Digital Commons Network^™

Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, crossprotective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated …

Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir + tenofovir alafenamide + emtricitabine; EVG + TAF + FTC) drugs (mimicking marketed Genvoy® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored …

Characterization Of The Ecological Role Of Genes Mediating Acid Resistance In Lactobacillus Reuteri During Colonization Of The Gastrointestinal Tract, Janina A. Krumbeck, Nathan L Marsteller, Steven Frese, Daniel A. Peterson, Amanda Ramer-Tait, Robert W. Hutkins, Jens Walter

Department of Food Science and Technology: Faculty Publications

Rodent-derived strains of Lactobacillus reuteri densely colonize the forestomach of mice and possess several genes whose predicted functions constitute adaptations towards an acidic environment. The objective of this study was to systematically determine which genes of L. reuteri 100-23 contribute to tolerance towards host gastric acid secretion. Genes predicted to be involved in acid resistance were inactivated, and their contribution to survival under acidic conditions was confirmed in model gastric juice. Fitness of five mutants that showed impaired in vitro acid resistance were then compared through competition experiments in ex-germ-free mice that were either treated with omeprazole, a proton-pump inhibitor …

Exploratory Study Of Seasonal Indoor Bioaerosols And The Associated Health Outcomes In Low-Income Communities In El Paso, Texas, 2014, Eric Martinez

Open Access Theses & Dissertations

Introduction: Structural degradation, moisture levels, and building failures can influence poor indoor air quality and create a good environment for bioaerosols. People spend much of their time indoors and can potentially be exposed to these bioaerosols. Several studies have correlated exposures to high concentrations of bioaerosols to various health problems, severe allergies, asthma, or other respiratory illness. Objectives: The objectives of this study are to describe bioaerosol concentrations, meteorological factors, and health outcomes during the summer and fall seasons; characterize bioaerosols (bacteria and fungi) collected in low-income communities; compare bioaerosol concentrations by season; compare meteorological factors to bioaerosol concentrations by …

The Effects Of Stress And Alcohol On Hiv-1 Latency, Sarah Ilene Talley

Master's Theses

A major barrier to HIV eradication is the persistence of latent viral reservoirs that exist despite antiretroviral therapy. In order to develop effective therapeutics, a comprehensive understanding of latency and factors driving the formation of the latent reservoir is needed. As stress and alcohol are common comorbidities associated with HIV infection, the goal of this research was to determine how stress and alcohol could affect HIV-latency. Specifically, we hypothesized that the ability of latent proviruses to be reactivated by “shock and kill” approaches would be altered by glucocorticoid and ethanol treatments, and prolonged ethanol exposure would affect the size of …

Characterization Of Oral Microbiota In Xerostomic Versus Non-Xerostomic Volunteers And In Daily Samples Following Standard Oral Hygiene Practices, Chelsea Myers

Wayne State University Theses

A thesis presented on the characterization of oral microbiota in xerostomic versus non-xerostomic volunteers and in daily samples following standard oral hygiene practices. Xerostomia is a difficult and burdensome disease that can be very difficult to diagnose. Understanding the oral microbiota between these diseased and healthy (non-xerostomic) can give us great insight on new treatments and/or prevention. Goals of the study included determining whether there substantial differences in oral microbial populations between the two groups, and whether varying nightly oral hygiene practices had an impact on next-morning oral microbiota titers or composition. Microbial loads were determined by qPCR using broad-spectrum …

Characterization Of Transfer Of The Mobile Genomic Island Encoding Methicillin Resistance Among Staphylococci, Melissa D. Ray

Theses and Dissertations

The gene encoding methicillin resistance in Staphylococcus aureus (MRSA) is carried in the chromosome on a large genomic island called SCCmec and is always inserted at the att site within orfX. SCCmec has been designated a mobile genetic element but a mechanism by which it moves among different strains and species of staphylococci has never been demonstrated. This work shows that bacteriophage 80α is capable of transducing SCCmec into a recipient cell, after which it can integrate into the bacterial chromosome via homologous recombination. More importantly, this work characterizes a conjugative mechanism of SCCmec transfer. …

Orientia Tsutsugamushi Ankyrin-Repeat Protein Family Targeting Of The Host Endoplasmic Reticulum, Lauren Viebrock

Theses and Dissertations

Abstract

ORIENTIA TSUTSUGAMUSHI ANKYRIN REPEAT-PROTEIN FAMILY TARGETING OF THE HOST ENDOPLASMIC RETICULUM

By Lauren VieBrock, B.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2015

Director: Jason A. Carlyon, Ph.D.

Professor

Microbiology and Immunology

Scrub typhus is an understudied, potentially fatal febrile illness, which poses threat to one billion people annually in the Asia-Pacific region. The host-pathogen interactions that facilitate the intracellular survival of the etiologic agent, Orientia tsutsugamushi, are not well understood. The Orientia tsutsugamushi genome encodes a large number of ankyrin repeat-containing proteins …

Development Of Novel Chimeric Epitope Based Diagnostic Antigens And Vaccines For Lyme Disease, Lee D. Oliver Jr.

Theses and Dissertations

Lyme disease (LD) is the leading arthropod-borne disease in North America with 300-600,000 cases each year. There are currently no approved human LD vaccines. Outer surface protein C (OspC) has emerged as a leading vaccine candidate and an attractive diagnostic marker due to its antigenicity and expression early in infection. Several chimeric, epitope based OspC derived proteins were generated. The constructs were found to be highly immunogenic in mice and vaccination induced complement-dependent bactericidal antibodies. These results suggest that a broadly protective polyvalent OspC epitope based vaccine can be produced. Currently, LD diagnostic approaches are unreliable and unable to differentiate …

Correlation Analysis Of Climatic Variables, Migration And Dengue Cases In Southeast Florida, Brunilda Lugo

Walden Dissertations and Doctoral Studies

Dengue fever is a debilitating, viral, mosquito-borne disease occurring in tropical and subtropical areas in the world. The majority of dengue cases in the United States were acquired in endemic areas by travelers or immigrants. However, in recent years, autochthonous (locally acquired) dengue cases have been diagnosed in Florida. The purpose of this study was to find an association between potential risk factors and the expansion of dengue fever in the United States. Guided by the eco-bio-social framework, which offers a broad assessment of risk factors for the illness, a retrospective design was used with archival data to correlate changes …

Exploring The Role Of Intracellular Aminopeptidases In Staphylococcus Aureus Pathogenesis, Devon Nicole Marking

USF Tampa Graduate Theses and Dissertations

Staphylococcus aureus is a remarkably pathogenic bacterium that is widely prevalent among the human population. It is the leading agent of skin and soft tissue infections, and is also responsible for causing an array of severe and life threatening diseases. The invasiveness of the pathogen, coupled with increasing antibiotic resistance seen for S. aureus infections, makes this bacterium a prominent public health concern. The extended pathogenicity of S. aureus is largely due to its repertoire of virulence factors, which are typically characterized by being bound to the cell wall, or secreted into the extracellular environment. Previously, our lab identified a …

Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood

Dartmouth Scholarship

Viral infection results in the generation of massive numbers of activated effector CD8+ T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing …

Characterization Of Salmonella Enterica Isolates From Food And Clinical Samples: Functionality Of Cytolethal Distending Toxin (Cdt) From Non-Typhi Salmonella Enterica, Ezat Hussain Mezal

Theses and Dissertations

Salmonella enterica is recognized worldwide as a significant cause of both human and animal disease. Recently, many random outbreaks of infections associated with the pathogens have been documented. Thus, state of the art molecular tools are necessary to conduct effective surveillance that would aid monitoring and prevention of disease. In this study, 110 Salmonella enterica serovars (Enteritidis & Javiana) strains isolated from food, environmental and clinical samples were analyzed for genetic diversity, antibiotic resistance, presence of virulence genes, plasmids, and plasmid replicon types. To assess the genetic diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting, multiple-locus variable-number tandem repeat analysis (MLVA) and …

In The Social Amoeba, Dictyostelium Discoideum , Density, Not Farming Status, Determines Predatory Success On Unpalatable Escherichia Coli, Susanne Disalvo, Debra A. Brock, Jeff Smith, David C. Queller, Joan E. Strassmann

Biology Faculty Research

Background
The social amoeba Dictyostelium discoideum interacts with bacteria in a variety of ways. It is a predator of bacteria, can be infected or harmed by bacteria, and can form symbiotic associations with bacteria. Some clones of D. discoideum function as primitive farmers because they carry bacteria through the normally sterile D. discoideum social stage, then release them after dispersal so the bacteria can proliferate and be harvested. Some farmer-associated bacteria produce small molecules that promote host farmer growth but inhibit the growth of non-farmer competitors. To test whether the farmers’ tolerance is specific or extends to other growth inhibitory …

Antibacterial Activity Of Commercially Available Plant Extracts On Selected Campylobacter Jejuni Strains, Divya Oppath Sivasankaran

Graduate Theses and Dissertations

Campylobacter jejuni is recognized as a leading cause of foodborne illness worldwide with approximately 850,000 cases per year in the United Sates. A total of 18 species of Campylobacter have been identified worldwide to date. Foodborne transmission of C. jejuni is mainly through the consumption of unpasteurized milk, contaminated poultry meat and water. C. jejuni can survive in very diverse environments under stressful conditions in human and animals which is different from the specific conditions and media required in laboratory experiments. There has been increased research in recent years to identify naturally occurring antibacterial agents to control and eliminate C. …

Quantitative Analysis And Imaging-Based Insights Into The Characteristics And Mechanisms Of Yeast Pattern Formation, Lin Chen

Dissertations and Theses (Open Access)

Biofilm formation is a common lifestyle adapted by bacteria and fungi in response to various environmental stresses. Bacterial and fungal biofilms adhering to medical devices convey resistance to antibiotics or biocides, causing high rates of clinical infections. Microorganisms are protected from harsh environmental conditions by reduced stress penetration through the complex biofilm architecture with distinct patterns. Although the molecular regulations of surface patterning have been well characterized in bacteria, the mechanisms underlying the complex pattern formation in eukaryotic biofilms remain unclear.

This dissertation aims to investigate the salient features of robust colony expansion in yeast biofilms and the processes driving …

Enhancement Of Antimicrobial Activity Of Naturally Occuring Phenolic Compounds By Nano-Particle Mediated Delivery Against Listeria Monocytogenes, Escherichia Coli O157:H7, And Salmonella Typhimurium, Madhuram Ravichandran

Graduate Theses and Dissertations

Food-borne illnesses are of major concern in the U.S. and worldwide. Salmonella,Listeria,E. coli O157:H7 continue to be some of the major foodborne pathogens. Recurring recalls due to these pathogens demand critical antimicrobial strategies to decontaminate the food through its procession from farm to fork. In our study, we combined the effectiveness of naturally occurring phenolic compounds individually, with/ without ethylenediamine tetraacetic acid (EDTA) and/or Nisin and nanoparticle delivery to improve the antimicrobial potential of the compounds against Listeria monocytogenes (L.m.), Salmonella Typhimurium (S.T.), and Escherichia coli O157:H7 (E.c.), in brain …

A Portable Impedance Biosensing System Based On A Laptop With Labview For Rapid Detection Of Avian Influenza Virus, Yixiang Wang

Graduate Theses and Dissertations

Avian Influenza Virus (AIV) H5N1 is a highly pathogenic virus found not only in birds but also in human. Rapid and sensitive detection method is needed to help prevent the spread of AIV H5N1. In this study, a portable impedance biosensing system based on a laptop with LabVIEW software was developed for detection of AIV H5N1. First, a virtual instrument was programmed with LabVIEW software to form a platform for impedance measurement, data processing and control. The audio card of a laptop was used as a function generator while a data acquisition card was used with the signal channels for …

Genetic Susceptibility, Colony Size, And Water Temperature Drive White-Pox Disease On The Coral Acropora Palmata, Erinn M. Muller, Robert Van Woesik

Ocean Engineering and Marine Sciences Faculty Publications

Outbreaks of coral diseases are one of the greatest threats to reef corals in the Caribbean, yet the mechanisms that lead to coral diseases are still largely unknown. Here we examined the spatial-temporal dynamics of white-pox disease on Acropora palmata coral colonies of known genotypes. We took a Bayesian approach, using Integrated Nested Laplace Approximation algorithms, to examine which covariates influenced the presence of white-pox disease over seven years. We showed that colony size, genetic susceptibility of the coral host, and high-water temperatures were the primary tested variables that were positively associated with the presence of white-pox disease on A. …

Role Of Type Iv Pili In Predation By Bdellovibrio Bacteriovorus, Ryan M Chanyi, Susan F Koval

