Immunology and Infectious Disease Commons^™

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

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 …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Characterization Of The Roles Of Carma3 And Bcl10 In Virus-Triggered Rig-I/Mavs Signaling Pathway, Zhicheng Zhou Mr

Dissertations and Theses (Open Access)

After RNA virus infection, the innate immunity utilizes RIG-I family of receptors in the cytoplasm to initiate the production of type-I IFNs and proinflammatory cytokines by mitochondrial protein MAVS, which forms a prion-like structure to recruit TBK1and IKK complex to activate IRF3 and NF-κB, respectively. Herein, we revealed the important roles of CARMA3 and BCL10 in RIG-I/MAVS signaling pathway for the first time. CARMA3 or BCL10 deficient cells exhibited partially defective NF-κB activation but hyperactivation of TBK1-IRF3 signaling pathway upon ssRNA virus infection. It led to less production of IL6 but more production of type I IFNs and resulted in …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations and Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

Osteomyelitis Associated With Nocardiopsis Composta In A Dog, Elisa N. Salas, Debra Royal, Lance Kurz, J. Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Osteomyelitis can be caused by bacterial or fungal agents or may be idiopathic. Cocci, bacilli, and filamentous bacteria such as members of the Actinomycetes have all been determined to be causes of osteomyelitis. Differential diagnoses for Gram-positive filamentous rods in the family Actinomycetales causing osteomyelitis in the dog, include members of the more frequently encountered genera Nocardia and Actinomyces. Bacteria gain access to the bone via several routes but are most often associated with direct inoculation (such as percutaneous injuries, compound fractures, or secondary to foreign bodies such as surgical or other material including dirt and wood) and fracture …

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 …

Nsf Grant Helps Preserve Parasite Collections, Leslie Reed

Harold W. Manter Laboratory of Parasitology: Faculty Publications

The National Science Foundation has awarded a $500,000 grant that will allow four major parasite collections to be digitized. The collections are part of UNL's Harold W. Manter Laboratory of Parasitology. Scott Gardner (pictured) is the curator and director of the Manter Laboratory. A $500,000 grant from the National Science Foundation will allow the Harold W. Manter Laboratory of Parasitology to digitally preserve four major collections of parasite specimens donated to the University of Nebraska-Lincoln during the past five years.

Leukocyte Responsiveness To Exercise In Hcmv+ Individuals, Jared Nicholas Wilson

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Emerging research suggests that the lymphocyte immune response during exercise is amplified in individuals who are positive for human cytomegalovirus (HCMV+). However, the responses of monocytes and neutrophils in HCMV+ individuals are unknown. HCMV, a type of herpes virus, infects 50% or more of the adult population in the United States. This virus can become a cause for concern in individuals who have a compromised immune system, which has been shown to occur after high-intensity exercise.

Purpose: The purpose of this study was to characterize the lymphocyte, monocyte, and neutrophil responses to exercise in HCMV+ individuals.

Methods: Participants were …

Investigations Into The Incidence And Control Of Selected Parasites And Pathogens Which Infect Arkansas Horses, Stephanie Ann O'Berg Rainbolt

Graduate Theses and Dissertations

Parasite control is an important aspect of health management of horses, particularly the control of gastrointestinal (GI) parasites. Recently, treatment recommendations have involved selective use of anthelmintics in horses with fecal egg counts (FEC) greater than a specified threshold. The objectives of this study were; (1) to determine the prevalence of helminths in our area by egg and L3 determinations, (2) to determine if certain horses maintained low FEC, therefore eliminating the need to treat them on a year-round basis and (3) to determine the effectiveness of four common treatments (moxidectin, ivermectin (pioneer and generic), fenbendazole and pyrantel tartrate) via …

Phylogeny And Diversity Of Entamoeba In Cockroaches, With An Emphasis On Periplaneta Americana, Mustafa Husain Fakhri

Graduate Theses and Dissertations

While the parasitic Amoebozoan Entamoeba histolytica has been well-studied for its role in human pathogenesis, the biodiversity of invertebrate-inhabiting Entamoeba has scarcely been investigated. Using molecular methods, I searched for Entamoeba in the guts of cockroaches from four of the six Blattodean families. Entamoeba small-subunit rRNA genes were recovered from all eight species of cockroaches tested, five of which represent newly discovered hosts. Phylogenetic analysis of over 190 sequences revealed a novel and highly diverse clade of cockroach-inhabiting Entamoeba, separate from the clade predominated by vertebrate-inhabitants. These results double the known genetic diversity of Entamoeba and suggest that they may …

The Regulation Of Cathepsin L Activity By Estrogen And Bisphenols A & S: Relationship To Systemic Lupus Erythematosus, Dylan T. Cuva

Biology Honors Papers

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that is linked to increased levels of estrogen. Bisphenol A (BPA) is an environmental estrogen that may also play a role in SLE. BPA is used in the production of polycarbonate plastics and epoxy resins, including use in the creation of cans and plastic bottles. This study investigated the role of BPA and other bisphenols on enzyme activity in a murine model for SLE.

A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically …

The Effects Of Digestion On Innate Immunity, Rachel L. Luoma

Honors College Theses

Following a meal, an animal can exhibit dramatic shifts in its physiology that can result in rapid growth of the gut and heart, as well as a massive (>40-fold) increase in metabolic rate associated with the energetic costs of processing the meal. However, little is known about the effects of digestion on an important physiological trait: immune function. Thus, I tested the following competing hypotheses. First, digesting animals may upregulate their immune systems due to increased microbial exposure from ingested food. This hypothesis predicts that animals will exhibit greater immune function during digestion. Second, digesting animals may downregulate their …

Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Investigation Of Dual Stage Acridones As A Potent Malaria Treatment, Stephanie Huezo

Dissertations, Masters Theses, Capstones, and Culminating Projects

The need for potent antimalarials to prevent the emergence of drug resistant Plasmodium falciparum is urgent. Discovery of novel acridone chemotypes have shown promise for a new antimalarial drug treatment. Presently, two acridone chemotypes have intrinsic antimalarial potency against chloroquine sensitive and multidrug resistant parasites. Acridones lacking an N10 side chain are known as chemotype I acridones, whereas, chemotype II acridones are defined as having an alkyl side chain at the same position. The N10 substitution of chemotype II acridones is thought to target heme and inhibit hemozoin formation within the parasite’s digestive vacuole, and is known to provide synergistic …

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 …

Baylisascaris Spp. In Non-Raccoon Procyonid Hosts And Assessment Of Potential Risk Of Human Exposure, Max Carlin Parkanzky

Open Access Theses

Baylisascaris procyonis (Bp) is a large roundworm of the common raccoon (Procyon lotor) which serves as the definitive host. Bp is an important cause of clinical larva migrans, including severe neurological disease, across numerous taxa including humans. Other procyonids, as well as occasionally dogs, can act as definitive hosts for this or other Baylisascaris spp. Many of these animals are becoming more common as household pets, posing a risk to people who come in contact with these animals. We have investigated whether patent Baylisascaris spp. infection exists in captive non-raccoon procyonids and if humans who contact these animals …

Aggregatibacter Actinomycetemcomitans Cytolethal Distending Toxin Activates The Nlrp3 Inflammasome In Human Macrophages Leading To The Release Of Pro-Inflammatory Cytokines, Bruce J. Shenker, David M. Ojcius, Lisa P. Walker, Ali Zekavat, Monika Damek Scuron, Kathleen Boesze-Battaglia

All Dugoni School of Dentistry Faculty Articles

The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive …

Relationship Between Heat-Labile Enterotoxin Secretion Capacity And Virulence In Wild Type Porcine-Origin Enterotoxigenic Escherichia Coli Strains, Prageeth Wijemanne, Jun Xing, Emil M. Berberov, David B. Marx, David H. Francis, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Heat-labile enterotoxin (LT) is an important virulence factor secreted by some strains of enterotoxigenic Escherichia coli (ETEC). The prototypic human-origin strain H10407 secretes LT via a type II secretion system(T2SS). We sought to determine the relationship between the capacity to secrete LT and virulence in porcine-origin wild type (WT) ETEC strains. Sixteen WT ETEC strains isolated from cases of severe diarrheal disease were analyzed by GM1ganglioside enzyme- linked immunosorbent assay tomeasure LT concentrations in culture supernatants. All strains had detectable LT in supernatants by 2 h of culture and 1 strain, which was particularly virulent in gnotobiotic piglets (3030-2), had …

