Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
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.
Browse
10 results
Search Results
Item INFLAMMATORY MACROPHAGE REGULATION OF ANGIOGENESIS AND SKELETAL MUSCLE PHENOTYPES(2023) Evans, William Stuart; Prior, Steven J; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chronic inflammation is a hallmark of cardiovascular disease; however, there is a lack of understanding of how systemic inflammation affects the peripheral skeletal muscle to potentially hasten frailty and functional declines in patients. The overarching objective of this dissertation was to determine whether this systemic inflammation is accompanied by macrophage infiltration of skeletal muscle and reductions in skeletal muscle capillarization and fiber size. Using animal models of a) heart failure (HF) induced by transverse aortic constriction (TAC), and b) skeletal muscle ischemia, this work illuminates changes that occur in skeletal muscle with cardiovascular disease-related inflammation. The first study demonstrated that pressure overload resulted in cardiac hypertrophy in male rats consistent with heart failure with preserved ejection fraction (HFpEF), while females did not show cardiac hypertrophy or HF. The second study demonstrated sex-specific differences in skeletal muscle, with TAC male rats exhibiting smaller fiber sizes and greater capillarization, and female TAC rats exhibiting lower capillarization than Sham counterparts. This study then investigated skeletal muscle macrophages to determine whether they might underly or contribute to these differences. There were fewer macrophages in the skeletal muscle of male TAC rats than male Sham rats, and macrophage conditioned medium from TAC rats produced less-developed capillary networks in an ex vivo, experimental assay. Finally, the third study investigated whether an acute bout of systemic inflammation, in the absence of HF, could alter the infiltration of macrophages, or skeletal muscle fiber size or capillarization. Hindlimb ischemia was used to induce acute, systemic inflammation that peaked after 1 day. This systemic inflammation increased the infiltration of macrophages into remote, non-ischemic skeletal muscle by day 7; however, muscle structure was preserved over this short time course. This dissertation demonstrates that cardiovascular disease-associated inflammation is linked with tissue-level changes in macrophages in a sex-specific manner. These changes accompany and may, over time, contribute to skeletal muscle fiber atrophy and changes in capillarization in cardiovascular disease patients.Item SPRAY STRATEGIES AND SELECTION FOR FUNGICIDE RESISTANCE: FENHEXAMID RESISTANCE IN BOTRYTIS CINEREA AS A CASE STUDY(2023) Boushell, Stephen Carl; Hu, Mengjun; Plant Science and Landscape Architecture (PSLA); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Fungicide resistance is a limiting factor in sustainable crop production. Despite the wide adoption of general resistance management strategies by growers, the recent rate of resistance development in important fungal pathogens is concerning. In this study, Botrytis cinerea and the high-risk fungicide fenhexamid were used to determine the effects of fungicide dose, tank mixture, and application timing on resistance selection across varied frequencies of resistance via both detached fruit assays and greenhouse trials. The results showed that application of doses lower than the fungicide label dose, mixture with the low-risk fungicide captan, and application post-infection seem to be the most effective management strategies in our experimental settings. In addition, even a small resistant B. cinerea population can lead to a dramatic reduction of disease control efficacy. Our findings were largely consistent with the recent modeling studies which favored the use of the lowest possible fungicide dose for improved resistance management.Item STRUCTURE-FUNCTION ANALYSES OF AN ESSENTIAL VIRULENCE DETERMINANT OF THE LYME DISEASE PATHOGEN(2022) Foor, Shelby Dimity; Pal, Utpal; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Lyme Disease (LD) is a tick-borne disease caused by a group of gram-negative-like spirochetal pathogens called Borrelia burgdorferi sensu lato. The number of cases reported in the United States have dramatically increased with CDC estimating 476,000 cases annually. This multifaceted infection can spread throughout the entire body, causing clinical complications of the central nervous system, joint and heart. Early antibiotic treatment is available and effective; however, untreated patients can develop chronic symptoms, and even after antibiotics, symptoms of unknown etiology and pathogenesis can develop into post-treatment Lyme disease syndrome (PTLDS). The enzootic life cycle of B. burgdorferi is maintained typically between a small rodent and the Ixodes tick vector, where transmission occurs during tick feeding on a host. Infection establishes after B. burgdorferi is deposited in the dermis and undergoes the required shift in its protein expression profile necessary to support spirochete persistence and pathology, often