Digital Commons Network^™

The Integrated Biomedical Science Graduate Program At The University Of South Carolina, Richard Hunt

Journal of the South Carolina Academy of Science

No abstract provided.

Synthesis Of Fatty Acid Binding Protein Inhibitors: A New Approach For Diabetes Treatment, Shekelia Baccus, M. Perry Davis Jr, David R. Magnin

Journal of the South Carolina Academy of Science

No abstract provided.

Generation Of A Retroviral Vector That Expresses An Anti-Hiv-1 Tat Hammerhead Ribozyme, Lindsey E. Padgett, William H. Jackson

Journal of the South Carolina Academy of Science

No abstract provided.

The Effect Of Incubation Time On The Generation Of Benzene In Sierra Mist Free, Sarah Law

Journal of the South Carolina Academy of Science

No abstract provided.

Downregulation Of Hiv-1 Vif By A Hammerhead Ribozyme Expressed From A Retroviral Vector, Audrey M. Hendley, William Jackson

Journal of the South Carolina Academy of Science

No abstract provided.

Temperature Changes Resulting From A Gaalas Laser In The Decontamination Of A Failing Dental Implant, Adam B. Oppenheimer

Journal of the South Carolina Academy of Science

No abstract provided.

Where Do Mouse Embryos Thrive Best? Comparison Of Mammalian Embryo Development Under Varying Laboratory Environments, Yvonne K. Kao, H. Lee Higdon Iii, Ph.D, Jennifer E. Graves-Herring , M.S., William R. Boone Ph.D

Journal of the South Carolina Academy of Science

No abstract provided.

Metabolomic Investigation Of A New Rat Model Of Autosomal Recessive Polycystic Kidney Disease, Hayley White

Theses : Honours

Metabolomics is complementary to genomics, transcriptomics and proteomics; however, it has the capacity to reflect the activities of the organism at a functional level. Metabolomics can therefore be used as a diagnostic tool by identifying the up- or down-regulation of metabolites in the cell, tissue, plasma, serum or urine. Specifically, these are, but are not limited to, identifying biomarkers of disease, monitoring drug treatments, and monitoring surgical procedures such as organ transplant. Autosomal recessive polycystic kidney disease (ARPKD) makes up 5-8% of patients requiring kidney dialysis and/or transplantation and of these, an estimated 50% of patients progress to end-stage renal …

Role Of Mel-18 In Regulating Protein Sumoylation And Identification Of A New Polymorphism In Bmi-1, Jie Zhang

University of Kentucky Doctoral Dissertations

Small ubiquitin-like modifier (SUMO) regulates numerous biological functions. In a previous study we found that sumoylation of HSF2 is involved in regulating HSF2 bookmarking function, but the mechanism that mediates this regulation was unknown. The results in my work support the intriguing hypothesis that polycomb protein, Mel-18, actually functions as an anti-SUMO E3 protein, interacting both with HSF2 and the SUMO E2 Ubc9, but acting to inhibit Ubc9 activity and thereby decrease sumoylation of the HSF2.

This study also suggested that Mel-18 negatively regulates the sumoylation of other cellular proteins, and we extend its targets to RanGAP1 protein. The results …

Complementary Responses To Mean And Variance Modulations In The Perfect Integrate-And-Fire Model, Joanna R. Wares, Todd W. Troyer

Department of Math & Statistics Faculty Publications

In the perfect integrate-and-fire model (PIF), the membrane voltage is proportional to the integral of the input current since the time of the previous spike. It has been shown that the firing rate within a noise free ensemble of PIF neurons responds instantaneously to dynamic changes in the input current, whereas in the presence of white noise, model neurons preferentially pass low frequency modulations of the mean current. Here, we prove that when the input variance is perturbed while holding the mean current constant, the PIF responds preferentially to high frequency modulations. Moreover, the linear filters for mean and variance …

A Glycosylated Recombinant Human Granulocyte Colony Stimulating Factor Produced In A Novel Protein Production System (Avi-014) In Healthy Subjects: A First-In Human, Single Dose, Controlled Study., Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, …

Targeting The Cgmp Pathway To Treat Colorectal Cancer, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This presentation was given in 2009 for the Seminar Series of the Department of Molecular Physiology and Biophysics, Thomas Jefferson University (Philadelphia, PA, USA). It illustrates the role of the calcium-sensing receptor (CaR) and matrix metalloproteinase 9 (MMP-9) as critical downstream mediators of the anticancer GCC pathway in intestine.

Questa presentazione e’ stata effettuata per il Seminar Series del Dipartimento di Fisiologia Molecolare e Biofisica dell’Universita’ del Thomas Jefferson (Filadelfia, USA). La presentazione illustra l’importante ruolo del CaR ed MMP-9 come mediatori della soppressione del processo tumorale dell’intestino da parte del recettore GCC.

Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta

Kimmel Cancer Center Faculty Papers

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is …

Regulation Of Survivin Gene Expression In The Human Endometrium And Endometrial Cancer, Nancy H. Nabilsi

Dissertations and Theses (Open Access)

In the United States, endometrial cancer is the leading cancer of the female reproductive tract. There are 40,100 new cases and 7,470 deaths from endometrial cancer estimated for 2008 (47). The average five year survival rate for endometrial cancer is 84% however, this figure is substantially lower in patients diagnosed with late stage, advanced disease and much higher for patients diagnosed in early stage disease (47). Endometrial cancer (EC) has been associated with several risk factors including obesity, diabetes, hypertension, previously documented occurrence of hereditary non-polyposis colorectal cancer (HNPCC), and heightened exposure to estrogen (25). As of yet, there has …

Human Ribosomal Rna Gene Clusters Are Recombinational Hotspots In Cancer, Dawn Michelle Stults

University of Kentucky Master's Theses

The gene that produces the precursor RNA transcript to the three largest ribosomal RNA molecules (rDNA) is present in multiple copies and organized into gene clusters. They represent 0.5% of the diploid human genome but are critical for cellular viability. The individual genes possess very high levels of sequence identity and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. Our laboratory has developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. In order to determine whether …

Control Of Myosin Motor Activity And Actin Filament Translation By Alteration Of Assay Reducing Potential, Siva Krishna Nalabotu

Theses, Dissertations and Capstones

The use of biomolecular motors for nanotechnological applications has been impaired by an inability to control biomolecular motor activity in a temporal fashion. Previous data has suggested that myosin activity can be modulated by inducing changes in the degree of myosin oxidation. The hypothesis of this study is that myosin motor activity can be regulated by altering the amount of antioxidants and reducing agents present in assay solution. To test this hypothesis we systematically altered the concentration of reducing agents and examined the effects of these changes on myosin-dependent actin filament translation. Our findings indicate that myosin activity can be …

Role Of Oxidative Stress And T Cell Homing In The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jacqueline Perez-Rodriguez

University of Kentucky Doctoral Dissertations

Syngeneic graft-versus-host disease (SGVHD) is induced by reconstituting lethally irradiated mice with syngeneic BM cells followed by a 21 day treatment with the immunosuppressive agent cyclosporine A (CsA). Clinical symptoms of the disease appear 2-3 weeks following cessation of CsA therapy and disease-associated inflammation occurs primarily in the colon and liver.

The development of SGVHD is a complex process resulting from the cooperative interaction of multiple effector cell populations including NK cells, T cells and macrophages. T_H1 cytokines (IL-12, TNF-α, IFN- γ), produced by these effector cells, serve as inflammatory mediators contributing to the pathogenesis of SGVHD. The …

The Association Of Human Leukocyte Antigen(Hla) Alleles And Type 2 Diabetes Mellitus (T2dm) Among Mexican Americans (Ma), Kantibhai Motiram Patel

Open Access Theses & Dissertations

The epidemic of type 2 diabetes mellitus (T2DM) is ranked as a major public health priority across the United States and especially in the El Paso, Texas region. The risk for the development of T2DM is greater in minority groups, particularly among Mexican Americans (MA) who comprise approximately 78% of El Paso's population. The growing incidence of T2DM in this group is typically attributed to increase in weight (obesity). The incidence of diabetes may also be influenced by genetic factors that are unique to this group. Several earlier studies have identified genetic markers for type 1 diabetes mellitus (T1DM). These …

Substrate And Regulation Of Mitochondrial Μ-Calpain, Aashish Joshi

University of Kentucky Doctoral Dissertations

μ -Calpain is localized to the mitochondrial intermembrane space. Apoptosisinducing factor (AIF), which executes caspase-independent cell death, is also localized to the mitochondrial intermembrane space. Following processing at the N-terminus, AIF becomes truncated (tAIF) and is released from mitochondria. The protease responsible for AIF processing has not been established. The same submitochondrial localization of mitochondrial μ-calpain and AIF gives support to the hypothesis that mitochondrial μ-calpain may be responsible for processing AIF. Atractyloside-induced tAIF release in rat liver mitochondria was inhibited by cysteine protease inhibitor MDL28170, but not by calpain inhibitors PD150606 or calpastatin. Moreover, μ-calpain immunoreactivity was difficult to …

Role Of Cyclophilin D In Secondary Spinal Cord And Brain Injury, Jordan Mills Clark

University of Kentucky Doctoral Dissertations

In the hours and days following acute CNS injury, a secondary wave of events is initiated that exacerbate spinal tissue damage and neuronal cell death. A potential mechanism driving these secondary events is opening of the mitochondrial permeability transition pore (mPTP) and subsequent release of several cell death proteins. Previous studies have shown that inhibition of cyclophilin D(CypD), the key regulating component in mPTP opening, was protective against insults that induce necrotic cell death. We therefore hypothesized that CypD-null mice would show improved functional and pathological outcomes following spinal cord injury (SCI) and traumatic brain injury (TBI). Moderate and severe …

Glutamate Regulation In The Hippocampal Trisynaptic Pathway In Aging And Status Epilepticus, Michelle Lee Stephens

