Other Immunology and Infectious Disease Commons^™

Plants, Prions And Possibilities: Current Understanding And Significance Of Prion Uptake Into Plants, Tracy A. Nichols

USDA Wildlife Services: Staff Publications

Chronic wasting disease (CWD) is an infectious, neurodegenerative disease of deer (white-tailed and mule), elk, moose, sika deer and muntjac caused by a misfolded version of a normally occurring protein. The notion that CWD could be spread indirectly via the environment has been documented and accepted in the scientific community for quite some time. Deer and elk consume soil, inhale dust and lick objects that have infectious material on them, resulting in chronic, low dose exposure. Surface contamination of plants with urine or feces is likely an additional source of exposure via ingestion and has been modeled in the laboratory …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Characterization Of Induced Rnai Silencing Of Vaccinia Virus Essential Genes, Kewa Jiang

Honors Scholar Theses

Vaccinia virus (VACV) is a large double-stranded DNA virus and the prototypical member of the family Poxviridae and is most notable for its use as the vaccine that eradicated smallpox (variola virus). More recently, VACV has been used to develop recombinant vaccines and immunotherapies. However, many of these processes require VACV replication to be tightly controlled. RNA interference (RNAi) is a powerful tool for in vitro silencing of mRNAs that are complementary to 19-21 base pairs (bp) of double-stranded RNA (dsRNA). This project outlines the design and preliminary analysis of two inducible RNAi silencing constructs targeting multiple VACV essential genes …

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …

Non-Essentiality Of Alr And Muri Genes In Mycobacteria, Philion L. Hoff, Denise Zinniel, Raúl G. Barletta

UCARE Research Products

Amino acids are the building blocks of life. If DNA is the blueprint, amino acids are the lumber that proteins are built with. Proteins are built with left-handed, L- forms of amino acids. Bacteria have an essential cell wall component that happens to be an exception: peptidoglycan. Bacteria have enzymes called racemases that convert L- amino acid forms into right-handed, D- forms. Amino acids participate in many reactions with keto acids. Transaminases allow conversion between amino acids by transfer of an amino group.

Previous reports claimed there is no D-ala transaminase activity in mycobacteria and thus alr and murI genes …

Design Of Romp-Based Protein Mimics For Sirna Delivery, Brittany M. Deronde

Doctoral Dissertations

Designing delivery agents for therapeutics is an ongoing challenge. As treatments and desired cargoes become more complex, the need for improved delivery vehicles becomes critical. Excellent delivery vehicles must ensure the stability of the cargo, maintain the cargo’s solubility, and promote efficient delivery and release. In order to address these issues, many research groups have looked to nature for design inspiration. Proteins, such as HIV-1 TAT and Antennapedia homeodomain protein, are capable of crossing cellular membranes. However, due to the complexities of their structures, they are synthetically challenging to reproduce in the laboratory setting. Being able to incorporate the key …

Elucidating Binding, Fusion And Entry Of Human Metapneumovirus, Edita M. Klimyte

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) is a respiratory pathogen in the Paramyxoviridae family that infects nearly 100% of the world population. This enveloped RNA virus causes severe viral respiratory disease in infants, the elderly, and immunocompromised patients worldwide. Despite its prevalence and importance to human health, no therapies are available against this pathogen. Entry of paramyxoviruses into host cells generally requires the coordinated activity of the attachment glycoprotein, G, which interacts with a cell receptor, and the fusion glycoprotein, F, which promotes subsequent fusion of viral and cellular membranes. However, HMPV F is the primary viral protein mediating both binding and fusion …

The Impact Of Urbanization On Mosquito-Borne Viruses, Nikhita Puthuveetil

Undergraduate Research Posters

Mosquito-borne diseases such as yellow fever, dengue, and West Nile are rapidly emerging across the globe. Their emergence is often aided by the growth of their vector population, or the organisms that transmit the virus to the host. Urbanization and land use often destroys the habitat of the virus and its vector. However, the virus and its vector often survive despite the changes to its environment. The goal of this paper is to find out exactly how urbanization and changes in land use affect mosquito-borne viruses and how these viruses survive despite the destruction of their habitats. To understand how …

Role Of Adrenergic Neurons In Motor Control: Examination Of Cerebellar Purkinje Neurons In Mice Following Selective Adrenergic Cell Ablation In Vivo, Monica Mansour

Honors Undergraduate Theses

Phenylethanolamine-N-methyltransferase (Pnmt) is the enzyme that catalyzes the conversion of noradrenaline to adrenaline. These catecholamines are synthesized in the medulla of the adrenal gland and by some neurons of the central nervous system. The precise location of Pnmt action in the brain and its physiological significance are unknown. Prior studies led by Aaron Owji, a graduate student in Dr. Ebert’s laboratory, showed that mice with selectively ablated Pnmt cells show signs of neurological defects such as abnormal gait, weakened grip strength, lack of balance, reduced movement, and defective reflexes during tail suspension tests.

The cerebellum is a small section of …

High Diversity Of Trypanosoma Cruzi Discrete Typing Units Circulating In Triatoma In Western Mexico, Uyen T. Nguyen

All Master's Theses

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to domestic and sylvatic mammals via the feces of hematophagous hemiptera of the subfamily Triatominae (Reduviidae). Trypanosoma cruzi is found only in the Americas and displays remarkable genetic diversity. Seven discrete typing units (DTUs) are currently recognized (TcI–TcVI and TcBat). In Jalisco, Mexico, where Chagas disease has a high prevalence rate, TcI has historically been the only DTU reported. This study focused on the molecular identification of T. cruzi DTUs circulating in Triatoma near the Estación de Biología Chamela, on the southwest coast of Jalisco, Mexico. …

Plasmacytoid Dendritic Cell-Mediated Humoral Autoimmunity, Stephanie M. Dorta-Estremera Ph.D.

Dissertations & Theses (Open Access)

Humoral autoimmunity is characterized by the breakdown of B cell immune tolerance to self-antigens and consequent production of pathogenic autoantibodies. Plasmacytoid dendritic cells (pDCs), a potent type I interferon (IFN-I) producer, have been linked to the pathogenesis of systemic lupus erythematosus (SLE), a prototypic systemic humoral autoimmune disease. However, the cellular events that stimulate the development of humoral autoimmunity as a result of pDC activation have not been characterized. Moreover, the B cell subset(s) responsible for the generation of autoantibodies remains to be clearly identified.

The immunization of DNA-containing amyloids into non-autoimmune mice triggers the activation of pDCs and induction …

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations & Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Inhibition Of Sterile Danger Signals, Uric Acid And Atp, Prevents Inflammasome Activation And Protects From Alcoholic Steatohepatitis In Mice., Arvin Iracheta-Vellve, Jan Petrasek, Abhishek Satishchandran, Benedek Gyongyosi, Banishree Saha, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Background & Aims: The inflammasome is a well-characterized inducer of inflammation in alcoholic steatohepatitis (ASH). Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH.

Results:The sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection was …

Metabolic Danger Signals, Uric Acid And Atp, Mediate Inflammatory Cross-Talk Between Hepatocytes And Immune Cells In Alcoholic Liver Disease., Jan Petrasek, Arvin Iracheta-Vellve, Banishree Saha, Abhishek Satishchandran, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Inflammation defines the progression of ALD from reversible to advanced stages. Translocation of bacterial LPS to the liver from the gut is necessary for alcohol-induced liver inflammation. However, it is not known whether endogenous, metabolic danger signals are required for inflammation in ALD. Uric acid and ATP, 2 major proinflammatory danger signals, were evaluated in the serum of human volunteers exposed to a single dose of ethanol or in supernatants of primary human hepatocytes exposed to ethanol. In vitro studies were used to evaluate the role of uric acid and ATP in inflammatory cross-talk between hepatocytes and immune cells. The …

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 …

Preliminary Report On The Production Of A Shiga-Like Toxoid Fusion Protein As Associated With Novel Flic Vaccine, Michael Maulin

Georgia State Undergraduate Research Conference

No abstract provided.

A Novel Population Of Natural Killer Cells Plays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental African Trypanosomiasis, Deborah Frenkel

Doctoral Dissertations

Loss of humoral immune competence in T. brucei-infected mice is associated with the apoptotic depletion of splenic transitional, marginal zone and follicular B cells as well as a depletion of CD8⁺ T cells. This occurs rapidly after infection and impairs responses to vaccine antigens in addition to responses to newly arising VSG antigenic variants, leading to uncontrolled parasite growth and death of the infected mice. Infection-induced B2 B cell and CD8⁺ T cell loss requires the presence of a novel population of natural killer (NK) cells and is mediated by a perforin-dependent process consistent with perforin- and …

High-Throughput Data Analysis: Application To Micronuclei Frequency And T-Cell Receptor Sequencing, Mateusz Makowski

Theses and Dissertations

The advent of high-throughput sequencing has brought about the creation of an unprecedented amount of research data. Analytical methodology has not been able to keep pace with the plethora of data being produced. Two assays, ImmunoSEQ and the cytokinesisblock micronucleus (CBMN), that both produce count data and have few methods available to analyze them are considered.

ImmunoSEQ is a sequencing assay that measures the beta T-cell receptor (TCR) repertoire. The ImmunoSEQ assay was used to describe the TCR repertoires of patients that have undergone hematopoietic stem cell transplantation (HSCT). Several different methods for spectratype analysis were extended to the TCR …

Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin

Doctoral Dissertations

Aplastic Anemia is a rare immune mediated bone marrow failure disease that is mediated by autoreactive T cells that cause destruction to the stem, progenitor, and stromal cells in the bone marrow. Because little is known about the etiology of the disease, our lab has developed a major MHC mismatch GVHD model to examine cellular pathways in autoreactive T cells that contribute to disease. We examined three pathways that are important in T cell activation and differentiation and asked if they were important in the development of Aplastic Anemia. First, we were able to show that expression of active PKCθ …

Human Papillomavirus And The Gardasil Vaccine: Medicalization And The Gendering Of Bodies And Bodily Risk, Lauren Camara

Laurier Undergraduate Journal of the Arts

No abstract provided.