highlighting protein targets for development of diagnostic, therapeutic, and preventative measures. Two such proteins identified, BB0238 and BB0323, serve as novel virulence determinants and are essential for mammalian infection. These two proteins directly interact, mutually stabilize each other post-translationally, and form an essential complex required for infection; however, their precise functions remain undetermined. In collaborative efforts, we predicted a two-domain structure of BB0238. The N-terminal domain was predicted by AI methods to harbor an antiparallel helix-turn-helix motif (HTH) followed by a third helix and a low-confidence predicted meandering segment. The C-terminal domain structure was determined by X-ray crystallography as well as predicted with high confidence to adopt an α+β fold that resembles closely that of the nuclear transport factor 2 (NTF2) superfamily. While full-length BB0238 lacks homology to singular proteins of known functions, the individual N- and C-terminal regions display structural homology to non-bacterial proteins, particularly to eukaryotic sorting, or transport proteins, suggesting that BB0238 supports an unconventional function in spirochetes. We discovered that BB0238 binds another borrelial protein annotated as BB0108, orthologs of two bacterial chaperones and foldases, the extracellular membrane anchored PrsA, and the periplasmic SurA. This identified interaction requires further investigation, however, may be important for BB0238 protein stability or assist with the novel BB0238 function discovered herein, which regulates proteolytic processing of BB0323. Furthermore, We show that key amino acid residues within the HTH stabilize BB0238 in an environment-specific manner, influence its oligomerization properties, and facilitate tick-to-mouse transmission by aiding spirochete evasion of host cellular immunity, underscoring BB0238’s ability to support microbial establishment during early mammalian infection. Together, these studies highlight the divergent evolution of multidomain spirochete proteins involved in multiplex protein-protein interactions, possibly facilitating multiple functions, which support pathogen survival and thus, represent novel targets for vaccine and therapeutic development against Lyme disease.Item PATHOLOGICAL PREGNANCIES: THE TRUMP ADMINISTRATION’S ASSAULT ON MIGRANT WOMEN’S REPRODUCTIVE HEALTH AND HOW BROWN WOMEN ACTIVISTS SPOKE BACK TO POWER(2022) de Saint Felix, Skye; Parry-Giles, Shawn J.; Communication; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Abortion and immigration are two polarizing political issues in the United States. These issues were made more contentious under the Trump administration (2017-2021) that tapped into cultural and historical memories of abortion as a pathological practice. Situated at the intersection of abortion and immigration rights, migrant women’s reproduction was treated as something to be monitored and controlled to preserve white patriarchal interests. The Trump administration capitalized on the racist and sexist tenets inherent to rhetorical pathology to construct an enemy in migrant women that only his administration was qualified to neutralize through deportation, arrest, and extreme legislation. Rhetorical pathology, in the context of anti-abortion and anti-migrant policies, resulted in contradictory commitments. For instance, the Trump administration and his supporters at once humanized the fetus, but dehumanized Brown women and children by blocking them from entering the country and accessing basic needs. Administrative officials also argued that their anti-abortion platform prevented racial genocide by saving Black and Brown babies while they treated them as enemy threats to be purged from the country. I ultimately argue that white supremacy and patriarchy are unifying ideologies in rhetorical pathology that help these contradictions “make sense” for Trump supporters and anti-abortion groups. In Chapter One, I examine the Trump administration’s efforts to force birth and block paths to citizenship for migrant girls by studying the case of Jane Doe and the abuses she faced in the Office of Refugee Resettlement Custody (ORR). In Chapter Two, I investigate how white supremacists and misogynists co-opted progressive rhetoric to undermine its force by analyzing Trump’s policies that heavily regulated migrant women’s reproduction. Such cruel and unconscionable actions included reinstating (and expanding) the Global Gag Rule and passing “conscience” legislation that allows healthcare providers to discriminate against healthcare they deem “immoral” like abortion care or emergency contraceptives. In this chapter, we also see how conservatives inverted progressive frames like “Black Lives Matter” to argue that “Babies Lives Matter” to fulfill an anti-choice agenda and describe themselves as abolitionists and saviors of Brown children. In Chapter Three, I show the ways in which Brown women activists reappropriated the rhetorical power that conservatives mimicked to justify their inhumane policies. Activist women reclaimed their rhetorical power of definition, shared stories