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Combating Infectious Diseases In Aquaculture With An Original Probiotic Product, Meagan Hamblin, Saebom Sohn, Christine Ahn Dao, Marta Gomez-Chiarri, David R. Nelson, David Worthen, David Rowley

Senior Honors Projects

Oyster production in Rhode Island accounts for over $2.5 million in annual revenue, making it the top aquaculture product in the state. However, larval tank infections significantly constrain production and create substantial economic losses for commercial hatcheries. In most cases antibiotics may not be used to prevent or treat larval tank infections. A probiotic, or beneficial microbe which competes with pathogens, is a safer and “green” approach to preventing infections. Vibriosis, a common cause of oyster larval mortality, is the result of Vibrio species infections. Previous studies have shown that a native Rhode Island microbe, Bacillus pumilus RI06-95, protects oyster …

The Effects Of Diet And The Microbiome On Reproduction And Longevity: A Comparative Review Across 5 Continents, Stephanie N. Chilton, Megan K. Enos, Jeremy P. Burton, Gregor Reid

Microbiology & Immunology Publications

Human longevity and quality of life remain key societal drivers, but the healthcare burden of diet-related chronic diseases is economically unmanageable. In recent years, it has been proposed that the composition and abundance profiles of certain bacterial phyla in the gut are indicators of malnutrition, and ill health. But, how much does the gut microbiome and diet really contribute to outcomes? The description of three microbial enterotypes remains to be verified, as does its significance for health tested across continents and within people who migrate from one lifestyle to another. It is not simply that the diet of one region …

How Probiotics And The Microbiome Will Change Medical Practice, Gregor Reid

Microbiology & Immunology Publications

No abstract provided.

Characterization Of The Innate Response To The Ragb Protein Of Porphyromonas Gingivalis., Justin Hutcherson

Electronic Theses and Dissertations

More than 64 million people in the US suffer from some form of periodontal disease. Periodontal diseases are bacterial infections of the hard and soft tissues surrounding the teeth which can lead to tooth loss. Periodontal tissue destruction is caused by inflammatory host-pathogen interactions. Porphyromonas gingivalis is a major causative agent of periodontal diseases and is a keystone periodontal pathogen. The 55kDa immunodominant RagB outer membrane protein of P. gingivalis has been proposed to facilitate iron transport. However, potential interactions between RagB and the innate response have not been examined. RagB homologues in gut Bacteroidetes have been associated with inflammatory …

Critical Insights Into The Pathogenesis Of Clinical Isolates Of Pandemic Influenza A(H1n1) 2009 Virus In Mouse And Ferret Models., Jeremy V. Camp 1980-

Electronic Theses and Dissertations

Influenza A virus (IAV) is a minus-sense, segmented, single-stranded RNA virus that infects the respiratory tract of humans and can cause severe illness. Novel IAV variants perpetually emerge on every continent, and the emergence of variants with increased transmissibility and/or pathogenesis in the human population is a serious concern for global public health. Infection with IAV typically causes an acute, self-limiting upper respiratory tract disease. However, severe IAV disease is characterized by infection of the lower respiratory tract which can lead to pneumonia and may result in the development of acute respiratory distress syndrome (ARDS). Viral and host contributions to …

Early Host Response And Immune Signaling To 2009 Pandemic Influenza A (H1n1) Viruses In Primary Cell Culture Models., Rachael Lask Gerlach

Electronic Theses and Dissertations

Influenza A virus (IAV) subtypes and even genotypes within subtypes can show differences in tropism (host, cell type), magnitude of infection, immune response and progression of illness. My dissertation focused on the development and use of two in vitro physiologically-relevant human cell culture models, well-differentiated normal human bronchial epithelial (wdNHBE) cells and human monocyte-derived macrophages (MDM) for the study of early IAV-host interactions. These models have given new insight into early host responses to seasonal H1N1 (BN59) and two pandemic A(H1N1)2009 viruses or H1N1pdm herein. The H1N1pdm are clinical isolates from a fatal (A/KY/180/10) and nonfatal (A/KY/136/09) case. In the …

Identification Of Transcription Factors Gzf3, Rfx1, Orf19.3928 As Being Implicated In Candida-Bacterial Interactions., Joni Watson

Undergraduate Honors Theses

Candida albicans is an opportunistic pathogen that is present in the normal flora in a majority of individuals. One key factor in C. albicans virulence is the ability to change its morphology from yeast to an elongated or hyphal form. The regulation of this morphogenesis relies in part upon quorum sensing (QS) molecules. C. albicans often exists as part of a mixed culture alongside other microbes and is influenced by their presence as well as the presence of QS molecules that they produce. In this study, a library of diploid homozygous transcriptional regulator knockout (TRKO) mutants were screened to identify …

The Uptake And Incorporation Of Exogenous Fatty Acids Confer Phenotypic Advantages To Acinetobacter Baumannii, Saba A. Munir

Honors Theses

AIM: Acinetobacter baumannii is a ubiquitous gram-negative bacterium found on a variety of surfaces that include skin, hair, and soil. Some gram-negative bacteria like A. baumannii have the ability to acquire and incorporate fatty acids into their phospholipid membranes. Known as ‘Iraqibacter,’ A. baumannii has emerged as a significant cause of nosocomial infections in the United States and abroad. This study was designed to determine whether structural alterations occur in A. baumannii upon exposure to a wide range of polyunsaturated fatty acids (PUFAs) as well as the significance of this phenomenon in terms of survival and resistance to stress. Thin …

The Effect Of Activation Induced Cytidine Deaminase Phosphorylation And Herpes Virus Uracil Dna Glycosylase On Antibody Diversification, Marc Macaluso

Dissertations and Theses (Open Access)

Activation-induced cytidine deaminase (AID) is a mutagenic enzyme that is expressed in mammalian B-cells and initiates the antibody diversification processes of somatic hypermuntation (SHM) and isotype class switch recombination (CSR). AID is targeted to the immunoglobulin gene locus where it deaminates cytosines to generate uracil residues in DNA. This generates guanine-uracil (U:G) mismatch lesion which are recognized by uracil DNA glycosylase (UNG), a DNA repair enzyme that removes uracil from DNA and triggers downstream repair of the lesion. While UNG is a ubiquitously expressed DNA repair enzyme, its recognition and removal of AID introduced uracils is essential in both SHM …

Influence Of The Anti-Hiv Drug Elvitegravir On Chlamydial Development And The Characterization Of Chlamydial Polymorphic Membrane Protein Expression In Herpes Simplex Virus (Hsv)/C. Trachomatis Co-Infected Cells, Hena Yakoob

Undergraduate Honors Theses

Chlamydia trachomatis is the most common bacterial agent of sexually transmitted infections worldwide and a common co-infection in AIDS patients. Chlamydial genital tract infections are often asymptomatic; therefore many infections go untreated and result in complications like chronic inflammation, ectopic pregnancy, and pelvic inflammatory disease. Chlamydia share a unique developmental cycle and under stress, can enter a state known as persistence, in which the bacteria are noninfectious but still viable. Removal of the stressor allows the chlamydiae to re-enter and complete the developmental cycle. Exposure to low-dose quinolones can cause the chlamydiae to enter persistence and halt the developmental cycle. …

Evaluation Of Tulane Virus As A Surrogate For The Study Of Human Norovirus, Sabastine Eugene Arthur

Graduate Theses and Dissertations

Among all known causes of acute gastroenteritis, human noroviruses (HuNoV) are the primary cause (68%) of outbreaks and are associated with 78% of illnesses, 46% of hospitalizations, and 86% of deaths. The main obstacle to studying the pathogenesis of HuNoV is the lack of cell culture system and small animal model. Murine norovirus (MNV) and feline calicivirus (FCV) have been utilized as model surrogate viruses to study HuNoV. In this research, a more recent surrogate virus, Tulane virus (TV), was evaluated for physicochemical stability and environmental persistence. The primary goal was to determine the suitability of TV as a surrogate …

Characterization And Investigation Of Fungi Inhabiting The Gastrointestinal Tract Of Healthy And Diseased Humans, Mallory J. Suhr

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

Gastrointestinal microbiome studies have failed to include fungi in total community analyses. As a result, their diversity and function in the gut is poorly understood. Recent work has begun to uncover the role intestinal fungi play in diet, immune system development, interactions with other microorganisms in the gut, and pathogenesis of diseases. Advances in sequencing technologies allow for the ability to profile the fungal gut microbiome (“mycobiome”) in healthy and diseased states. This thesis explores the mycobiome in 1) healthy humans with a vegetarian diet and 2) pediatric small bowel transplant recipients that develop fungal bloodstream infections.

