Immunology and Infectious Disease Commons^™

Discovery And Characterization Of Novel Antimicrobials Against Mycobacterium Tuberculosis, Carolina Rodrigues Felix

Electronic Theses and Dissertations

Tuberculosis disease is currently a global health emergency, causing the most deaths worldwide due a single infectious agent. Eradication of TB is hampered by lack of an effective vaccine and poor treatment options. During infection, host-derived cues such as hypoxia and starvation induce Mycobacterium tuberculosis to halt replication and become dormant, which leads to tolerance to front-line antibiotics used in the TB treatment. This dormant phenotype causes delayed clearance of M. tuberculosis, therefore a long treatment time is required for stable cure without relapse. Poor patient compliance increases the emergence of drug resistant strains, posing yet another challenge for the …

Characterization Of A Putative Hemolysin Expressed By Sneathia Amnii, A Preterm Birth-Associated Pathogen, Lizette Carrasco, Kimberly Jefferson

UROP Posters

The gram-negative bacteria Sneathia amnii is a poorly-characterized commensal of the female urogenital tract frequently associated with adverse clinical outcomes such as bacterial vaginosis (BV), amnionitis, and preterm labor. To investigate its potential role in virulence, we sought to identify and characterize virulence determinants produced by S. amnii in an effort to better understand the pathogenesis of infectious preterm birth. Through sequencing of the Sn35 genome (type strain of S. amnii), we identified two genes with amino acid sequence similarity and structural similarity to the filamentous hemagglutinin (FHA) protein of Bordetella pertussis and its Type Vb transporter. Because S. amnii …

A Behavioral And Neuroimmune System Model Of The Effects Of Chronic Low-Level Lead Exposure In Young Male C57bl/6j Mice, Mayra Gisel Flores-Montoya

Open Access Theses & Dissertations

Chronic low-level lead exposure reduces memory in children however the brain mechanisms mediating these effects are not known. In previous studies we showed that early lead exposure reduced olfactory memory and exploratory behavior in young mice, and reduced microglia cell density in hippocampus/dentate gyrus. The present studies aimed to identify additional behavioral tests that were sensitive to early low-level lead exposure in young mice; and to examine whether microglia upregulated factors known to promote cell migration. Seventy-two C57BL/6J male mice were exposed to 0 ppm (controls), 30 ppm (low-dose), or 430 ppm (high-dose) of lead acetate via dams' milk from …

The Novel Characterization Of Extracellular Vesicles Containing Proteins Which Have Been Implicated In The Pathogenesis Of Hiv Associated Neurocognitive Disorders, Grace Ispas

Master's Theses

Although Anti-Retroviral Therapy (ART) is practiced, HIV-1 positive individuals still experience HIV-Associated Neurocognitive Disorders (HAND), collectively described as the presentation of neurocognitive, behavioral and motor dysfunctions that decrease the quality of life, while increasing the mortality in ART suppressed HIV-1 positive patients.

Current literature suggests that extracellular vesicles are involved in the pathogenesis of HAND as they are believed to be transferring HIV-1 proteins to nearby neuronal cells. Although most studies assume homogeneity among populations, characterizing cellular proteins or RNA levels in bulk, we hypothesize that distinct populations of extracellular vesicles are released and that environmental conditions, including viral infections, …

Dexamethasone Treatment Effects On H3k27me3 Chromatin Organization Is Related To Nk Cell Immune Dysregulation, Michael Sarafeno Misale

Master's Theses

It is well-established that psychological stress reduces natural killer (NK) cell immune function. This reduction is mediated by stress-induced release of glucocorticoids (GC), which can suppress immune function. Associated with suppression of a particular immune function are GC induced histone-epigenetic marks. Histone-epigenetic marks are responsible for the organization and compartmentalization of genomes into transcriptionally active euchromatin domains that are localized to the interior of the nucleus. Transcriptionally silent heterochromatic domains are enriched with methylated epigenetic marks and are localized to the nuclear periphery. The purpose of this investigation was to assess the influence of GC on H3K27me3 chromatin organization by …

Multifunctional Regulatory T Cells From Human Umbilical Cord Blood And The Role Of Tumor Necrosis Factor In Immune Homeostasis, Alexander Nelson

Master's Theses

Regulatory T cells (Tregs) are required to suppress inflammation and prevent autoimmunity. During fetal development Tregs are crucial to maintain tolerance between mother and child. After birth, neonates require tolerance to avoid harmful immune responses to foreign antigens in food and allow colonization with commensal microbes. We demonstrate a propensity for T cells in human umbilical cord blood to differentiate into Tregs in response to antigen receptor stimulation ex vivo. Cord blood-derived Tregs potently suppress T cell proliferation, but also produce pro-inflammatory cytokines known to activate innate immune responses. These results suggest that antigen exposure during early life results in …

A Presence-Only Species Distribution Model Comparison Predicting The Distribution Of The Amphibian Chytrid Fungus (Batrachochytrium Dendrobatidis), Melanie L. Torres

Murray State Theses and Dissertations

Global anthropogenic impacts have incited devastating effects on both human and wildlife populations. Emerging infectious diseases (EID) are one consequence of these impacts. One particular EID, chytridiomycosis, is a threat to global amphibian populations, causing massive die-offs and several species extinctions. While predictive modeling has helped the general understanding of where the aquatic pathogen causing chytridiomycosis, Batrachochytrium dendrobatidis (Bd), could spread to, most models are on continental or countrywide scales. This coarse-scale modeling makes local management and conservation planning for imperiled amphibians difficult. In addition, modeling efforts can vary depending on location and species, making it necessary to test the …

Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser

Theses and Dissertations (Comprehensive)

Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed …

Disease Models With Immigration, Reem Almarashi

Theses and Dissertations (Comprehensive)

In this thesis we focus first on studying the susceptible, exposed, and infected ($SEI$) disease model without immigration. We determine the basic reproduction number $\mathcal{R}_0$, which can be interpreted as the expected number of new cases that can be produced by a single infection in a completely susceptible population. Further, by using the Jacobian matrix, we determine the local stability of the disease model. Then we have the result that when $\mathcal{R}_0<1$ the DFE point is locally asymptotically stable(L.A.S). In contrast, when $\mathcal{R}_0>1$ we find that the endemic equilibrium is L.A.S. After that, we analyze the $SEI$ model with immigration of infected individuals.

Furthermore, we investigate the direction that the …

Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape

Theses and Dissertations

Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …

Vaccination Status And Factors For Non- Vaccination In Children At A Tertiary Care Hospital, Shiyam Sunder Tikmani, Tufail Soomro, Sumera Aziz Ali

Community Health Sciences

Immunization is a very effective strategy to prevent against common infectious disease. The objectives of the study were to determine the immunization status and reasons for non-vaccination of children coming to Civil Hospital Sukkur. This cross-sectional study was conducted pediatric OPD at Civil Hospital Sukkur from January 1, 2013, to June 30, 2013. Parents of children under five years of age brought their child to Outpatient Department of Civil Hospital Sukkur for any illness were asked to participate in the study. Parents who gave informed consent were included in the study. Data were collected using a small questionnaire by the …

Pseudopecoelus Mccauleyi N. Sp. And Podocotyle Sp. (Digenea: Opecoelidae) From The Deep Waters Off Oregon And British Columbia With An Updated Key To The Species Of Pseudopecoelus Von Wicklen, 1946 And Checklist Of Parasites From Lycodes Cortezianus (Perciformes: Zoarcidae), Charles K. Blend, Norman O. Dronen, Gábor R. Rácz, Scott Lyell Gardner

Scott L. Gardner Publications

Pseudopecoelus mccauleyi n. sp. (Opecoelidae: Opecoelinae) is described from the intestine of the bigfin eelpout, Lycodes cortezianus (Gilbert, 1890) (Perciformes: Zoarcidae), collected at 200–800 m depths in the northeastern Pacific Ocean off Oregon and Vancouver Island, British Columbia. The new species is distinguished by possessing a unique combination of the following diagnostic characters: vitelline fields that extend to the posterior margin of the ventral sucker; a slender, tubular and sinuous seminal vesicle that extends some distance into the hindbody; an unspecialized, protuberant ventral sucker; a genital pore at pharynx level; lobed to deeply multilobed testes; a lobed ovary; and an …

A New Species Of Catenotaenia (Cestoda: Catenotaeniidae) From Pygeretmus Pumilio Kerr, 1792 From The Gobi Of Mongolia, Altangerel Tsogtsaikhan Dursahinhan, Batsaikhan Nyamsuren, Danielle Marie Tufts, Scott Lyell Gardner

Scott L. Gardner Publications

From 1999 through 2012, a total of 541 individual rodents (jerboas of the family Dipodidae) were collected from several habitat types, primarily from the Gobi region of Mongolia, and were examined for helminth and protistan parasites. Of those rodents, 25 were identified as Pygeretmus pumilio Kerr, 1792 (Rodentia: Dipodidae), whereas 516 were other species of jerboa from the provinces of Dornogobi, Dundgobi, Omnogobi, Ovorhangai, Bayanhongor, Gobi Altai, and Hovd. During our field work, we collected several cestodes; some of which represented undescribed species, and these new species occurred in 40% of P. pumilio from four separate collecting localities. We designate …

Development And Characterization Of Histidine-Tagged Hpv16 L2 And Ms2-Arginine-Tagged Recombinant Proteins For Downstream Processes, Tahiyat Alothaim

Dissertations, Master's Theses and Master's Reports

Human papillomaviruses (HPVs) are the most common sexually transmitted infections. Persistent infection with HPV can lead to anogenital cancers including head and neck cancers. Three prophylactic vaccines have been approved to prevent against some types of HPV infection. However, the vaccines are HPV-type specific and protect mostly against the HPV types included in the vaccines. To offer broader protection against more HPV types, studies in the field are developing candidate vaccines targeting a conserved minor capsid protein, L2. Nevertheless, reagents for developing and assessing L2 vaccines are limited. For example, antibodies to assess the antigenicity of some L2 epitopes are …

Rapid Typing Of Mannheimia Haemolytica Major Genotypes 1 And 2 Using Maldi-Tof Mass Spectrometry, John Dustin Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories.

