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Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi

Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and …

Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation …

The Mucosal Expression Pattern Of Interferon-Ε In Rhesus Macaques, Andrew Demers, Guobin Kang, Fangrui Ma, Wuxun Lu, Zhe Yuan, Yue Li, Mark Lewis, Edmundo N. Kraiselburd, Luis Montaner, Qingsheng Li

Qingsheng Li Publications

Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the …

The Avian Thrombocyte Is A Specialized Immune Cell, Farzana Ferdous

All Dissertations

Thrombocytes are the most abundant circulating cells next to red blood cells in avian blood. Avian thrombocytes are homologous in function to mammalian platelets. Avian thrombocytes and the mammalian platelet are widely recognized contributors to inflammatory responses upon stimulation with various microbial stimulants. However, some observed responses of the avian thrombocyte depart from a standardized model ascribed to innate cells. To help unravel the role of thrombocytes in innate immunity, and possibly adaptive immunity, first we examined the surface features of chicken thrombocytes. Chicken thrombocytes constitutively express transcripts for different Toll-like receptors (TLRs) that are crucial for the innate immune …

Dispositional Optimism: Modeling Cardiovascular Disease Mortality With Traditional Risk Factors And A Psychosocial Personality Trait, Kiana Ramisi Luckett Robinson

Dissertations

Despite increased awareness of clinical risk factors for cardiovascular disease (CVD), heart disease remains a physical and economic burden to African Americans. The aim of this study was to investigate the relationship between dispositional optimism, a psychosocial personality trait, and CVD mortality, based on immediate cause of death. A cross-sectional design was used to examine the predictive value of dispositional optimism in CVD mortality concomitant with traditional CVD risk factors. The traditional CVD risk factors of interest consisted of body mass index, waist circumference, systolic and diastolic blood pressures, total cholesterol, and C-reactive protein. Also, aggregated mortality data for optimists …

Infectious Diseases, Bert Chapman

Libraries Faculty and Staff Scholarship and Research

Provides information about the role of infectious diseases in the early years of U.S. History, with particular emphasis on how they impacted injuries sustained in military conflict.

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

Small-Molecule Probes Targeting The Viral Ppxy-Host Nedd4 Interface Block Egress Of A Broad Range Of Rna Viruses., Ziying Han, Jianhong Lu, Yuliang Liu, Benjamin Davis, Michael S Lee, Mark A Olson, Gordon Ruthel, Bruce D Freedman, Matthias J. Schnell, Jay E Wrobel, Allen B Reitz, Ronald N Harty

Department of Microbiology and Immunology Faculty Papers

Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system, …

A Likelihood Approach To Estimate The Number Of Co-Infections, Kristian A. Schneider, Ananias A. Escalante

Harold W. Manter Laboratory of Parasitology: Library Materials

Article abstract:

The number of co-infections of a pathogen (multiplicity of infection or MOI) is a relevant parameter in epidemiology as it relates to transmission intensity. Notably, such quantities can be built into a metric in the context of disease control and prevention. Having applications to malaria in mind, we develop here a maximum-likelihood (ML) framework to estimate the quantities of interest at low computational and no additional costs to study designs or data collection. We show how the ML estimate for the quantities of interest and corresponding confidence-regions are obtained from multiple genetic loci. Assuming specifically that infections are …

Outcomes Of Third-Year Pharmacy Students Using Technology For Instruction In An Infectious Diseases Elective Course, Joanna Headley, Pharmd, Candidate 2015, Bhavik Shah, Pharmd, Bcps, Aahivp, Jason J. Schafer, Pharmd, Mph, Bcps, Aahivp

College of Pharmacy Faculty Papers

BACKGROUND

• The use of technology both inside and outside the classroom is integral to the facilitation of pharmacy students’ learning.¹

• Technology is allowing education to restructure classroom time for something other than simple transmission of factual information and to adopt an evidence-based approach to instructional innovation and reform.¹

• Pharmacy colleges and schools should incorporate technologies that students frequently use and that positively impact learning.²

• Limited assessment of the impact of technology on student performance is available including teaching and learning from peers.^1,2

• An infectious diseases elective course developed at the Jefferson School of Pharmacy incorporated the …

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Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Application Of Nuclear Magnetic Resonance Based Metabolomics To Study The Central Metabolism Of Staphylococci, Bo Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

Metabolomics studies the collection of small molecules (metabolites) involved in enzymatically catalyzed reactions, cell signaling and cellular structure. Perturbations in metabolite concentrations have been used to reflect the activity of corresponding enzymes or proteins. Nuclear magnetic resonance (NMR) spectroscopy is a well-known approach for the structure determination of biological macromolecules. Alternatively, NMR has recently been established as a valuable tool of metabolomics, in which NMR spectral signals correlate small molecules with cellular activities. This has been accomplished through the chemometric analysis of high-throughput one dimensional ¹H spectra (metabolic fingerprinting) and quantitative metabolite identification based on two dimensional ¹H, …

Identification Of Cd24 As A Cancer Stem Cell Marker In Human Nasopharyngeal Carcinoma, Chun-Hung Yang, Hui-Ling Wang, Yi-Sheng Lin, K. P. Shravan Kumar, Hung-Chi Lin, Chih-Jung Chang, Chia-Chen Lu, Tsung-Teng Huang, Jan Martel, David M. Ojcius, Yu-Sun Chang, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24⁺ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24⁺ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged …

Investigating The Viability Of Two Stenotrophomonas Maltophilia Isolates After Air-Drying, Samantha Lane, Joanna Brooke

DePaul Discoveries

Abstract

Stenotrophomonas maltophilia is a water-borne infectious bacterium that is found in both clinical (hospitals) and non-clinical environments. This human pathogen is commonly recovered from respiratory tract infections. A recent study at a hospital in Taiwan suggested that dry patient charts can serve as a vehicle of transmission of this bacterium⁷. As S. maltophilia is not commonly isolated from dry surfaces, this current study tested the hypothesis that this pathogen can remain viable for some time on a dry surface. This study was designed to determine how long S. maltophilia could remain viable after air-drying by observing …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Genome-Wide Analysis Of Regulatory Proteases Sequences Identified Through Bioinformatics Data Mining In Taenia Solium, Hong-Bin Yan, Zhong-Zi Lou, Li Li, Paul J. Brindley, Yadong Zheng, Xuenong Luo, Junling Hou, Aijiang Guo, Wan-Zhong Jia, Xuepeng Cai

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Cysticercosis remains a major neglected tropical disease of humanity in many regions, especially in sub-Saharan Africa, Central America and elsewhere. Owing to the emerging drug resistance and the inability of current drugs to prevent re-infection, identification of novel vaccines and chemotherapeutic agents against Taenia solium and related helminth pathogens is a public health priority. The T. solium genome and the predicted proteome were reported recently, providing a wealth of information from which new interventional targets might be identified. In order to characterize and classify the entire repertoire of protease-encoding genes of T. solium, which act fundamental biological roles in …

The 24th Annual Research Conference Abstract Booklet, Nikki Lynn Rogers

University of Gondar Research Conferences

Staff members, postgraduate and senior undergraduate students of the University, invited guests and speakers participated in the conference. The annual conference of the University is meant to share experiences in research activities among juniors and seniors, staff and students, and invited guests. It is also meant to motivate students and young faculty to engage in research and also to initiate and strengthen interdisciplinary collaborations. The findings of the studies and the resulting recommendations are expected to be used in solving the diverse societal problems we have been facing.