University of Kentucky Doctoral Dissertations

A positive correlation exists between increasing age and the incidence of hippocampal-associated dysfunction and disease. Normal L-glutamate neurotransmission is absolutely critical for hippocampal function, while abnormal glutamate neurotransmission has been implicated in many neurodegenerative diseases. Previous studies, overwhelmingly utilizing ex vivo methods, have filled the literature with contradicting reports about hippocampal glutamate regulation during aging. For our studies, enzyme-based ceramic microelectrode arrays (MEA) were used for rapid (2 Hz) measurements of extracellular glutamate in the hippocampal trisynaptic pathway of young (3-6 months), late-middle aged (18 mo.) and aged (24 mo.) urethane-anesthetized Fischer 344 rats. Compared to young animals, glutamate terminals …

Pyramidobacter Piscolens Gen. Nov., Sp. Nov., A Member Of The Phylum ‘Synergistetes’ Isolated From The Human Oral Cavity, Julia Downes, Sonia R. Vartoukian, Floyd E. Dewhirst, Jacques Izard, Tsute Chen, Wen-Han Yu, Iain C. Sutcliffe, William G. Wade

Department of Food Science and Technology: Faculty Publications

Four strains of anaerobic, gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group distinct from any species with validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA–DNA reassociation data revealed that the strains constituted a novel group within the phylum ‘Synergistetes’ and were most closely related to Jonquetella anthropi. Two libraries of randomly cloned DNA were prepared from strain W5455T and were sequenced to provide a genome survey as a resource for metagenomic studies. A new genus …

Cryo-Electron Tomography Elucidates The Molecular Architecture Of Treponema Pallidum, The Syphilis Spirochete, Jacques Izard, Christian Renken, Chyong-Ere Hsieh, Daniel C. Desrosiers, Star Dunham-Ems, Carson La Vake, Linda L. Gebhardt, Ronald J. Limberger, David L. Cox, Michael Marko, Justin D. Radolf

Department of Food Science and Technology: Faculty Publications

Cryo-electron tomography (CET) was used to examine the native cellular organization of Treponema pallidum, the syphilis spirochete. T. pallidum cells appeared to form flat waves, did not contain an outer coat and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. Although the outer membrane (OM) generally was smooth in contour, OM extrusions and blebs frequently were observed, highlighting the structure’s fluidity and lack of attachment to underlying periplasmic constituents. Cytoplasmic filaments converged from their attachment points opposite the basal bodies to form arrays that ran roughly …

Human Ubc9 Contributes To Production Of Fully Infectious Human Immunodeficiency Virus Type 1 Virions, Tareq Jaber, Christopher R. Bohl, Gentry L. Lewis, Charles Wood, John T. West Jr., Robert A. Weldon Jr.

Nebraska Center for Virology: Faculty Publications

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, …

Expression Of Hpv16 E5 Produces Enlarged Nuclei And Polyploidy Through Endoreplication, Lulin Hu, Tamara A. Potapova, Shibo Li, Susannah Rankin, Gary J. Gorbsky, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Anogenital cancers and head and neck cancers are causally-associated with infection by high-risk

human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to

oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can

transform cells when expressed independently. HPV16 E6 and E7 have well-described roles

causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell

transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid

nuclei that are dependent on the level and duration of HPV16 E5 expression. Live-cell imaging

data indicate these changes do not …

Human Papillomavirus 16 E5 Induces Bi-Nucleated Cell Formation By Cell-Cell Fusion, Lulin Ha, Kendra Plafker, Valeriya Vorozhoko, Rosemary E. Zuna, Marie H. Hanigan, Gary J. Gorbsky, Scott M. Plafker, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Human Papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes – E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, …

A Comparative Study Of Hiv-1 Clade C Env Evolution In A Zambian Infant With An Infected Rhesus Macaque During Disease Progression, For Yue Tso, Federico G. Hoffmann, Damien C. Tully, Philippe Lemey, Robert A. Rasmussen, Hong Zhang, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To evaluate whether HIV-1 clade C (HIV-C) envelope variations that arise during disease progression in rhesus macaque model reflect changes that occur naturally in human infection.

Design—An infant macaque was infected with SHIV-1157i, an R5 tropic clade C SHIV (SHIV-C) which expresses a primary HIV-C envelope derived from an infected human infant, and monitored over a five-year period. Genetic variation of the V1-V5 envelope region, which is the main target for humoral immune responses, derived from the infected macaque and infant was examined.

Methods—V1-V5 envelope region were cloned and sequenced from longitudinal PBMC samples collected from the infected macaque and …

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper- dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than …

A Herpesvirus Encoded Deubiquitinase Is A Novel Neuroinvasive Determinant, Joy I. Lee, Patricia J. Sollars, Scott B. Baver, Gary E. Pickard, Mindy Leelawong, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial …

Regulation Of Innate Immune Responses By Bovine Herpesvirus 1 And Infected Cell Protein 0 (Bicp0), Clinton Jones

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single …