Cytolytic Toxin Production By Staphylococcus Aureus Is Dependent Upon The Activity Of The Protoheme Ix Farnesyltransferase, Emily Stevens, Maisem Laabei, Stewart Gardner, Greg A. Somerville, Ruth C. Massey

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use …

Branched Chain Α-Ketoacid Dehydrogenase Kinase 111–130, A T Cell Epitope That Induces Both Autoimmune Myocarditis And Hepatitis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A. Uzal, Jennifer L. Strande, Gustavo A. Delhon, Jean-Jack Riethoven, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread.

Methods: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKD_k) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.

Results: We demonstrate that BCKD_k protein contains at least nine immunodominant epitopes, three of which, BCKD_k 71–90, BCKD_k 111–130 and BCKD_k 141–160, …

Mechanistic Understanding Of N-Glycosylation In Ebola Virus Glycoprotein Maturation And Function, Bin Wang, Yujie Wang, Dylan A. Frabutt, Xihe Zhang, Xiaoyu Yao, Dan Hu, Zhuo Zhang, Chaonan Liu, Shimin Zheng, Shi-Hua Xiang, Yong-Hui Zheng

School of Veterinary and Biomedical Sciences: Faculty Publications

The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP₁ and the fusion-mediating GP₂ subunits and incorporated into virions to initiate infection. GP₁ and GP₂ form heterodimers that have 15 or two N-glycosylation sites (NGSs), respectively. Here we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that, although GP₁ NGSs are not critical, the two GP₂ NGSs, Asn⁵⁶³ and Asn⁶¹⁸, are essential for GP function. Further analysis uncovered that Asn⁵⁶³ and Asn^{618 …}

A Novel Role Of Silibinin As A Putative Epigenetic Modulator In Human Prostate Carcinoma, Ioannis Anestopoulos, Aristeidis P. Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I. Panayiotidis, David J. Kroll, Aglaia Pappa

School of Veterinary and Biomedical Sciences: Faculty Publications

Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, …

Ccpa Affects Infectivity Of Staphylococcus Aureus In A Hyperglycemic Environment, Markus Bischoff, Bodo Wonnenberg, Nadine Nippe, Naja J. Nyffenegger-Jann, Meike Voss, Christoph Beisswenger, Cord Sunderkotter, Virginie Molle, Quoc Thai Dinh, Frank Lammert, Robert Bals, Mathias Herrmann, Greg A. Somerville, Thomas Tschernig, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S. aureus suggests it may be important for infections in hyperglycemic individuals. To test this suggestion, hyperglycemic non-obese diabetic (NOD; blood glucose level ≥20 mM) mice were challenged with the …

Pseudoscorpions Of The Family Cheiridiidae (Arachnida: Pseudoscorpiones) Recovered From Burial Sediments At Pachacamac (500–1,500ce), Peru, Johnica J. Morrow, Livia Taylor, Lauren Peck, Christian Elowsky, Lawrence Stewart Owens, Peter Eeckout, Karl Reinhard

Karl Reinhard Publications

Fragmented remains of pseudoscorpions belonging to the family Cheiridiidae (Arachnida, Pseudoscorpiones) were recovered from Ychsma polity (c. AD 1000–1475) burial sediments from Pachacamac, Peru. Sediments from 21 burials were examined following rehydration in 0.5% trisodium phosphate for 48 h and subsequent screening through a 250 lm mesh. Materials larger than 250 lm were surveyed for the presence of arthropods. A total of two samples contained pseudoscorpion fragments, which were collected and quantified to determine the minimal number of pseudoscorpions present per gram of each sample. Following quantification, pseudoscorpion specimens were imaged utilizing confocal laser scanning microscopy (CLSM) to assist with …

Role Of The Interleukin-22 And Stat3 Signaling Pathway In Gut Barrier Maintenance Following Intoxication And Burn Injury, Adam M. Hammer

Dissertations

More than half of patients admitted to burn centers for treatment have measurable alcohol levels in their blood. Intoxication that precedes a traumatic burn injury leads to worsened patient outcomes, including higher rates of infection and sepsis. The intestines harbor the largest concentration of bacteria in the human host. Any disruption of the intestinal barrier as a result of intoxication and burn injury could contribute to infection and/or sepsis from gut-derived microbes. Previous work has demonstrated that the intestinal barrier becomes leaky, and that administration of interleukin-22 (IL-22) significantly reduces gut barrier leakiness following alcohol and burn injury. However, the …