Microbiology & Immunology Publications

Bdellovibrio bacteriovorus, as an obligate predator of Gram-negative bacteria, requires contact with the surface of a prey cell in order to initiate the life cycle. After attachment, the predator penetrates the prey cell outer membrane and enters the periplasmic space. Attack phase cells of B. bacteriovorus have polar Type IV pili that are required for predation. In other bacteria, these pili have the ability to extend and retract via the PilT protein. B. bacteriovorus has two pilT genes, pilT1 and pilT2, that have been implicated in the invasion process. Markerless in-frame deletion mutants were constructed in a prey-independent mutant to …

Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu

Open Access Dissertations

Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Fermented Food: Putting The Power Of Good Health Back Into The Hands Of The People, Marsha L. Thadison

Professional Agricultural Workers Journal

Editors’ Note: At the December 2013 Professional Agricultural Workers Conference, several women were invited to share, information about their unique businesses. One such presenter was Marsha L. Thadison, owner of Yesterday’s Kitchen 4 Today, a company that focuses on promoting functional foods. Thadison shared that food is produce and consumed differently from previous generations. Today's food, she argued, involves many more agricultural inputs that aid in food preservation, extension of shelf life, and promotion of animal health. She espoused the benefits of fermented food.

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 …

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

Oroya Fever And Verruga Peruana: Bartonelloses Unique To South America, Michael F. Minnick, Burt E. Anderson, Amorce Lima, James M. Battisti, Phillip G. Lawyer, Richard J. Birtles

Biological Sciences Faculty Publications

Bartonella bacilliformis is the bacterial agent of Carrión's disease and is presumed to be transmitted between humans by phlebotomine sand flies. Carrión's disease is endemic to high-altitude valleys of the South American Andes, and the first reported outbreak (1871) resulted in over 4,000 casualties. Since then, numerous outbreaks have been documented in endemic regions, and over the last two decades, outbreaks have occurred at atypical elevations, strongly suggesting that the area of endemicity is expanding. Approximately 1.7 million South Americans are estimated to be at risk in an area covering roughly 145,000 km2 of Ecuador, Colombia, and Peru. Although disease …

Bartonella Henselae Infection And Host Response In The Zebrafish Embryo Model, Amorce Lima

USF Tampa Graduate Theses and Dissertations

The Gram-negative bacterium Bartonella henselae (Bh) is an emerging zoonotic pathogen that has been associated with a variety of human diseases including bacillary angiomatosis which is characterized by vasoproliferative tumor-like lesions on the skin and internal organs of some immunosuppressed individuals. Several virulence factors associated with Bartonella-induced pathogenesis have been characterized. However, the study of those virulence factors has been limited to in vitro cell culture systems due to the lack of a practical animal model. Therefore, we wanted to investigate whether the zebrafish embryo (Danio rerio) could be used to model human infection with Bh. We investigated …

Effect Of Chemotherapy On The Microbiota And Metabolome Of Human Milk: A Case Report, Camilla Urbaniak, Amy Mcmillan, Michelle Angelini, Gregory B Gloor, Mark Sumarah, Jeremy P Burton, Gregor Reid

Microbiology & Immunology Publications

BACKGROUND: Human milk is an important source of bacteria for the developing infant and has been shown to influence the bacterial composition of the neonatal gut, which in turn can affect disease risk later in life. Human milk is also an important source of nutrients, influencing bacterial composition but also directly affecting the host. While recent studies have emphasized the adverse effects of antibiotic therapy on the infant microbiota, the effects of maternal chemotherapy have not been previously studied. Here we report the effects of drug administration on the microbiota and metabolome of human milk.

METHODS: Mature milk was collected …

Understanding The Factors Affecting Microbiological Quality Of Wheat Milled Products: From Wheat Fields To Milling Operations, Luis E. Sabillón Galeas

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Although regarded as a low-risk commodity, wheat flour-based mixes have been implicated in several food safety incidents. The present thesis is a compilation of five scientific manuscripts on the effect of weather variation, milling steps and implementation of pre-milling interventions on the microbiological quality and safety of wheat and milled products. The first manuscript is a review of the microbiological quality and safety of wheat-based products. Despite the low water activity, wheat flour may harbor dormant but viable microorganisms, which could lead to safety concerns when flour is used to produce refrigerated dough products. The second manuscript illustrates the effect …