Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
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Item Immune Modulations of a Helminth Derived Protein(2023) Mekhemadhom Rajendrakumar, Arunraj; Zhu, Xiaoping XZ; Tuo, Wenbin WT; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The immune responses at the gastrointestinal mucosa modulate nematode parasite infection, initially characterized by the production of epithelium-derived, robust T helper 2 (Th2) type alarmin cytokines, such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Subsequently, the immune responses are mediated by releasing the lymphoid cell-derived Th2 immune cytokines, such as IL-13, IL-4, IL-5, IL-9, and parasite-specific antibodies. Studies have shown that parasitic nematode worms can establish a chronic infection in the intestine, even in a robust immune response. This evidence leads us to hypothesize that the nematode evolves to evade or regulate intestinal immunity through specific modulatory mechanisms that interfere with initial intestinal immune responses, allowing the nematode to survive. We used a model nematode, Heligmosomoides polygyrus bakeri (Hpb), to identify nematode-derived proteins with regulatory effects on Th2 immune cytokines during chronic infection. Through high throughput analysis, we found that a Hpb-derived protein could precisely modulate mouse immune response. The presence of the Hpb-derived protein was essential for the parasite's survival as the vaccine conferred a sterilizing immunity. As Th2 cytokines are directly associated with the pathogenesis of several inflammatory and autoimmune diseases, we are understanding how this protein regulates the function of the Th2 cytokines in vitro and in vivo and explore whether the protein could use to treat inflammatory diseases and serve as a vaccine target to control nematode infections.Item NOVEL ADAPTATIONS IN MORPHOLOGY, DEVELOPMENT, AND NUTRIENT AQUISITION FOR HOST EXPLOITATION IN THE MESOSTIGMATID HONEY BEE PARASITE VARROA DESTRUCTOR(2018) Ramsey, Samuel David; vanEngelsdorp, Dennis; Entomology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The parasitic mite Varroa destructor is the most significant single driver of the global honey bee health decline. Better understanding of the association of this parasite and its host is critical to developing sustainable management practices. This work shows that Varroa is not consuming hemolymph as has been the accepted view, but damages host bees by consuming fat body. Feeding wounds in adult bees were imaged for the first time showing that Varroa feed on the underside of the abdomen where fat body is the immediate underlying tissue. Fat body at the wound site showed evidence of external digestion. Hemolymph and fat body in honey bees were then marked with fluorescent biostains. Fluorescence associated with the fat body was consistently detected in the gut of mites fed on these bees while comparatively little fluorescence was detected from the hemolymph biostain. Mites were then fed a diet composed of one or both tissues. Mites fed fat body tissue survived longer and produced more eggs than those fed hemolymph. Mites fed hemolymph showed fitness metrics no different from the starved control group. Collectively, these findings show that Varroa are exploiting the fat body as their primary source of sustenance; a tissue integral to proper immune function, pesticide detoxification, overwinter survival and several other essential processes in healthy adult and immature bees. Additional study was undertaken to better understand how the Varroa accelerates its reproductive rate. Via gel electrophoresis and immunodetection, undigested honey bee vitellogenin was found in Varroa eggs. The presence and identity of these host proteins was confirmed via HPLC MS/MS. This particular cleavage of vitellogenin is found only in the fat body. These findings fundamentally alter our understanding of the etiology of varroosis and underscore a need to revisit our understanding of this parasite and its impacts, both direct and indirect, on honey bee health. Further study of Varroa adaptations focused on expanding knowledge of Varroa morphology with the aim of determining features that can distinguish between Varroa species. Using low temperature scanning electron microscopy, we were able to provide better resolution of key morphological features, detail variability within traits, and provide novel descriptions of certain characters.Item Meta-Transcriptomic Profiling of Human Cutaneous Leishmaniasis(2018) Christensen, Stephen Michael; Mosser, David M; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Our understanding of the spectral nature of the neglected tropical disease leishmaniasis, and of host-parasite interactions in general, remains incomplete. In this work, we used high throughput RNA-sequencing (RNA-seq) to analyze human host and Leishmania gene expression in cutaneous leishmaniasis patients. Skin biopsies were taken from a total of 25 localized cutaneous leishmaniasis (LCL), 6 diffuse cutaneous leishmaniasis (DCL), and 10 healthy patients. LCL separated into groups that lacked detectable parasite transcripts in lesions (PTNeg) and a