Research activities at the University of Gondar are primarily aimed at solving …

A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek

Biomedicine and Animal Models in Research Collection

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …

Secretory Iga Is Concentrated In The Outer Layer Of Colonic Mucus Along With Gut Bacteria, Eric W. Rogier, Aubrey L. Frantz, Maria E. C. Bruno, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Antibodies of the secretory IgA (SIgA) class comprise the first line of antigen-specific immune defense, preventing access of commensal and pathogenic microorganisms and their secreted products into the body proper. In addition to preventing infection, SIgA shapes the composition of the gut microbiome. SIgA is transported across intestinal epithelial cells into gut secretions by the polymeric immunoglobulin receptor (pIgR). The epithelial surface is protected by a thick network of mucus, which is composed of a dense, sterile inner layer and a loose outer layer that is colonized by commensal bacteria. Immunofluorescence microscopy of mouse and human colon tissues demonstrated that …

Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley

Publications and Research

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART).

Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients’ medical records.

Results. Plasma HIV RNA …

Implications Of Human Umbilical Cord Blood Cells: An Immunotherapeutic Strategy For Alzheimer's Disease, Donna Darlington

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Alzheimer's disease (AD) is the most common progressive age related dementia and the fourth major cause of mortality in the elderly in the United States. AD is pathologically characterized by deposition of amyloid beta (Aβ) plaques in the brain parenchyma and neurofibrillary tangles (NFTs) within the neuronal soma. While pharmacological targets have been discovered, current strategies for the symptomatic or disease-modifying treatment of AD do not significantly slow or halt the underlying pathological progression of the disease. Consequently, more effective treatment is needed. One possibility for amelioration is using human umbilical cord blood cell (HUCBC) therapy. HUCBCs comprise a …

Urinary Estrogen Metabolites And Self-Reported Infertility In Women Infected With Schistosoma Haematobium, Julio Santos, Maria Joao Gouveia, Nuno Vale, Maria De Lurdes Delgado, Ana Goncalves, Gabriel Rinaldi, Paul J. Brindley, +10 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its …

The Use Of Nanotrap Particles Technology In Capturing Hiv-1 Virions And Viral Proteins From Infected Cells, Elizabeth Jaworski, Mohammed Saifuddin, Gavin C. Sampey, Nazly Shafagati, Rachel Van Duyne, Sergey N. Iordanskiy, Kylene Kehn-Hall, Lance Liotta, Emanuel F. Petricoin Iii, Mary Young, Benjamin Lepene

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV-1 infection results in a chronic but incurable illness since long-term HAART can keep the virus to an undetectable level. However, discontinuation of therapy rapidly increases viral burden. Moreover, patients under HAART frequently develop various metabolic disorders and HIV-associated neuronal disease. Today, the main challenge of HIV-1 research is the elimination of the residual virus in infected individuals. The current HIV-1 diagnostics are largely comprised of serological and nucleic acid based technologies. Our goal is to integrate the nanotrap technology into a standard research tool that will allow sensitive detection of HIV-1 infection. This study demonstrates that majority of HIV-1 …

Household Reporting Of Childhood Respiratory Health And Air Pollution In Rural Alaska Native Communities, Desirae N. Ware, Johnnye Lewis, Scarlett Hopkins, Bert Boyer, Luke Montrose, Curis W. Noonan, Erin O. Semmens, Tony J. Ward

Biomedical and Pharmaceutical Sciences Faculty Publications

Background. Air pollution is an important contributor to respiratory disease in children.

Objective. To examine associations between household reporting of childhood respiratory conditions and household characteristics related to air pollution in Alaska Native communities.

Design. In-home surveys were administered in 2 rural regions of Alaska. The 12-month prevalence of respiratory conditions was summarized by region and age. Odds ratios (ORs) were calculated to describe associations between respiratory health and household and air quality characteristics.

Results. Household-reported respiratory health data were collected for 561 children in 328 households. In 1 region, 33.6% of children aged/or bronchitis. Children with these conditions …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Characterization Of T-Bet And Eomes In Peripheral Human Immune Cells., James J. Knox, Gabriela L. Cosma, Michael R. Betts, Laura M. Mclane

Department of Microbiology and Immunology Faculty Papers

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) …