Medicine and Health Sciences Commons^™

Oral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Buchl, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Direct Inhibition Of Cdk9 Blocks Hiv-1 Replication Without Preventing T Cell Activation In Primary Human Peripheral Blood Lymphocytes, Dominic Salerno, Muneer G Hasham, Renée Marshall Demarest, Judit Garriga, Alexander Y Tsygankov, Xavier Graña

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in transformed cells is very sensitive to direct CDK9 inhibition. Thus, CDK9 could be a potential target for anti-HIV-1 therapy. A clearer understanding of the requirements for CDK9 activity in primary human T cells is needed to assess whether the CDK9-dependent step in HIV-1 transcription can be targeted clinically. We have investigated the effects …

N-Glycan Modification In Aspergillus Species, Elke Kainz, Andreas Gallmetzer, Christian Hatzl, Juergen H. Nett, Huijuan Li, Thorsten Schinko, Robert Pachlinger, Harald Berger, Yazmid Reyes-Dominguez, Andreas Bernreiter, Tillmann Gerngross, Stefan Wildt, Joseph Strauss

Dartmouth Scholarship

The production by filamentous fungi of therapeutic glycoproteins intended for use in mammals is held back by the inherent difference in protein N-glycosylation and by the inability of the fungal cell to modify proteins with mammalian glycosylation structures. Here, we report protein N-glycan engineering in two Aspergillus species. We functionally expressed in the fungal hosts heterologous chimeric fusion proteins containing different localization peptides and catalytic domains. . This strategy allowed the isolation of a strain with a functional -1,2-mannosidase producing increased amounts of N-glycans of the Man 5 GlcNAc 2 type. This strain was further engineered by the introduction of …

Intake Of Coffee And Tea And Risk Of Ovarian Cancer: A Prospective Cohort Study, Stephanie A. Navarro Silvera, Meera Jain, Geoffrey R. Howe, Anthony B. Miller, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

There is some evidence from case-control studies that coffee consumption might be positively associated with ovarian cancer risk, whereas the epidemiologic evidence regarding tea consumption and ovarian cancer is inconsistent. To date, there have been few prospective studies of these associations. Therefore, we examined ovarian cancer risk in association with both coffee and tea intake in a prospective cohort study of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending …

Light-Evoked Calcium Responses Of Isolated Melanopsin- Expressing Retinal Ganglion Cells, Andrew T. E. Hartwick, Jayne R. Bramley, Jianing Yu, Kelly T. Stevens, Charles N. Allen, William H. Baldridge, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ( [Ca²⁺]_i ) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input. Light induced a rise in [Ca²⁺]_i (monitored using fura-2 imaging) in the immunopanned ipRGCs and the source of this Ca²⁺ signal was investigated. The Ca²⁺ responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1–2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic acid, …

A Quantitative Synthesis Of The Medicinal Ethnobotany Of The Malinké Of Mali And The Asháninka Of Peru, With A New Theoretical Framework, Nathaniel Bletter

Publications and Research

Background: Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.

Methods: A new quantitative theoretical framework of mathematical …

Feline Lentivirus: Molecular Analysis And Epidemiology In Southern African Lions, Hayley Rebecca Adams

Doctoral Dissertations

Feline immunodeficiency virus is a retrovirus of domestic cats causing significant lifelong infection. Infection has also been detected in nondomestic species, including African lions. It is endemic in certain populations in east and southern Africa. Infection leads to immunologic dysfunction and immunosuppressive disease in domestic cats; however, little research exists about the pathogenic effects of infection in lions and its epidemiological impact on free-ranging and captive populations. Little is known about the lentivirus in these populations at the molecular and host level. Analysis of the virus from these populations is necessary for development of detection assays that are both sensitive …

Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng

Microbiology Publications and Other Works

Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag-specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to the intranasal route of …

Statistical Issues In Proteomic Research, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.

Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng

Thandi M. Onami

Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag-specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to the intranasal route of …

Glucose-6-Phosphate Dehydrogenase (G6pd) Screening In Pakistani Neonates: To Be Or Not To Be, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Low Back Pain Among College Athletes - A Survey Of Basketball Players, Swimmers, Track And Field Athletes And Nonathletic Controls, Nicholas Bacon

Masters Theses & Specialist Projects

Study Design. Cross-sectional survey among athletes competing at the collegiate level in basketball, swimming, and track and field, as well as a matched nonathletic control group. Objective. To compare the prevalence of low back pain between sports: basketball, swimming, and track and field, as well as nonathletic control group. Summary of Background Data. With conflicting reports, it is not clear whether athletes are at higher risk for low back pain when compared to nonathletic counterparts. Some literature has found that low back pain was less common in former elite athletes when compared to nonathletes; however, much of the literature supports …

The Environmental Factors Regulating The Distribution Of Crayfish In The Upper Green River Basin Kentucky, Usa, Eva Ngulo

Masters Theses & Specialist Projects

Despite the importance of crayfish in aquatic systems there are major issues threatening their conservation, including invasive species, habitat alterations, and species with small distributions or have limited geographical ranges. There is limited information regarding native range, habitat requirements, life histories and biological interactions between crayfish species. In order to examine the relationship between lotic crayfish assemblages and environmental variables at both the watershed and reach scales, data were collected from 46 stream segments in the Upper Green River Basin of Kentucky, U.S.A. An independent sample t-test compared crayfish densities between segments with gravel - small cobble, and large cobble …

Longitudinal Tracking Of Cytokines After Acute Exposure To Tuberculosis: Association Of Distinct Cytokine Patterns With Protection And Disease Development, Rabia Hussain, Najeeha Talat, Firdaus Shahid, Ghaffar Dawood

Department of Pathology and Laboratory Medicine

Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-gamma] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 …

Conferred Immunity Against The H1n1 Type A Influenza Virus In Madin-Darby Canine Kidney Cells Via Cecropin B Transfection Therapy., Tomasz P. Stryjewski

Honors Theses

No abstract provided.

Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman

Natural Sciences and Mathematics | Faculty Scholarship

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors …

Leptospira Interrogans Endostatin-Like Outer Membrane Proteins Bind Host Fibronectin, Laminin And Regulators Of Complement, Brian Stevenson, Henry A. Choy, Marija Pinne, Matthew L. Rotondi, M. Clarke Miller, Edward Demoll, Peter Kraiczy, Anne E. Cooley, Trevor P. Creamer, Marc A. Suchard, Catherine A. Brissette, Ashutosh Verma, David A. Haake

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF …

Xml Encoding Of Features Describing Rule-Based Modeling Of Reaction Networks With Multi-Component Molecular Complexes, Michael L. Blinov, Ion I. Moraru

UCHC Articles - Research

Multi-state molecules and multi-component complexes are commonly involved in cellular signaling. Accounting for molecules that have multiple potential states, such as a protein that may be phosphorylated on multiple residues, and molecules that combine to form heterogeneous complexes located among multiple compartments, generates an effect of combinatorial complexity. Models involving relatively few signaling molecules can include thousands of distinct chemical species. Several software tools (StochSim, BioNetGen) are already available to deal with combinatorial complexity. Such tools need information standards if models are to be shared, jointly evaluated and developed. Here we discuss XML conventions that can be adopted for modeling …

2007 Scholars And Artists Bibliography, Michael Schwartz Library, Cleveland State University, Friends Of The Michael Schwartz Library, Joanne E. Goodell Ph.D.

Scholars and Artists Bibliographies

This bibliography was created for the annual Friends of the Michael Schwartz Library Scholars and Artists Reception, recognizing scholarly and creative achievements of Cleveland State University faculty, staff and emeriti. Dr. Joanne Goodell was the guest speaker.

Considerations For Determining Optimal Mouse Caging Density, Charmaine Foltz, Larry Carbone, David Delong, Bernard E. Rollin, Pascalle Van Loo, Julia Whitaker, Axel Wolff

Laboratory Research and Animal Welfare Collection

At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal well-being should be the measure of interest in evaluating housing density and that well-being includes not …

Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm

Erika A. Taylor, Ph.D.

The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for …

The Potential Role Of Probiotics In Reducing Poverty-Associated Infections In Developing Countries, Kingsley C. Anukam

Kingsley C Anukam

Probiotics are defined by the Food and Agricultural Organization/ World Health Organization as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” [1]. The potential benefits of their use have not been adequately investigated, especially in the developing world. Japan introduced Yakult, a probiotic fermented food drink in 1935, and in the Northern hemisphere, research and use of probiotics has gained an unprecedented momentum in the last decade [2]. Use of probiotics is not uncommon in Europe [3], but in many developing countries use of probiotics in its present definition is a foreign concept. …

Site-Directed Mutations In The C-Terminal Extension Of Human Αb-Crystallin Affect Chaperone Function And Block Amyloid Fibril Formation, T. M. Treweek, Heath Ecroyd, D. M. Williams, S. Meehan, J. A. Carver, M. J. Walker

Faculty of Health and Behavioural Sciences - Papers (Archive)

Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αBcrystallin, play a role in the prevention of protein deposition. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of αB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal …

Evaluating Forensic Dna Evidence - A Day-Long Workshop, Dan E. Krane, William C. Thompson

Biological Sciences Faculty Publications

No abstract provided.

Enhancement Of Efficacy Of Prrsv Vaccines By Altering The Glycosylation Pattern Of Viral Glycoproteins, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

PRRSV, the causative agent of PRRS is of major economic significance to the pork industry in the USA and around the world. Current commercial vaccine does not provide adequate protection against PRRSV outbreaks. Therefore, there is an urgent need for development of more efficacious vaccine to combat PRRS. Our previous studies have suggested that (i) induction of neutralizing antibody response is an important correlate of evaluating the efficacy of a vaccine; (ii) neutralizing antibodies can be enhanced by hypoglycosylation of the major surface glycoprotein (GP5). While it is known that GP5 plays a prominent role in neutralizing antibody induction, it …

Characterization Of Mazfsa, An Endoribonuclease From Staphylococcus Aureus, Zhibiao Fu, Niles P. Donegan, Guido Memmi, Ambrose L. Cheung

Dartmouth Scholarship

The mazEF homologs of Staphylococcus aureus, designated mazEF(sa), have been shown to cotranscribe with the sigB operon under stress conditions. In this study, we showed that MazEF(Sa), as with their Escherichia coli counterparts, compose a toxin-antitoxin module wherein MazF(Sa) leads to rapid cell growth arrest and loss in viable CFU upon overexpression. MazF(Sa) is a novel sequence-specific endoribonuclease which cleaves mRNA to inhibit protein synthesis. Using ctpA mRNA as the model substrate both in vitro and in vivo, we demonstrated that MazF(Sa) cleaves single-strand RNA preferentially at the 5' side of the first U or 3' side of the second …

Glycaemic Index, Glycaemic Load And Ovarian Cancer Risk: A Prospective Cohort, Stephanie A. Navarro Silvera, Meera Jain, Geoffrey R. Howe, Anthony B. Miller, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

Background

There is some evidence that plasma insulin levels might influence ovarian cancer risk. Glyacemic index (GI) and glycaemic load (GL) are measures that allow the carbohydrate content of individual foods to be classified according to their postprandial glycaemic effects and hence their effects on circulating insulin levels. Therefore, we examined ovarian cancer risk in association with GI and GL, and intake of dietary carbohydrate and sugar. Methods

The study was conducted in a prospective cohort of 49 613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food-frequency questionnaire (FFQ) between 1980 and 1985. …

Glycaemic Index, Glycaemic Load And Ovarian Cancer Risk: A Prospective Cohort Study, Stephanie A. Navarro Silvera, Meera Jain, Geoffrey R. Howe, Anthony B. Miller, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

Background

There is some evidence that plasma insulin levels might influence ovarian cancer risk. The glycaemic index (GI) and glycaemic load (GL) are measures that allow the carbohydrate content of individual foods to be classified according to their postprandial glycaemic effects and hence their effects on circulating insulin levels. Therefore, we examined ovarian cancer risk in association with GI and GL, and intake of dietary carbohydrate and sugar.

Methods

The study was conducted in a prospective cohort of 49 613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food-frequency questionnaire (FFQ) between 1980 and …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Experimentation Collection

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

Santa Clara Magazine, Volume 49 Number 2, Fall 2007, Santa Clara University

Santa Clara Magazine

14 - A DAY IN THE LIFE OF THE PRESIDENT By Ron Hansen. Set your alarm clock early-then get up and follow Paul Locatelli, S.J., through a day of leading the University and serving as pastor, professor, mayor, and CEO.

22 - BUILT BY IMMIGRANTS By Gerald McKevitt, S.J. How Italian Jesuits helped shape the American West, from religious devotions to curriculum to pasta.

28 - YOU ARE HERE By Sarah Stanek. SCU students and faculty collaborate on a groundbreaking project documenting early life at Mission Santa Clara-and the result is a book that's the first of its kind for …