Environmental Microbes And Uveitis: Is Microbial Exposure Always Bad?, Chandirasegaran Massilamany, A. Gangaplara, J. Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The eye generally is considered to be an immune-privileged organ, but this notion is being increasingly challenged as ocular antigens can be expressed in the generative lymphoid organs, resulting in attainment of self-tolerance. What triggers a break in this tolerant state is a fundamental question in autoimmunity research. The general belief is that exposure to environmental microbes can break self-tolerance in genetically susceptible individuals, leading to the induction of autoimmune responses. The molecular mimicry hypothesis has been proposed as one major mechanistic, pathway through which microbes, by generating crossreactive immune responses, can induce ocular damage of the kind that might …

Taphonomic Considerations For The Analysis Of Parasites From Archaeological Contexts, Johnica J. Morrow, Dario Piombino-Mascali, Karl J. Reinhard

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Discusses the role of taphonomy in archaeaoparasitology investigations. Enumerates various factors involved in preservation techniques. Gives cases from Lithuania, Belgium, and Italy. Concludes that considering the taphonomic factors associated with archaeological materials is a vital component in the interpretation of archaeoparasitological data.

First Record Of The Invasive Asian Fish Tapeworm Bothriocephalus Acheilognathi In Honduras, Central America, Guillermo Salgado-Maldonado, Wilfredo A. Matamoros, Brian R. Kreiser, Juan Manuel Caspeta-Mandujano, Edgar F. Mendoza-Franco

Faculty Publications

This paper provides the first report of the invasive Asian fish tapeworm, Bothriocephalus acheilognathi Yamaguti, 1934, in Honduras. The cestode was found in Profundulus portillorum (Cyprinodontiformes: Profundulidae), which represents a new host record, and which is a member of a genus faced with a variety of conservation challenges, now potentially complicated by the presence of this pathogenic cestode. Nearly complete sequence data from the ITS-1 5.8S and ITS-2 regions corroborate the determination based on morphological characteristics. Several species of carp were introduced to Honduras for aquaculture purposes in the early 1980s and the presence of the Asian fish tapeworm in …

Ectoparasitism Shortens The Breeding Season In A Colonial Bird, Charles R. Brown, Mary Bomberger Brown

School of Natural Resources: Faculty Publications

When blood-feeding parasites increase seasonally, their deleterious effects may prevent some host species, especially those living in large groups where parasites are numerous, from reproducing later in the summer. Yet the role of parasites in regulating the length of a host’s breeding season—and thus the host’s opportunity for multiple brooding—has not been systematically investigated. The highly colonial cliff swallow (Petrochelidon pyrrhonota), a temperate-latitude migratory songbird in the western Great Plains, USA, typically has a relatively short (eight to nine week) breeding season, with birds rarely nesting late in the summer. Colonies at which ectoparasitic swallow bugs (Oeciacus vicarius) were experimentally …

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 …

Evolution Of Bat-Trypanosome Associations And The Origins Of Chagas Disease, Christian Miguel Pinto

Dissertations, Theses, and Capstone Projects

Trypanosoma cruzi is a genetically diverse parasite that causes Chagas disease, one of the most important zoonoses in the Americas. This generalist parasite of mammals belongs to a clade mostly comprised of bat parasites, the T. cruzi clade. The origins (i.e., biogeographic history and evolution of hosts associations) of this parasite are far from being understood, and the main areas that need further study are: species limits within T. cruzi sensu lato, further studies on the diversity of T. cruzi clade members and their hosts, and research on adaptations of the hosts to trypanosome infections. In this dissertation I explore …

Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn

Dissertations, Theses, and Capstone Projects

Orchestrated expression of multiple genes residing in the complex TCRα/δ/Dad1 locus requires tight control from multiple cis-acting elements. The TCRα locus control region (LCR), is positioned between TCRα and Dad1 gene, and has been implicated in the differential expression of both genes. In this study, we focus our work on the hypersensitive site (HS)1 prime (HS1'), located 3' of the classical Eα enhancer, within the TCRα LCR. We investigated its non- redundant role in TCRα expression in thymic and peripheral T cells as assayed by in vivo and in vitro studies. Furthermore, formation of HS1' in both lymphoid and …

The Leishmania Years At Unl (Or, My Life As A Cell Biologist, 1966-1981), John J. Janovy Jr.

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Slides for a talk during which Professor Janovy discussed the methods he used in researching Leishmania during the years 1966-1981. Includes lists of references.

A New Method For Estimating Species Age Supports The Coexistence Of Malaria Parasites And Their Mammalian Hosts, Joana C. Silva, Amy Egan, Cesar Arze, John L. Spouge, David G. Harris

Harold W. Manter Laboratory of Parasitology: Library Materials

Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including …