of both horror and community uplift, and used rhetorical secrecy to combat rhetorical pathologizations. Legislation in support of migrant women emphasized healing and care to undermine the rhetorics of pathology. This project ultimately exposes how rhetorical pathology operates in order to neutralize its power and center the voices and experiences of migrant women in abortion and immigration debates.Item NEISSERIA GONORRHOEAE MODULATES INFECTIVITY BASED ON PROPERTIES OF HUMAN CERVICAL EPITHELIA AND PHASE VARIABLE BACTERIAL SURFACE STRUCTURES(2019) Yu, Qian; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Neisseria gonorrhoeae (GC) infection in the human female reproductive tract causes various clinical outcomes, from no symptom to severe complications. The major barrier to a better understanding of GC infection in women is the lack of experimental system closely mimicking in vivo infection. Here, I developed a human cervical tissue explant model, which maintains the heterogeneity of the cervical epithelium. Using this model, my thesis research examined the impact of the heterogeneity of the cervical epithelium and the phase variation of GC surface structures on GC infectivity. My research revealed that GC preferentially colonize the ectocervix and the transformation zone (TZ), but exclusively penetrate into the subepithelial tissues of the TZ and endocervix. Pili are essential for GC colonization in all regions of the cervix. Expression of Opa isoforms that bind to the host receptors CEACAM (OpaCEA) enhances GC colonization in the ecto/endocervix but inhibits GC penetration into the endocervix. However, GC infectivity in the TZ does not respond to Opa phase variation, due to the low expression level and intracellular location of CEACAMs in the TZ epithelial cells. OpaCEA enhances GC colonization in the ecto/endocervix by inhibiting epithelial exfoliation and suppresses GC penetration into the endocervical subepithelium by inhibiting GC-induced disassembly of the apical junction. Opa-mediated modulation of GC infectivity depends on the immune receptor tyrosine-based inhibitory motif (ITIM) of CEACAM1 and its downstream phosphatase SHP. The effect of epithelial cell polarity on GC invasion was studied using a cell line model. My results show that GC invade more efficiently into non-polarized than polarized epithelial cells without changing the adhesion efficiency. Opa (phase variable) expression enhances both adhesion and invasion in both non-polarized and polarized cells. In non-polarized cells, Opa expression induces F-actin accumulation and microvilli elongation underneath GC microcolonies, suggesting an actin-mediated uptake of GC. In contrast, GC expressing no Opa reduce F-actin and demolish microvilli underneath microcolonies in both polarized epithelial cell line and endocervical epithelial cells potentially by increasing calcium flux, NMII activation and the redistribution of actin nucleation factor Arp2/3 from the apical surface. Taking together, my research demonstrates that both the heterogeneity of the cervical epithelium and the phase variation of bacterial surface structures regulate GC infectivity in the human cervix, either dominated by colonization or penetration, consequently influencing the clinical outcomes of the infection.Item The immunoregulation of interleukin-27 in African trypanosome infection(2018) Liu, Gongguan; Shi, Meiqing; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Interleukin (IL)-27 is a cytokine with diverse impacts on regulation of vertebrate T helper Type 1 (Th1) responses. Initially, it was predicted as a promoter of Th1 responses. However, it was lately identified as a potent negative regulator of T cell responses in a variety of disease models, including infection with viruses, bacteria, and intracellular parasites. The extracellular protozoan parasites, African trypanosomes, cause a chronic debilitating disease associated with persistent inflammation. Using this infection model, we aim to identify novel immunoregulatory functions of IL-27 on innate and adaptive immunity. Here we demonstrate that IL-27 receptor deficient (IL-27R-/-) mice infected with African trypanosomes display excessive production of IFN-γ by CD4+ T cells, exacerbated liver pathology, and dramatically shortened survival as compared with infected wild-type mice. Depletion of CD4+ T cells or neutralization of IFN-γ ameliorates the liver pathology and extends the survival of infected IL-27R-/- mice. Our further interest is in deciphering the mechanisms of how CD4+ T cells and IFN-γ shape the monocyte-featured innate immunity in African trypanosome infected IL-27R-/- mice. Blood monocytes typically consist of a heterogenous population of Ly6C+ and Ly6C- monocytes. Ly6C+ monocytes can give rise to inflammatory TNF-α/iNOS producing dendritic cells (Tip-DCs) and anti-inflammatory macrophages. Here we find that IL-27R-/- mice exhibit a higher frequency of Ly6C+ monocytes recruitment to the liver, where they preferentially differentiate into Tip-DCs. This is coincided with impaired development of Ly6C- monocytes and macrophages in the liver. Depletion of CD4+ T cells