The gut mycobiome …

Viral Bimolecular Fluorescence Complementation: A Novel Tool To Study Intracellular Vesicular Trafficking Pathways, Brennan S Dirk, Rajesh Abraham Jacob, Aaron L Johnson, Emily N Pawlak, P Craig Cavanagh, Logan Van Nynatten, S M Mansour Haeryfar, Jimmy D. Dikeakos

Microbiology & Immunology Publications

The Human Immunodeficiency Virus type 1 (HIV-1) accessory protein Nef interacts with a multitude of cellular proteins, manipulating the host membrane trafficking machinery to evade immune surveillance. Nef interactions have been analyzed using various in vitro assays, co-immunoprecipitation studies, and more recently mass spectrometry. However, these methods do not evaluate Nef interactions in the context of viral infection nor do they define the sub-cellular location of these interactions. In this report, we describe a novel bimolecular fluorescence complementation (BiFC) lentiviral expression tool, termed viral BiFC, to study Nef interactions with host cellular proteins in the context of viral infection. Using …

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring, Debra A. Benator, Angelo Elmi, Manuel D. Rodriguez, Howard B. Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

New Functionally-Enhanced Soy Proteins As Food Ingredients With Anti-Viral Activity, Aizhan Sabirzhanovna Turmagambetova, Nadezhda Sergeevna Sokolova, Andrey Pavlinovich Bogoyavlenskiy, Vladimir Eleazvich Berezin, Mary Ann Lila, Diana M. Cheng, Vyacheslav Dushenkov

Publications and Research

Respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. Cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique A-type proanthocyanidins. Soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. Recently, it was demonstrated that edible proteins can efficiently sorb and concentrate cranberry polyphenols, including anthocyanins and proanthocyanins, providing greatly stabilized matrices suitable for food products. The combination of cranberry and soy phytoactives may be an effective dietary anti-viral resource. Anti-viral properties of both cranberry juice-enriched …

Fluoroquinolone-Resistant Tuberculosis: Implications In Settings With Weak Healthcare Systems, Kauser Jabeen, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Fluoroquinolones (FQ) play an essential role in the treatment and control of multidrug-resistant tuberculosis (MDR-TB). They are also being evaluated as part of newer regimens under development for drug-sensitive TB. As newer FQ-based regimens are explored, knowledge of FQ resistance data from high TB burden countries becomes essential. We examine available FQ resistance data from high TB burden countries and demonstrate the need for comprehensive surveys to evaluate FQ resistance in these countries. The factors driving FQ resistance in such conditions and the cost of such resistance to weak healthcare systems are discussed. The need for a comprehensive policy for …

Helicobacter Pylori: Genomic Insight Into The Host-Pathogen Interaction, Kathryn P. Haley, Jennifer A. Gaddy

Peer Reviewed Articles

The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the …

Genome-Wide Comparison Of Pu.1 And Spi-B Binding Sites In A Mouse B Lymphoma Cell Line, Lauren A. Solomon, Stephen K. H. Li, Jan Piskorz, Li S. Xu, Rodney P. Dekoter

Microbiology & Immunology Publications

Background

Spi-B and PU.1 are highly related members of the E26-transformation-specific (ETS) family of transcription factors that have similar, but not identical, roles in B cell development. PU.1 and Spi-B are both expressed in B cells, and have been demonstrated to redundantly activate transcription of genes required for B cell differentiation and function. It was hypothesized that Spi-B and PU.1 occupy a similar set of regions within the genome of a B lymphoma cell line.

Results

To compare binding regions of Spi-B and PU.1, murine WEHI-279 lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1 or Spi-B. Anti-FLAG chromatin …

Inclusion Of Fermented Foods In Food Guides Around The World, Stephanie N. Chilton, Jeremy P. Burton, Gregor Reid

Microbiology & Immunology Publications

Fermented foods have been a well-established part of the human diet for thousands of years, without much of an appreciation for, or an understanding of, their underlying microbial functionality, until recently. The use of many organisms derived from these foods, and their applications in probiotics, have further illustrated their impact on gastrointestinal wellbeing and diseases affecting other sites in the body. However, despite the many benefits of fermented foods, their recommended consumption has not been widely translated to global inclusion in food guides. Here, we present the case for such inclusion, and challenge health authorities around the world to consider …

Immunotherapy For Human Breast Cancer, Nasrah Ali Al Kamal

Browse all Theses and Dissertations

Al Kamal, Nasrah. M.S. Program of Microbiology and Immunology, Wright State University, 2015.Immunotherapy for Human Breast Cancer. The study focuses on the methodologies that are used in breast cancer therapy. The review finds major evolutions of these methods and the influence they have made on the increased survival rates in cancer patients. There is also a projection of the processes that are involved in the therapy practices and the way the protocols have been improved over time. The various stages of cancer treatment project the various aspects of better performance articulations in the therapy sector. There is also reference to …

The Frequency Of Ticks Carrying Rickettsia Sp., Sarah C. Canterberry, Daniel J. Bennett, Robert J. Wiggers

Faculty Publications

No abstract provided.