group in which parasite transcripts were readily detected (PTPos). These groups exhibited substantial differences in host responses to infection, including B lymphocyte presence, B and T cell activation, and immunoglobulin production. Analysis of DCL lesions revealed distinct differences in host responses relative to LCL, including atypical B lymphocyte accumulation, diminished cytotoxic T lymphocyte responses, and an altered macrophage activation state. Surprisingly, neither localized nor diffuse forms of the disease could be correlated with any indication of a Th2 immune response that had previously been implicated in mouse models of L. major susceptibility. The presence of low levels of parasite transcripts in the majority of LCL patients made it difficult to obtain a comprehensive analysis of the parasite transcriptome in LCL. However, high levels of parasite transcripts in DCL afforded a unique opportunity to examine parasite gene expression in this disease. Despite differences in age, gender, and illness duration, there was a remarkable uniformity in parasite gene expression in all 6 DCL patients. We identified transcripts that were highly expressed by all 6 DCL patients, and then curated a subset of conserved genes highly expressed in multiple Leishmania species. These subsets of genes emerge as targets for further research on host-pathogen interactions and a better understanding of Leishmania infection.. In summary, RNA-seq allowed us to fully examine host and parasite transcriptomes, characterize host responses in localized and diffuse cutaneous leishmaniasis lesions, and determine factors that define the variations in disease manifestation. New approaches to modify host immune responses in this disease and new parasite targets for drug development may emerge from this work.Item Introductory study of the effect of enheptin (2-amino, 5-nitrothiazole) on the host-parasite relationship in blackhead(1953) Tromba, Francis Gabriel; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item Studies on identification and host-parasite relationships of the common root-knot nematodes (Meloidogyne spp.) with special reference to Maryland(1953) Sasser, J. N.; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item The effect of lysed Trypanosoma equiperdum preparations on blood sugar in the rat(1951) Piala, Joseph Joseph; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item A study of Trypanosoma equiperdum infection in the rat: With particular referene to blood sugar, erythrocytes, hemoglobin, platelets, plasma proteins and cause of death(1946) Hoppe, James Oliver; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item Diagnostic tests including hemotology in swine brucellosis and capsule formation in Brucella(1943) Cotton, Cornelia Marie; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item The host-parasite relationship in susceptible cantaloups, resistant cantaloups, and cucumbers inoculated with Fusarium bulbigenum (Cke. and Mass.) var. niveum Wr. f. 2(1943) Cox, Carroll Eastburn; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item CHARACTERIZATION OF HEME ACQUISITION IN LEISHMANIA(2014) Renberg, Rebecca; Andrews, Norma W; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Heme is an essential co-factor for many critical cellular processes. The protozoan parasite Leishmania amazonensis is a heme auxotroph and must acquire heme from the environment. One pathway of heme acquisition is through Leishmania Heme Response 1 (LHR1), a heme transporter localized to the plasma membrane and acidic intracellular compartments. In this work we further characterize LHR1 and the mechanism by which it promotes heme uptake. We show that overexpression of LHR1 in Leishmania amazonensis increases the total parasite intracellular heme pool, and that expression in Saccharomyces cerevisiae promotes uptake of the heme analog Zinc Mesoporphyrin IX (ZnMP). Our results indicate that heme binding to LHR1 is pH independent, whereas heme transport by the parasites is more efficient under acidic conditions. To examine the molecular mechanisms responsible for LHR1 heme transport, we performed a mutagenesis analysis of LHR1. We show that three key tyrosines residues, Tyr-18, Tyr-80, and Tyr-129, located in predicted transmembrane domains near the cytoplasmic leaflet of the plasma membrane, are important for heme transport. Although the mutant proteins appear to not affect promastigote growth, they have a profound inhibitory effect on intracellular amastigote replication in macrophages, and are necessary for virulence in vivo. Finally, we also examine the differential regulation of LHR1 expression in a visceralizing species, Leishmania chagasi, compared to L. amazonensis, a species that causes cutaneous lesions. L. chagasi has higher amounts of LHR1 transcripts than Leishmania amazonensis under heme-depleted conditions, and uptakes ZnMP faster and to a greater extent than Leishmania amazonensis. This differential regulation of LHR1 may be due to differences in the gene 3’ Untranslated Regions (UTRs) between the two species. This works adds to our understanding of the critical process of heme transport and its role in Leishmania virulence.