or neutralization of IFN-γ in infected IL-27R-/- mice diminishes the recruitment of Ly6C+ monocytes, and their differentiation into Tip-DCs in the liver. This is accompanied by the greatly enhanced counts of Ly6C- monocytes and macrophages following antibody treatments. Further evidences show that 1) IFN-γ produced by CD4+ T cells induces cell death of Ly6C- monocytes which perturb the development of Tip-DCs in infected IL-27R-/- mice and 2) cell intrinsic IFN-γ signaling drives Ly6C+ monocytes to differentiate into Tip-DCs in infected IL-27R-/- mice. Thus, our data identify IL-27 signaling as a novel immunoregulator to prevent Ly6C+ monocytes from differentiation into Tip-DCs through suppressing CD4+ T cells to secrete IFN-γ.Item EXPLORING IL-7R-ALPHA DEVELOPMENTAL EFFECTS AND ONCOGENIC COLLABORATIONS(2017) Cramer, Sarah Delia; Samal, Siba; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Acute lymphoblastic leukemia is the most common cancer of children. Individual cases of leukemia may have multiple genetic lesions, and identifying those that drive leukemogenesis will be important in the development of targeted therapy. Approximately 10% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) cases have a mutation in IL-7Rα. These mutations are thought to be oncogenic, but little is known about the effects of the mutation on T-cell development. In addition, the mutation does not seem to induce leukemia in the absence of other genetic lesions, suggesting that collaborative mutations are required for leukemogenesis. Based on patient data, potential collaborators include TLX3 expression, HOXA gene cluster overexpression, and NRAS mutation. Given the current state of knowledge regarding mutant IL-7Rα, this project was developed with two specific aims. The first was to investigate the effects of mutant IL-7Rα gain-of-function (IL-7Rα-GOF) on T-cell development in vitro and in vivo. The second was to determine whether candidate collaborative genetic lesions would drive T-ALL formation when combined with mutated IL-7Rα. To address these aims, immature murine thymocytes were cultured on an OP9-DL4 stromal cell system, transduced with retroviral vectors, and injected into sub-lethally irradiated Rag1-/- mice. Resultant diseases were analyzed using a variety of techniques including flow cytometry, histology, immunohistochemistry, ligation-mediated PCR, TCRβ clonality assessment, RNA-sequencing, serial passage, and limiting dilution assay. Studies showed that IL-7Rα-GOF mutation caused an increase of CD8+ cells in vitro. When thymocytes transduced with IL-7Rα-GOF mutation were injected into mice, animals developed a multi-systemic inflammatory disease. This inflammation was not due to imbalance in populations of Treg and Th17 cells, as had been hypothesized. Assessing collaborations with TLX3 expression, HOXA overexpression, and NRAS mutation showed that combination of these genetic lesions with IL-7Rα-GOF mutation caused different neoplastic diseases. The combination of IL-7Rα-GOF mutation and TLX3 expression caused low-penetrance, late-onset T-cell lymphoma. Thymocytes overexpressing the HOXA gene cluster and transduced with IL-7Rα-GOF mutation caused a rapid-onset myeloid leukemia. Combination of IL-7Rα-GOF mutation with mutant NRAS yielded rapid-onset, full-penetrance T-cell lymphoblastic leukemia, suggesting that this combination of mutations was sufficient to induce T-ALL. These experimental results may help to lay the foundation for the development of targeted therapy for pediatric T-ALL.Item UNDERSTANDING LATE SEASON FRUIT ROT PATHOSYSTEMS AND INSECT INTERACTIONS IN MID-ATLANTIC VINEYARDS(2016) Kepner, Cody; Swett, Cassandra L; Plant Science and Landscape Architecture (PSLA); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Fungal fruit rots and insect pests are among the most important problems negatively affecting the yield and quality of mid-Atlantic wine. In pathogenicity trials of fungi recovered from diseased Chardonnay and Vidal blanc grapes, Alternaria alternata, Pestalotiopsis telopeae, and Aspergillus japonicus were found to be unreported fruit rot pathogens in the region. Additionally, P. telopeae and A. japonicus had comparable virulence to the region’s common fruit rot pathogens. Furthermore, a timed-exclusion field study was implemented to evaluate vineyard insect-fruit rot relationships. It was found that clusters exposed to early-season insect communities that included Paralobesia viteana had a significantly greater incidence of sour rot than clusters protected from insects all season. These results were contrary to the current assumption that fall insects are the primary drivers of sour rot in the region. This research provides diagnostic tools and information to develop management-strategies against fungal and insect pests for mid-Atlantic grape growers.Item A microbiological study of torulosis(1949) Tawab, Salah Ahmed Abdel; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)Item The torsion of the humerus: Its site, cause and duration in man(1946) Krahl, Vernon E.; Digital Repository at the University of Maryland; University of Maryland (College Park, Md)