Making The Leap From Research Laboratory To Clinic: Challenges And Opportunities For Next-Generation Sequencing In Infectious Disease Diagnostics., Brittany Goldberg, Heike Sichtig, Chelsie Geyer, Nathan Ledeboer, George M Weinstock

Pediatrics Faculty Publications

Next-generation DNA sequencing (NGS) has progressed enormously over the past decade, transforming genomic analysis and opening up many new opportunities for applications in clinical microbiology laboratories. The impact of NGS on microbiology has been revolutionary, with new microbial genomic sequences being generated daily, leading to the development of large databases of genomes and gene sequences. The ability to analyze microbial communities without culturing organisms has created the ever-growing field of metagenomics and microbiome analysis and has generated significant new insights into the relation between host and microbe. The medical literature contains many examples of how this new technology can be …

Early Initiation Of Antiretroviral Therapy Can Functionally Control Productive Hiv-1 Infection In Humanized-Blt Mice, Qingsheng Li, For Yue Tso, Guobin Kang, Wuxun Lu, Yue Li, Wenjin Fan, Zhe Yuan, Christopher J. Destache, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background—Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early anti-retroviral therapy (ART); however its underlying mechanism needs to be studied with a suitable animal model. Recently, humanized-BLT (bone marrow, liver and thymus) mouse (hu-BLT) was shown to be an excellent model for studying HIV-1 infection. We thus tested the feasibility of studying functional control of HIV-1 infection using hu-BLT mice.

Methods—Animals in three treatment groups (Rx-6h, Rx-24h, Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24 or 48 hours post-infection and continued daily for two weeks. …

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

Application Of Supervised Machine Learning Algorithms For Rapid Identification Of Mrsa Pfge Strain Types, Michael L. Bernauer

Biomedical Informatics Seminar Series (BioMISS)

Introduction: Pulsed-field gel electrophoresis (PFGE) is a molecular typing method used in epidemiologic surveillance of MRSA. PFGE relies on electrophoretic migration of restricted DNA fragments, resulting in characteristic fingerprints which can be used to classify organisms. Current methods of analysis, such as Gel Compar II and BioNumerics rely on unsupervised hierarchical clustering algorithms to group organisms based on pairwise similarity. These methods are labor intensive, often requiring a significant amount of user intervention and oversight. This study presents an automated approach to PFGE typing to reduce the amount of user involvement and time required for analysis.

Methods: A total of …

Adar1 Facilitates Hiv-1 Replication In Primary Cd4+ T Cells., Eloy Cuadrado, Thijs Booiman, John L Van Hamme, Machiel H Jansen, Karel A Van Dort, Adeline Vanderver, Gillian I Rice, Yanick J Crow, Neeltje A Kootstra, Taco W Kuijpers

Neurology Faculty Publications

Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of …

Herpes Virus Infections, Inflammatory Markers And Risk Of Developing T2dm And Cvd: An Analysis Of Nhanes With Adults, Aged 20-49, 1999-2010, Margarita Irizarry-De La Cruz

Walden Dissertations and Doctoral Studies

Herpes simplex viruses (HSVs), are among the most virulent and widespread pathogens; they affect 60-90% of the population worldwide. Substantial evidence indicates a possible association between pathogens and chronic disease. HSVs, among other viruses, have been associated with increased risk for inflammatory diseases. However, prior findings have been inconsistent on the role of infection in triggering autoimmune response and chronic disease. This study builds on the premise that pathogens can induce an inflammatory response and increase the risk for disease development. A representative U.S. sample from NHANES, a national population-based cross-sectional survey, was used to examine the relationship between HSVs …

A Nuclear Fraction Of Turnip Crinkle Virus Capsid Protein Is Important For Elicitation Of The Host Resistance Response, Sung-Hwan Kang, Feng Qu, Thomas J. Morris

Nebraska Center for Virology: Faculty Publications

The N-terminal 25 amino acids (AAs) of turnip crinkle virus (TCV) capsid protein (CP) are recognized by the resistance protein HRT to trigger a hypersensitive response (HR) and systemic resistance to TCV infection. This same region of TCV CP also contains a motif that interacts with the transcription factor TIP, as well as a nuclear localization signal (NLS). However, it is not yet known whether nuclear localization of TCV CP is needed for the induction of HRT-mediated HR and resistance. Here we present new evidence suggesting a tight correlation between nuclear inclusions formed by CP and the manifestation of HR. …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Genebased Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …