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Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5-fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. Ad5-R3 …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity Via Interferon-Beta And Indoleamine-2,3-Dioxygenase, Michael B. Cheung

USF Tampa Graduate Theses and Dissertations

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in young children worldwide, accounting for an estimated 33.8 million cases of respiratory disease, over 3 million of which require hospitalization, and between 66,000 and 199,000 deaths in this susceptible population. Additionally, severe RSV infection early in life is associated with an increased risk of wheeze and other airway disorders later in life. Despite this, there is currently no vaccine or economically reasonable prophylactic regimen to prevent infection. While disease is typically more severe in infancy RSV can infect throughout the lifespan repeatedly as the …

Staphylococcus Aureus Coordinates Leukocidin Expression And Pathogenesis By Sensing Metabolic Fluxes Via Rpirc, Divya Balasubramanian, Elizabeth A Ohneck, Jessica Chapman, Andy Weiss, Min Kyung Kim, Tamara Reyes-Robles, Judy Zhong, Lindsey N. Shaw, Desmond S. Lun, Beatrix Ueberheide, Bo Shopsin, Victor J Torres

Molecular Biosciences Faculty Publications

Staphylococcus aureus is a formidable human pathogen that uses secreted cytolytic factors to injure immune cells and promote infection of its host. Of these proteins, the bicomponent family of pore-forming leukocidins play critical roles in S. aureus pathogenesis. The regulatory mechanisms governing the expression of these toxins are incompletely defined. In this work, we performed a screen to identify transcriptional regulators involved in leukocidin expression in S. aureus strain USA300. We discovered that a metabolic sensor-regulator, RpiRc, is a potent and selective repressor of two leukocidins, LukED and LukSF-PV. Whole-genome transcriptomics, S. aureus exoprotein proteomics, and metabolomic analyses revealed that …

Trypanosoma Brucei Tif2 And Trf Suppress Vsg Switching Using Overlapping And Independent Mechanisms, Sanaa E. Jehi, Vishal Nanavaty, Bibo Li Ph.D.

Biological, Geological, and Environmental Faculty Publications

Trypanosoma brucei causes debilitating human African trypanosomiasis and evades the host's immune response by regularly switching its major surface antigen, VSG, which is expressed exclusively from subtelomeric loci. We previously showed that two interacting telomere proteins, TbTRF and TbTIF2, are essential for cell proliferation and suppress VSG switching by inhibiting DNA recombination events involving the whole active VSG expression site. We now find that TbTIF2 stabilizes TbTRF protein levels by inhibiting their degradation by the 26S proteasome, indicating that decreased TbTRF protein levels in TbTIF2-depleted cells contribute to more frequent VSG switching and eventual cell growth arrest. Surprisingly, although TbTIF2 …

Characterization Of Nuclear Factor-Kappab Binding Sites In The Freshwater Snail, Biomphalaria Glabrata, Laura E. Deneckere

Lawrence University Honors Projects

Biomphalaria glabrata is an intermediate snail host for the digenean trematode, Schistosoma mansoni, which causes the human disease schistosomiasis. A lot of research has focused on the snail-schistosome interaction, especially in regards to the immune response of the snail. The nuclear factor-kappaB (NF-κB) pathway, which is involved in regulating the immune response, can be triggered by the Toll-like receptor (TLR) signaling pathway. However, not much is known about the specific molecular mechanisms regulating these responses. Both NF-κB and TLR homologues have recently been reported in B. glabrata so it is of great interest to determine if BgNF-κB can regulate …

Membrane Insertion For The Detection Of Lipopolysaccharides: Exploring The Dynamics Of Amphiphile-In-Lipid Assays, Loreen R. Stromberg, Nicolas W. Hengartner, Kirstie L. Swingle, Rodney A. Moxley, Steven W. Graves, Gabriel A. Montaño, Harshini Mukundan

