Immunology and Infectious Disease Commons^™

Microsporidia Spore Adherence And Host Cell Infection In Vitro, Cory A. Leonard

Electronic Theses and Dissertations

Microsporidia infect invertebrate and vertebrate animals. Human pathogenic microsporidia are associated with severe disease in immunocompromised individuals, and mostly asymptomatic infection in the immunocompetent. Treatment options for microsporidiosis are limited, incompletely effective, and associated with toxicity. Furthermore, microsporidia infection of healthy individuals is poorly understood, and the consequences of asymptomatic infection have not been determined. Little is known about the molecular mechanisms of microsporidia infection, but such information is essential for the development of new therapies. Spores adhere to host cell surfaces in vitro. Our laboratory has focused on determining specific host cell and microsporidia spore surface participants in spore …

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

Dissertations and Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). …

Coccidia Of Gerbils From Mongolia, Ethan Thomas Jensen

School of Biological Sciences: Dissertations, Theses, and Student Research

In this study, gerbils collected in the Mongolia over the summers of 2009-2012 were examined for coccidia. In total, 171 gerbils of three species from 22 localities were examined for coccidia. Coccidian oocysts were identified from 21 gerbils, but those found in 1 of those gerbils were probably pseudoparasites of the host from which they were recovered. From the remaining 20 gerbils, 7 morphotypes of Eimeria and 1 morphotype of Isospora were identified. Four of the 7 morphotypes of Eimeria were attributed to new species which were described in this study. In addition, 10 previously described species of Eimeria were …

Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco

Dissertations

Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was …

Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador

School of Veterinary and Biomedical Sciences: Faculty Publications

In sugar cataract formation in rats, aldose reductase (AR) actitvity is not only linked to lenticular sorbitol (diabetic) or galactitol (galactosemic) formation but also to signal transduction changes, cytotoxic signals and activation of apoptosis. Using both in vitro and in vivo techniques, the interrelationship between AR activity, polyol (sorbitol and galactitol) formation, osmotic stress, growth factor induction, and cell signaling changes have been investigated. For in vitro studies, lenses from Sprague Dawley rats were cultured for up to 48 hrs in TC-199-bicarbonate media containing either 30 mM fructose (control), or 30 mM glucose or galctose with/without the aldose reductase inhibitors …

Association Study Of Common Genetic Variants And Hiv- 1 Acquisition In 6,300 Infected Cases And 7,200 Controls, Paul J. Mclaren, Cedric Coulonges, Stephan Ripke, Leonard H. Van Den Berg, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Judith Dalmau, Steven G. Deeks, Olivier Delaneau, Andrea De Luca, James J. Goedert, David W. Haas, Joshua T. Herbeck, Sekar Kathiresan, Gregory D. Kirk, Olivier Lambotte, Ma Luo, Simon Mallal, Danielle Van Manen, Javier Martinez-Picado, Florencia Pereyra, Francis A. Plummer, Guido Poli, Ying Qi, Pierre Rucart, Manj S. Sandhu, Patrick R. Shea, Hanneke Schuitemaker, Ioannis Theodorou, Fredrik Vannberg, Jan Veldink, Bruce D. Walker, Amy C. Weintrob, Cheryl Winkler, Steven M. Wolinsky, Amalio Telenti, David B. Goldstein, Paul I. W. De Bakker, Jean-Francois Zagury, Jacques Fellay

Biology Faculty Articles

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the …

P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X₄ is assembled with the receptor P2X₇ and its associated pore, pannexin-1. ATP induces ROS …

Spatially Explicit Modeling Of Schistosomiasis Risk In Eastern China Based On A Synthesis Of Epidemiological, Environmental, And Intermediate Host Genetic Data, Matthias Schrader, Torsten Hauffe, Zhijie Zhang, George M. Davis, Fred Jopp, Justin V. Remais, Thomas Wilke

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable …

In-Water Hull Cleaning And Filtration System: In-Water Cleaning Trials, Department Of Fisheries

Fisheries Occasional Publications

No abstract provided.

In-Water Hull Cleaning System Cost & Cost Benefit Analysis, Department Of Fisheries

Fisheries Occasional Publications

No abstract provided.

Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication By Regulating Cell Survival And Cellular Gene Expression, Phat X. Dinh, Anshuman Das, Rodrigo Franco, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from …

Characterization Of The Gut Microbiota And Colitogenic Bacterial Species In Core 1 O-Glycans Deficient Mice, Maria E. Perez-Munoz

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

Mucus is one important component of the intestinal mucosal barrier, and loss of its functionality is associated with colitis in humans and mice. Mice deficient in core 1 O-glycans (TM-IEC C1galt1^-/-) display a thinner mucus layer upon mutation of the glycosyltransferase enzyme (C1GALT1) responsible for core 1 O-glycans attachment, thus constituting an experimental model for human Ulcerative Colitis (UC). Under conventional conditions, these mice experience spontaneous inflammation of the colon. However, the exact role of the microbiota in colitis development in these mice has not been systematically investigated.

Aimed to gain insights into the role of …

Ectoparasites Of The Virginia Opossum (Didelphis Virginiana), Raccoon (Procyon Lotor), And Striped Skunk (Mephitis Mephitis) From Keith County, Nebraska, Lance A. Durden, Dennis J. Richardson

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

Six Virginia opossums (Didelphis virginiana), nine raccoons (Procyon lotor) and one striped skunk (Mephitis mephitis) collected from Keith County Nebraska were examined for ectoparasites. All three host species were parasitized by adults of the American dog tick, Dermacentor variabilis. Opossums were also parasitized by the flea Pulex simulans and the tiny fur mite Didelphilichus serri­fer; the latter species represents a new state record for Nebraska. Raccoons were also parasitized by P. simulans and by the lago­morph-associated flea Euhoplopsyllus glacialis affinis, whereas the skunk was also parasitized by the chewing louse Neotrichodectes …

Estudios Científicos En El Estado De Hidalgo Y Zonas Aledañas, Volumen Ii, Griselda Pulido-Flores, Scott Monks

Zea E-Books Collection

Los 16 capítulos que conforman este libro son una contribución al conocimiento de la biodiversidad y conservación de los recursos naturales en el estado de Hidalgo, México.

Se aborda el derecho de propiedad intelectual en la biodiversidad, citando algunos ejemplos de México. Así mismo, se presenta un estudio de la biodiversidad y distribución de la herpetofauna en cuatro tipos de vegetación. Desde el punto de vista de la helmintología se presentan dos estudios de los helmintos parásitos de vertebrados silvestres; con nuevos registros de hospederos y localidades de algunas especies de helmintos para Hidalgo. También, se aborda el uso de …

Mycobacterium Bovis (Bovine Tuberculosis) Infection In North American Wildlife: Current Status And Opportunities For Mitigation Of Risks Of Further Infection In Wildlife Populations, Ryan S. Miller, Steven J. Sweeney

Zoonotics and Wildlife Disease: Publications

Mycobacterium bovis (M. bovis), the causative agent of bovine tuberculosis, has been identified in nine geographically distinct wildlife populations in North America and Hawaii and is endemic in at least three populations, including members of the Bovidae, Cervidae, and Suidae families. The emergence of M. bovis in North American wildlife poses a serious and growing risk for livestock and human health and for the recreational hunting industry. Experience in many countries, including the USA and Canada, has shown that while M. bovis can be controlled when restricted to livestock species, it is almost impossible to eradicate …

Diseases At The Livestock–Wildlife Interface: Status, Challenges, And Opportunities In The United States, Ryan S. Miller, Mathew L. Farnsworth, Jennifer L. Malmberg

Zoonotics and Wildlife Disease: Publications

In the last half century, significant attention has been given to animal diseases; however, our understanding of disease processes and how to manage them at the livestock–wildlife interface remains limited. In this study, we conduct a systematic review of the scientific literature to evaluate the status of diseases at the livestock–wildlife interface in the United States. Specifically, the goals of the literature review were three fold: first to evaluate domestic animal diseases currently found in the United States where wildlife may play a role; second to identify critical issues faced in managing these diseases at the livestock–wildlife interface; and third …

Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of …

Structural Mechanism Of Orthopoxvirus Sabotage Of Mhci Antigen Presentation, William Howard Mccoy Iv

All Theses and Dissertations (ETDs)

Immunomodulatory proteins that subvert major histocompatibility complex class I: MHCI) antigen presentation can help viruses to evade cytotoxic T-lymphocyte: CTL) detection and clearance. Cowpox virus, like other orthopoxvirus family members, is a large DNA virus, whose genomic termini encode numerous immunomodulatory genes, including two ER-resident MHCI saboteurs: CPXV012 and CPXV203). CPXV012 inhibits peptide loading of MHCI within the peptide-loading complex: PLC), while CPXV203 inhibits surface expression of both murine and human MHCI through the use of a C-terminal ER-retention sequence: KTEL). An association: direct or indirect) between CPXV203 and MHCI was first demonstrated in pull-down experiments. This doctoral work explores …

In Vitro Efficacy Of Clinically Available Drugs Against Growth And Viability Of Acanthamoeba Castellanii Keratitis Isolate Belonging To The T4 Genotype, Abdul Mannan Baig, Junaid Iqbal, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

The effects of clinically available drugs targeting muscarinic cholinergic, adrenergic, dopaminergic, and serotonergic receptors; intracellular calcium levels and/or the function of calcium-dependent biochemical pathways; ion channels; and cellular pumps were tested against a keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype. In vitro growth inhibition (amoebistatic) assays were performed by incubating A. castellanii with various concentrations of drugs in the growth medium for 48 h at 30°C. To determine amoebicidal effects, amoebae were incubated with drugs in phosphate-buffered saline for 24 h, and viability was determined using trypan blue exclusion staining. For controls, amoebae were incubated with the …

Efficacies Of Fenbendazole And Albendazole In The Treatment Of Commercial Turkeys Artificially Infected With Ascaridiadissimilis, Jessica Perkins

Animal Science Undergraduate Honors Theses

The goal of this research was to determine the extent of anthelmintic resistance that turkey roundworms, Ascaridiadissimilis, have developed to anti-parasitic chemicals used in commercial turkey operations. Roundworm infections in turkeys have resulted in monetary losses for the poultry industry for years, generally due to poor feed conversion. The infection itself is generally subclinical and many turkeys have a light to moderate worm burden. Since parasitisms are light, this leads to the infections being noticed only during processing.A. dissimilis infections consist of adult worms and developing larvae with the latter comprising most of the worm burden and causing the most …

Interaction Of Bacillus Anthracis Exosporium Protein Bcla With Complement Factor H And Spore Persistence In The Lung, Sarah A. Jenkins

Dissertations and Theses (Open Access)

Anthrax outbreaks in the United States and Europe and its potential use as a bioweapon have made Bacillus anthracis an interest of study. Anthrax infections are caused by the entry of B. anthracis spores into the host via the respiratory system, the gastrointestinal tract, cuts or wounds in the skin, and injection. Among these four forms, inhalational anthrax has the highest lethality rate and persistence of spores in the lungs of animals following pulmonary exposure has been noted for decades. However, details or mechanisms of spore persistence were not known. In this study, we investigated spore persistence in a mouse …

Analysis Of The Chondroitinase Operon Of Flavobacterium Columnare, Erin L. Sorlien

Senior Honors Projects

Analysis of the chondroitinase operon of Flavobacterium columnare

Erin Sorlien

Major

Cell and Molecular Biology, Chemistry

Advisor

Dr. David R. Nelson

Date

May 2, 2013

Keywords

Flavobacterium columnare, columnaris disease, chondroitin AC lyase, complementation, csl operon

Abstract
Flavobacterium columnare, an opportunistic bacterial pathogen of fish, is the causative agent of columnaris disease (CD). The bacterium is a Gram-negative rod that exhibits gliding motility and avidly forms biofilms. CD affects both wild and cultured freshwater fish, and continues to cause large economic losses to the fish farming industry. According to an investigation conducted by the National Animal Health Monitoring System, CD …

The Influence Of Immunization Route On The Adjuvant Effect Of Alpha-Galactosylceramide, Ameerah M. Wishahy

Dissertations and Theses (Open Access)

Potent vaccine formulations ideally include adjuvants to activate innate immune responses and enhance antigen-specific adaptive immunity. The synthetic glycolipid alpha-Galactosylceramide (α-GalCer) effectively activates the innate immune mediating NKT cells to produce cytokines and activate downstream immune cells, resulting in development of humoral and cell mediated immune responses to co-administered antigens. While a single intravenous immunization of α-GalCer strongly activates NKT cells, multiple doses by this route are well documented to induce anergy in NKT cells. Anergy is defined as the deficiency in NKT proliferation and cytokine production, including IL-4 and IFNγ. However, our studies have shown that two doses of …

Novel Imaging-Based Techniques Reveal A Role For Pd-1/Pd-L1 In Tumor Immune Surveillance In The Lung, Todd Bartkowiak

Dissertations and Theses (Open Access)

The binding of immune inhibitory receptor Programmed Death 1 (PD-1) on T cells to its ligand PD-L1 has been implicated as a major contributor to tumor induced immune suppression. Clinical trials of PD-L1 blockade have proven effective in unleashing therapeutic anti-tumor immune responses in a subset of patients with advanced melanoma, yet current response rates are low for reasons that remain unclear. Hypothesizing that the PD-1/PD-L1 pathway regulates T cell surveillance within the tumor microenvironment, we employed intravital microscopy to investigate the in vivo impact of PD-L1 blocking antibody upon tumor-associated immune cell migration. However, current analytical methods of intravital …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.

Emerging evidence suggests that host factors in the microenviromement …

Neuropathogenic Escherichia Coli K1 Does Not Exhibit Proteolytic Activities To Exert Its Pathogenicity, Junaid Iqbal, Mehak Rajan, Ruqaiyyah Siddiqu, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Background: Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood-brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogenicity.
Methods: Zymographic assays were performed using collagen and gelatin as substrates. The lysates of whole E. coli K1 strain E44, or E. coli K-12 strain HB101 were tested for proteolytic activities. The conditioned media were …

Enrollment In Yfv Vaccine Trial: An Evaluation Of Recruitment Outcomes Associated With A Randomized Controlled Double-Blind Trial Of A Live Attenuated Yellow Fever Vaccine, Paula M. Frew, Eve T. Shapiro, Lu Lu, Srilatha Edupuganti, Harry L. Keyserling, Mark J. Mulligan

Environmental & Global Health Faculty Research

This investigation evaluated several factors associated with diverse participant enrollment of a clinical trial assessing safety, immunogenicity, and comparative viremia associated with administration of 17-D live, attenuated yellow fever vaccine given alone or in combination with human immune globulin. We obtained baseline participant information (e.g., sociodemographic, medical) and followed recruitment outcomes from 2005 to 2007. Of 355 potential Yellow Fever vaccine study participants, 231 cases were analyzed. Strong interest in study participation was observed among racial and ethnically diverse persons with 36.34% eligible following initial study screening, resulting in 18.75% enrollment. The percentage of white participants increased from 63.66% (prescreened …

Emerging Partially Effective Vaccines: Ethical And Policy Considerations, Vincent Y. Ling J.D., M.S.

North Carolina Central University Science & Intellectual Property Law Review

No abstract provided.

Vaccination Of Balb/C Mice With The Na-Apr-1 M74 Hookworm Vaccine Generates Neutralizing Antibodies And A Potent Immune Response, Amar R. Jariwala, Xi Chen, Mark S. Pearson, Brian Keegan, Jill B. Brelsford, Jordan L. Plieskatt, Bin Zhan, Alex Loukas, Peter Hotez, Jeffrey M. Bethony

GW Research Days 2013

BACKGROUND

Human Hookworm Infection, a neglected tropical disease infects more than 600 million people around the world. Hookworms ingest hemoglobin containing erythrocytes and Necator americanus Aspartic Protease-1 wild type (Na-APR-1wt) a hemoglobinase cleaves hemoglobin to form Heme and Globin. Globin is further digested by other gut enzymes and the nutritional products are absorbed by the hookworm’s gut wall. Also, Heme which is toxic to hookworm is detoxified by the Necator americanus Glutathione Transferase-1 (Na-GST-1); a detoxification enzyme secreted by the gut of the hookworm. Necator americanus Aspartic Protease-1 M74 (Na-APR-1 M74) is a new …