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 …

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 …

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 …

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 …

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 …

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 …

Bactericidal Effects Of Cold Plasma Technology On Geobacillus Stearothermophilus And Bacillus Cereus Microorganisms, Angela D. Morris, Gayle B. Mccombs, Susan L. Tolle, Mounir Laroussi, Wayne L. Hynes

Dental Hygiene Faculty Publications

Cold plasma is a state of matter that contains a large number of particles that are electrically charged. Plasmas generate chemically reactive species and ultraviolet radiation making them useful in decontamination applications (Kong & Laroussi, 2003). Research regarding the inactivation of gram-positive bacteria by cold plasma has been studied by Laroussi et al (2003); however, there is limited research regarding the germicidal effectiveness of cold plasma on Geobacillus stearothermophilus and Bacillus cereus microorganisms. The purpose of this study was to determine if cold plasma technology inactivates Geobacillus stearothermophilus and Bacillus cereus vegetative cells and spores. This study consisted of 981 …

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …

Ua12/2/1 College Heights Herald, Vol. 83, No. 5, Wku Student Affairs

WKU Archives Records

WKU campus newspaper reporting campus, athletic and Bowling Green, Kentucky news.

Benign Proliferative Epithelial Disorders Of The Breast: A Review Of The Epidemiologic Evidence, Stephanie A. Navarro Silvera, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies …

Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs by elongation factor Tu (EF-Tu) and the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but is able to correct the mistake using a proofreading activity named editing. Previously we found that overproduction of editing-defective PheRS resulted in Tyr incorporation at Phe-encoded positions in vivo , although the misreading efficiency could not be estimated. This raised the question as to whether or not EF-Tu and the ribosome provide further proofreading mechanisms to prevent mistranslation of Phe codons by Tyr. Here we show that, …

Nutritional Composition Of Red Meat, P. G. Williams

Faculty of Health and Behavioural Sciences - Papers (Archive)

Lean red meats are: • An excellent source of high biological value protein, vitamin B12, niacin, vitamin B6, iron, zinc and phosphorus • A source of long-chain omega-3 polyunsaturated fats, riboflavin, pantothenic acid, selenium and possibly also vitamin D • Mostly low in fat and sodium • Sources of a range of endogenous antioxidants and other bioactive substances including taurine, carnitine, carnosine, ubiquinone, glutathione and creatine.

Lead-Contaminated Candies In Southern Nevada, Shawn Gerstenberger, Glenn Savage, Clayton Sellers, Keith Zupnik, Emmanuel C. Gorospe

Environmental & Occupational Health Faculty Publications

Lead-contaminated candies from Latin America are beginning to gain attention in the public media1,2 and in the medical literature.3–5 These candies come from a number of sources and are manufactured outside Food and Drug Administration regulatory control. In 2005, we sampled 50 imported Latin American candies sold in Southern Nevada. A total of 20 (40%) tested positive with an average lead content of 1.46  0.27 mg/kg in the candies’ wrappers and straws, based on standard Graphite Furnace Atomic Absorption Spectrophotometry methodology. Given these results, the Southern Nevada Health District issued a cease-and-desist order on February 13, 2006, to local …