We studied this question by analyzing the biomechanical and neural mechanisms of rejection responses in the marine mollusk Aplysia californica and compared these mechanisms with those used to generate swallowing responses (Ye et al., 2006). During rejection, the central grasper of the feeding structure closes to push inedible food out of the buccal cavity. This contrasts with swallowing, during which the grasper is open as it moves toward the jaws (protracts). We examined how the shape change of the grasper during rejection mechanically reconfigured the surrounding musculature. …

Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley

UNLV Magazine

No abstract provided.

A Survey Of Primary Care Residents Regarding Knowledge Of Hepatitis C, Joseph L. Yozviak Do, Facp, Erini Vasiliadis Do, Sharon R. Kimmel Phd, Mha, Suzanne J. Templer Do, Margaret Hoffman-Terry Md, Facp

Department of Medicine

No abstract provided.

Locus Ceruleus Regulates Sensory Encoding By Neurons And Networks In Waking Animals, David M. Devilbiss, Michelle E. Page, Barry D. Waterhouse

Department of Neurosurgery Faculty Papers

Substantial evidence indicates that the locus ceruleus (LC)–norepinephrine (NE) projection system regulates behavioral state and state-dependent processing of sensory information. Tonic LC discharge (0.1–5.0 Hz) is correlated with levels of arousal and demonstrates an optimal firing rate during good performance in a sustained attention task. In addition, studies have shown that locally applied NE or LC stimulation can modulate the responsiveness of neurons, including those in the thalamus, to nonmonoaminergic synaptic inputs. Many recent investigations further indicate that within sensory relay circuits of the thalamus both general and specific features of sensory information are represented within the collective firing patterns …

Silica-Coated Lanthanum-Strontium Manganites For Hyperthermia Treatments, Vuk Uskoković, Aljoša Košak, Miha Drofenik

Pharmacy Faculty Articles and Research

La_0.76Sr_0.24MnO_{3 + δ} particles, prepared by performing a traditional, solid-state method of synthesis, were coated by uniform layers of silica via initiating hydrolysis and condensation of TEOS in aqueous–alcoholic alkali environment. The eventually obtained samples exhibited Curie temperature at ∼40 °C, and comprised core-shell particles of ∼250 nm in diameter. By varying stoichiometric ratio of cations within manganite cores of the particles, Curie point of the resulting material can be varied too, thus opening a way for the simple design of biocompatible, temperature-self-regulating particles for application in hyperthermia treatments, with Curie point thereof adjusted to …

Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86^−/− mice. In the …