School of Veterinary and Biomedical Sciences: Faculty Publications

Shiga toxin-producing Escherichia coli is an important cause of foodborne illness, with cases attributable to beef, fresh produce and other sources. Many serotypes of the pathogen cause disease, and differentiating one serotype from another requires specific identification of the O antigen located on the lipopolysaccharide (LPS) molecule. The amphiphilic structure of LPS poses a challenge when using classical detection methods, which do not take into account its lipoglycan biochemistry. Typically, detection of LPS requires heat or chemical treatment of samples and relies on bioactivity assays for the conserved lipid A portion of the molecule. Our goal was to develop assays …

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of …

Development Of A Novel Self-Propagating Prssv-Vsv G Hybrid Replicon As A Vector For Inducing Broad Prrsv Protection, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Throughout successive cycles of Pork Check-off funding, our laboratories (Pattnaik’s and Osorio’s labs) have consistently produced new and fundamental information on: (i) the immunologic mechanisms that are important for protection against PRRSV infection, (ii) the structural basis for induction of PRRSV-neutralizing antibodies which are significant for conferring protective immunity, (iii) the possibility of producing a rationally-designed new generation DIVA vaccine that would offer more efficacious protection, and (iv) the presence of conserved B- and T-cell epitopes in the structural and nonstructural proteins (NSPs) of PRRSV.

Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., Michelle L. Mason

Biological Sciences Undergraduate Honors Theses

Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties. …

Immunomodulation Of Breast Cancer Cells For Whole Tumor Vaccination, Kristina G. Maxwell

Biomedical Engineering Undergraduate Honors Theses

Hematogenous metastasis causes 90% of breast cancer-related deaths.Current therapies include chemotherapy and irradiation following surgery. These therapies are very harmful to the human body and do not elicit an anti-tumor immune response. To create a novel therapeutic, an autologous vaccine increasing the immunogenicity of non immunogenic breast cancer cell lines has been proposed.

To create this vaccine, 4T1 mouse mammary breast cancer cells have been selected as the desired cell line to treat. They are non immunogenic and highly invasive. In order to increase their immunogenicity, first projected, was the addition of cytokines to 4T1 cells to increase the expression …

Rerouting Pre-Existing Host Vaccine-Induced Immunity To Wards Breast Cancer, Bharat Kumar Reddy Chaganty

Dissertations and Theses (Open Access)

For decades, investigators have attempted to activate the immune system to prevent cancer metastasis or recurrence; however, owing to host immune tolerance to cancer antigens and the immunosuppressive environment at tumor sites, many such attempts have failed. The recent success of anti-CTLA4, PD-L1 and PD-1 antibodies targeting immune checkpoint pathways and HPV vaccines has renewed hope that patient survival can be increased through enhancing T-cell responses. We propose to test a novel approach that may bypass host immune tolerance to cancer cells. We hypothesize that host T-cell immunity acquired through vaccination against or natural infection with infectious diseases—e.g., influenza—can be …

Poster: Embryonic Stem Cell Research, Emillie Partridge

Best Integrated Writing

This poster presentation by Partridge provides information about stem cell research and the controversy surrounding it.

A Subset Of Latency-Reversing Agents Expose Hiv-Infected Resting Cd4+ T-Cells To Recognition By Cytotoxic T-Lymphocytes., R. Brad Jones, Stefanie Mueller, Rachel O'Connor, Katherine Rimpel, Derek D Sloan, Allison S. Thomas, Sara Karandish, Szu-Han Huang, +13 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Resting CD4+ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8+ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8+ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8+ T-cell clones as biosensors for HIV antigen expression. By testing …

Identification And Characterization Of Ion Channel Activity Of The M2 Protein From Influenza Virus D (Dm2), Jianing Liu

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

Viral ion channels are membrane proteins of influenza viruses that play essential roles in the replication cycle, which enables them to be targeted by antiviral drugs. M2 of influenza type A virus, BM2 of influenza type B virus, and CM2 from influenza type C virus have been characterized as ion channel proteins and antiviral drug amantadine was developed to control influenza type A virus. However, few studies have been conducted to clarify the properties of the M2 protein (DM2) of influenza type D virus, a novel influenza virus genus identified in 2014. To identify the ion channel activity of DM2, …

Comparison Of Interactive Voice Response (Ivr) With Paper Administration Of Instruments To Assess Functional Status, Sexual Function, And Quality Of Life In Elderly Men, Rc Rosen, Aj Stephens-Shields, Gr Cunningham, D Cifelli, D Cella, Jt Farrar, E Barrett-Connor, Ce Lewis, M Pahor, X Hou, Pj Snyder

Faculty, Staff and Students Publications

PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men = 65 years at each of two clinical sites. In …

Dengue-Induced Autophagy, Virus Replication And Protection From Cell Death Require Er Stress (Perk) Pathway Activation, E. Datan, S. G. Roy, G. Germain, N. Zali, J. E. Mclean, G. Golshan, S. Harbajan, R. A. Lockshin, Z. Zakeri

Publications and Research

Avirus that reproduces in a host without killing cells can easily establish a successful infection. Previously, we showed that dengue-2, a virus that threatens 40% of the world, induces autophagy, enabling dengue to reproduce in cells without triggering cell death. Autophagy further protects the virus-laden cells from further insults. In this study, we evaluate how it does so; we show that dengue upregulates host pathways that increase autophagy, namely endoplasmic reticulum (ER) stress and ataxia telangiectasiamutated (ATM) signaling followed by production of reactive oxygen species (ROS). Inhibition of ER stress or ATM signaling abrogates the dengueconferred protection against other cell …

Ct-Based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring For Fracture Prediction In Metastatic Femoral Lesions, Ta Damron, A Nazarian, V Entezari, C Brown, W Grant, N Calderon, Et Al.

Faculty, Staff and Students Publications

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and …

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific, V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty, Staff and Students Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies, Ms Siehr, Jl Noebels

Faculty, Staff and Students Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review, A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience, G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Glial Contributions To Neural Function And Disease, Mn Rasband

Faculty, Staff and Students Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Identification Of Novel Cyclic Lipopeptides From A Positional Scanning Combinatorial Library With Enhanced Antibacterial And Antibiofilm Activities, Nina Bionda, Renee M. Fleeman, César De La Fuente-Núñez, Maria C. Rodriguez, Fany Reffuveille, Lindsey N. Shaw, Irena Pastar, Stephen C Davis, Robert E W Hancock, Predrag Cudic

Molecular Biosciences Faculty Publications

Treating bacterial infections can be difficult due to innate or acquired resistance mechanisms, and the formation of biofilms. Cyclic lipopeptides derived from fusaricidin/LI-F natural products represent particularly attractive candidates for the development of new antibacterial and antibiofilm agents, with the potential to meet the challenge of bacterial resistance to antibiotics. A positional-scanning combinatorial approach was used to identify the amino acid residues responsible for driving antibacterial activity, and increase the potency of these cyclic lipopeptides. Screening against the antibiotic resistant ESKAPE pathogens revealed the importance of hydrophobic as well as positively charged amino acid residues for activity of this class …

Automated Assessment Of Disease Progression In Acute Myeloid Leukemia By Probabilistic Analysis Of Flow Cytometry Data, Bartek Rajwa, Paul K. Wallace, Elizabeth A. Griffiths, Murat Dundar

Bindley Publications

Objective: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods: The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian …

The Pseudorabies Virus Protein, Pul56, Enhances Virus Dissemination And Virulence But Is Dispensable For Axonal Transport, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Neurotropic herpesviruses exit the peripheral nervous system and return to exposed body surfaces following reactivation from latency. The pUS9 protein is a critical viral effector of the anterograde axonal transport that underlies this process. We recently reported that while pUS9 increases the frequency of sorting of newly assembled pseudorabies virus particles to axons from the neural soma during egress, subsequent axonal transport of individual virus particles occurs with wild-type kinetics in the absence of the protein. Here, we examine the role of a related pseudorabies virus protein, pUL56, during neuronal infection. The findings indicate that pUL56 is a virulence factor …

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse, Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

Jay Reddy Publications

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could …

Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …