Medical Sciences Commons^™

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Maria Cekanova MS, RNDr, PhD

No abstract provided.

Methods And Compositions For Vaccnation Of Animals With Prrsv Antigens With Improved Immunogenicity, Israrul H. Ansari, Fernando A. Osorio, Asit K. Pattnaik,

School of Veterinary and Biomedical Sciences: Faculty Publications

Pigs challenged with hypoglycosylated variants of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) major surface protein GP5 exhibited increased production of PRRSV-neutralizing antibodies relative to the levels of neutralizing antibodies produced by pigs immunized with wild type (wt) or glycosylated GP5. This invention provides for methods of obtaining improved immune responses in pigs to PRRSV, compositions useful for obtaining the improved immune responses as well as isolated polynucleotides that encode hypoglycosylated variants of PRRSV major surface protein GP5.

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 helperdependent 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 in …

The Elucidation Of Metabolic Pathways And Their Improvements Using Stable Optimization Of Large-Scale Kinetic Models Of Cellular Systems, Evgeni V. Nikolaev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Metabolic engineering of cellular systems to maximize reaction fluxes or metabolite concentrations still presents a significant challenge by encountering unpredictable instabilities that can be caused by simultaneous or consecutive enhancements of many reaction steps. It can therefore be important to select carefully small subsets of key enzymes for their subsequent stable modification compatible with cell physiology. To address this important problem, we introduce a general mixed integer non-linear problem (MINLP) formulation to compute automatically which enzyme levels should be modulated and which enzyme regulatory structures should be altered to achieve the given optimization goal using non-linear kinetic models of relevant …

Role Of Cd4+Cd25+ Regulatory T Lymphocytes In Experimental Toxoplasmosis, Sanjay Varikuti

Masters Theses & Specialist Projects

Toxoplasmosis is an important cause of congenital disease, and it is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome. The need for a reliable experimental model of this infection is crucial not only for achieving a better understanding of the patho-physiology of the disease, but also for developing better methods for evaluating new therapeutic regimens. The purpose of the present study was to investigate the role of CD4+CD25+ T regulatory lymphocytes in mice infected with Toxoplasma gondii. T regulatory (Treg) cells have been shown to play an important role in our immune system in …

E-Science @ Umass: Anticipating And Supporting E-Science Activities At The University Of Massachusetts, Maxine G. Schmidt, Rebecca Reznik-Zellen

Maxine G Schmidt

In March of 2008 an Ad Hoccommittee of Science Librarians from the University of Massachusetts Five Campus System convened to discuss the challenges of e-science and prepare the Libraries for their role in e-science initiatives. Three primary outcomes intended to support e-science activities emerged from the work of the Ad Hoc committee.

The Effect Of Endothelin-1 On The Expression Of Cdk Inhibitors P21 & P27 In Bovine Corneal Endothelial Cells, Lakshmi Reddy Bollu

Masters Theses & Specialist Projects

Mammalian corneal endothelial cells are considered to be non-proliferative due to the arrest of cells at the G1 phase of the cell cycle. The purpose of this study was to determine whether the down regulation of cyclin dependant kinase inhibitors (p21cip1 and p27kip1) levels by Endothelin-1 (ET-1), would overcome the G1 phase arrest and promote cell cycle progression and proliferation in cultured BCECs (Bovine corneal endothelial cells). BCECs were isolated from bovine corneas and cultured in DMEM supplemented with 10% serum. 5-Bromo 2-deoxy Uridine (BrdU) incorporation was determined in serum starved cultures in 24-well plates as a measure of cell …

Single-Amino-Acid Alterations In A Highly Conserved Central Region Of Vesicular Stomatitis Virus N Protein Differentially Affect The Viral Nucleocapsid Template Functions, Debasis Nayak, Debasis Panda, Subash C. Das, Ming Lou, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The nucleocapsid protein (N) of vesicular stomatitis virus and other rhabdoviruses plays a central role in the assembly and template functions of the viral N-RNA complex. The crystal structure of the viral N-RNA complex suggests that the central region of the N protein interacts with the viral RNA. Sequence alignment of rhabdovirus N proteins revealed several highly conserved regions, one of which spanned residues 282 to 291 (GLSSKSPYSS) in the central region of the molecule. Alanine-scanning mutagenesis of this region suggested that replacement of the tyrosine residue at position 289 (Y289) with alanine resulted in an N-RNA template that is …

Effects Of Estrogen On Muscle Damage In Response To An Acute Resistance Exercise Protocol, Megan R. Wolf

Honors Scholar Theses

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid.

Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

E-Science @ The University Of Massachusetts, Maxine G. Schmidt, Rebecca Reznik-Zellen, Raquel Rivera, Cecilia P. Mullen

Maxine G Schmidt

e-Science @ the University of Massachusetts Abstract: What is e-Science and how can libraries and librarians support it? The University of Massachusetts takes a proactive approach to support network-enabled research on its campuses and provides examples where e-Science is already at work. Statement: “e-Science” is a term commonly used to describe research in a networked environment, a growing trend not only in the sciences, but the arts and humanities as well. e-Science creates both opportunities and challenges for academic libraries. The opportunities lie in leveraging the basic skill set that libraries and librarians already possess: the knowledge of and practical …

Biarsenical Labeling Of Vesicular Stomatitis Virus Encoding Tetracysteine-Tagged M Protein Allows Dynamic Imaging Of M Protein And Virus Uncoating In Infected Cells, Subash C. Das, Debasis Panda, Debasis Nayak, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) in place of P and a fusion matrix protein (monomeric red fluorescent protein fused in frame at the carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type (wt) M protein in its normal location, was recovered, but the MmRFP was not incorporated into the virions. Subsequently, we generated recombinant viruses (VSV-PeGFP-∆M-Mtc and VSV-∆M-Mtc) encoding Mprotein with a carboxy-terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant viruses incorporated Mtc at levels similar to M in …

Naloxone's Pentapeptide Binding Site On Filamin A Blocks Mu Opioid Receptor–Gs Coupling And Creb Activation Of Acute Morphine, Hoau-Yan Wang, Lindsay H. Burns

Publications and Research

Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Gαs and its Gβγ dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 µM …

Light-Induced Fos Expression In Intrinsically Photosensitive Retinal Ganglion Cells In Melanopsin Knockout (Opn4-/-) Mice, Gary E. Pickard, Scott B. Baver, Malcolm D. Ogilvie, Patricia J. Sollars

School of Veterinary and Biomedical Sciences: Faculty Publications

Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the …

Use Of Average Mutual Information For Studying Changes In Hiv Populations, Khalid Sayood, Federico Hoffman, Charles Wood

Nebraska Center for Virology: Faculty Publications

Average mutual information (AMI) has been used in a number of applications in bioinformatics. In this paper we present its use to study genetic changes in populations; in particular populations of HIV viruses. Disease progression of HIV-1 infection in infants can be rapid resulting in death within the the first year, or slow, allowing the infant to survive beyond the first year. We study the development of rapid and slow progressing HIV population using AMI charts based on average mutual information among amino acids in the env gene from a population of 1142 clones derived from seven infants with slow …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …

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 …

Umass Libraries 2009, Maxine G. Schmidt

Maxine G Schmidt

No abstract provided.

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

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, …

Spontaneous Idiopathic Arteritis Of The Testicular Artery In Raccoons (Procyon Lotor), A. N. Hamir, M. V. Palmer, H. Li, J. Stasko, D. G. Rogers

School of Veterinary and Biomedical Sciences: Faculty Publications

The testes and the spermatic cord of raccoons (Procyon lotor, kits to adult breeders; n = 48) were examined. Segmental arteritis confined to the extratesticular portions of the testicular artery was present in raccoons of all ages. The arterial changes were seen in laboratory-confined experimental and control animals as well as in wild-caught raccoons. The lesions consisted of proliferative endarteritis with presence of inflammatory cells within the intima, media, and the adventitial regions of most affected vessels. Some aspects of the proliferative arterial lesions were reminiscent of systemic necrotizing vasculitis (polyarteritis nodosa), an immunologically mediated condition of animals and humans. …

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 …

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 …

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 …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …