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Berlin Brandenburg

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  • 11
    Dissertation
    Dissertation
    Language: English
    Description: Thesis (Ph. D.)--University of Wisconsin--Madison, 1996. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
    Source: Networked Digital Library of Theses and Dissertations
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  • 12
    Description: Indiana University-Purdue University Indianapolis (IUPUI) Lyme disease, the most prevalent vector-borne illness in the United States, is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (Bb). This spirochete is maintained in nature through an enzootic cycle involving ticks and small mammals. The Bb genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection. One of these lipoproteins is the major outer surface protein C (OspC) whose production is induced during transmission as spirochetes transition from ticks to mammals. OspC is required for Bb to establish infection in mice and has been proposed to facilitate evasion of innate immunity. However, the exact biological function of OspC remains elusive. Our studies show the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement, whereas the wild-type spirochete was fully infectious in these mice. The ospC mutant also could not establish infection in SCID and C3H mice that were transiently neutropenic during the first 48 h post-challenge. However, depletion of F4/80+ phagocytes at the skin-site of inoculation in SCID mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted SCID mice, the ospC mutant was capable to colonize the joints and triggered neutrophilia during dissemination in a similar pattern as wild-type bacteria. We then constructed GFP-expressing Bb strains to evaluate the interaction of the ospC mutant with phagocytes. Using flow cytometry and fluorometric assay for phagocytosis, we found that phagocytosis of GFP-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 cells was significantly higher than parental wild-type Bb strains, suggesting that OspC has an anti-phagocytic property. This enhancement in phagocytosis was not mediated by MARCO and CD36 scavenger receptors and was not associated with changes in mRNA levels of TNFα, IL-1β, and IL-10. Phagocytosis assays with HL60 neutrophil-like cells showed that uptake of Bb strains was independent to OspC. Together, our findings reveal that F4/80+ phagocytes are important for clearance of the ospC mutant, and suggest that OspC promotes spirochetes' evasion of macrophages in the skin of mice during early Lyme borreliosis.
    Keywords: Borrelia Burgdorferi ; Ef-Tu ; Infection ; Lyme Disease ; Ospc ; Phagocytes ; Lyme Disease ; Borrelia Burgdorferi -- Research ; Protein C ; Lyme Disease -- Molecular Aspects ; Relapsing Fever ; Spirochetes -- Molecular Aspects ; Bacteria
    Source: Networked Digital Library of Theses and Dissertations
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  • 13
    Description: Indiana University-Purdue University Indianapolis (IUPUI) Toxoplasma gondii, a single-celled eukaryotic pathogen, has infected one-third of the world’s population and is the causative agent of toxoplasmosis. The disease primarily affects immunocompromised individuals such as AIDS, cancer, and transplant patients. The parasites can infect any nucleated cell in warm-blooded vertebrates, but because they preferentially target CNS, heart, and ocular tissue, manifestations of infection often include encephalitis, myocarditis, and a host of neurological and ocular disorders. Toxoplasma can also be transmitted congenitally by a mother who becomes infected for the first time during pregnancy, which may result in spontaneous abortion or birth defects in the child. Unfortunately, the therapy currently available for treating toxoplasmosis exhibits serious side effects and can cause severe allergic reactions. Therefore, there is a desperate need to identify novel drug targets for developing more effective, less toxic treatments. The regulation of proteins via lysine acetylation, a reversible post-translational modification, has previously been validated as a promising avenue for drug development. Lysine acetyltransferases (KATs) are responsible for the acetylation of hundreds of proteins throughout prokaryotic and eukaryotic cells. In Toxoplasma, we identified a KAT that exhibits homology to Elongator protein 3 (TgElp3), the catalytic component of a transcriptional elongation complex. TgElp3 contains the highly conserved radical S-adenosylmethionine and KAT domains but also possesses a unique C-terminal transmembrane domain (TMD). Interestingly, we found that the TMD anchors TgElp3 in the outer mitochondrial membrane (OMM) such that the catalytic domains are oriented towards the cytosol. Our results uncovered the first tail-anchored mitochondrial KAT reported for any species to date. We also discovered a shortened form of Elp3 present in mouse mitochondria, suggesting that Elp3 functions beyond transcriptional elongation across eukaryotes. Furthermore, we established that TgElp3 is essential for parasite viability and that its OMM localization is important for its function, highlighting its value as a potential target for future drug development.
    Keywords: Lysine Acetyltransferase ; Toxoplasma Gondii ; Mitochondria ; Toxoplasma Gondii -- Research -- Analysis ; Toxoplasmosis ; Immunosuppression ; Parasites -- Physiology ; Parasitic Diseases -- Immunological Aspects ; Lysine ; Cellular Signal Transduction ; Acetylation ; Acetyltransferases ; Eukaryotic Cells ; Prokaryotes ; Virulence (Microbiology) -- Genetic Aspects ; Mitochondria ; Membranes (Biology) ; Immune Response -- Regulation ; Post-Translational Modification
    Source: Networked Digital Library of Theses and Dissertations
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  • 14
    Description: Indiana University-Purdue University Indianapolis (IUPUI) Pseudomonas aeruginosa is a gram negative opportunistic pathogen with the capacity to cause serious disease by forming biofilms, most notably in the lungs of cystic fibrosis (CF) patients. Biofilms are communities of microorganisms that adhere to a solid surface, undergo global regulatory changes, secrete exopolysaccharides, and are innately antibiotic resistant. Virulence modulation is an important tool utilized by P. aeruginosa to propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified including the protein, MgtE. MgtE has recently been discovered and has been implicated in virulence modulation, as an isogeneic mutation of mgtE leads to increased cytotoxicity. To further elucidate the role of MgtE in P. aerugionsa infections, transcriptional and translational regulation of this protein following antibiotic treatment has been explored. I have demonstrated that mgtE is transcriptionally upregulated following antibiotic treatment of most of the twelve antibiotics tested utilizing RT-PCR and QRT-PCR. A novel model system was employed, which utilizes cystic fibrosis bronchial epithelial (CFBE) cells homozygous for the ΔF508 mutation for these studies. This model system allows P. aeruginosa biofilms to form on CFBE cells modeling the P. aeruginosa in the CF airway. Translational effects of antibiotic treatment on MgtE have been attempted via Western blotting and cytotoxicity assays. Furthermore, to explore the possibility that mgtE is interacting with a known regulatory pathway, a transposon-mutant library was utilized and the regulatory proteins, AlgR and NarX, among others have been identified as possibly interacting with MgtE. Lastly, an MgtE homologue from Staphylococcus aureus was utilized to further demonstrate the virulence modulatory effects of MgtE by demonstrating the expression of the homologue results in decreased cytotoxicity, exactly like expression of the native P. aeruginosa MgtE. This research explores a newly discovered protein that impacts cytotoxicity and biofilm formation and provides valuable information about P. aeruginosa virulence.
    Keywords: Pseudomonas Aeruginosa ; Biofilm ; Cfbe Cell ; Algr ; Mgte ; Co-Culture ; Virulence ; Biofilms ; Pathogenic Microorganisms ; Bacteria -- Physiology ; Antibiotics -- Immunology ; Microbial Toxins ; Virulence (Microbiology) ; Cystic Fibrosis ; Pseudomonas Aeruginosa Infections -- Pathogenesis ; Pseudomonas Aeruginosa Infections -- Treatment ; Staphylococcus Aureus
    Source: Networked Digital Library of Theses and Dissertations
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  • 15
    Description: The US-Mexico border divides the communities of Palomas, Chihuahua and Columbus, New Mexico, but they remain intimately linked. Both communities suffer from inadequate social services, poor public infrastructure, high unemployment and high poverty rates. To confront these challenges, Palomas and Columbus work together, sharing resources like hospitals, firefighters, and even schools. Palomas and Columbus also share another vital resource—groundwater. In the parched Chihuahuan desert, the communities depend on this groundwater as their sole water supply source, yet their aquifer is contaminated with arsenic and fluoride. Local governments acknowledged this contamination as early as the 1970s, but it was not until the 2000s that they received the needed reverse osmosis technology and water/wastewater infrastructure to ameliorate household exposure to water contamination. This thesis compares how Columbus and Palomas have addressed water insecurity over a twenty-year period from 1996-2016, using a 1996 study as the baseline (Tanski et al. 1998). New data include a household survey of 152 households, 60 semi-structured interviews, and participant observations of water practices collected during two months of fieldwork in the summer of 2016. The central research questions of this thesis are Q1) What causes household water insecurity on the US-Mexico border? and Q2) How can water policymakers and providers more equitably provide users with access to clean, reliable, and affordable drinking water? From a human development perspective, water security is defined as having an adequate supply of reliable and affordable water for a healthy life. This thesis uses a political ecological lens to more critically examine how water security connects to socio-political processes of water governance and power imbalances. Following Jepson (2014), this thesis argues that water (in)security is produced by problems in water access, water quality, and water affect (or water distress) and unfolds within a complex, hydrosocial landscape. Applying Jepson’s (2014) water security typology to Columbus and Palomas revealed that each local water utility adopted a distinct approach to addressing groundwater contamination, predicated on their financial and social resources, and structured by national and bi-national water policies as well as their institutional parameters. The survey found household water security has improved in terms of water access and reliability. But, centralized water filtration technology increased costs and reduced affordability in Columbus, while decentralized water filtration technology inadequately resolved household water supply contamination in Palomas. Thus, despite the technological improvements, households remain unevenly exposed to water contamination and costs. This raises concern about approaches to water security, which should be more finely attuned to water equity. Water equity means the rights to access clean water are more equitably distributed within the communities, and there is greater recognition/participation of community members in decision making on water management.
    Keywords: Borderlands ; Contamination ; Transboundary Aquifer ; Water Equity ; Water Policy ; Water Security
    Source: Networked Digital Library of Theses and Dissertations
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  • 16
    Language: English
    Description: The urban/peri-urban phenomenon is frequently studied as a territorial landscape for urban expansion, and a good deal of scholarship chronicles aspects of land annexation, housing construction, and infrastructure. But the question of how peri-urban water resources have been reallocated to serve urban needs has not received sufficient scholarly attention. Peri-urban water reallocation demands examination in arid regions where water is a critical resource. Mexico's northwest region represents one of the most critical examples; the most-drought prone region in Mexico, it is characterized by over-drafted groundwater sources and rapid urban growth. In this research, based on the case of Hermosillo, Sonora, I develop three distinct, yet related themes to examine the peri-urban phenomenon.First, this work draws on the notion of the "hydrosocial cycle" (Swyngedouw, 2004) to examine geographies of power at the urban-rural interface. Following Swyngedouw, we argue that urban water augmentation strategies reveal a distinct set of urban-rural relations of uneven social power where peri-urban water resources are "metabolized" in urban areas, reflecting the demands of powerful, politically connected urban individuals and populations over more disparate and marginalized rural producers. The Hermosillo case indicates that small-scale farming communities or ejidos are the most vulnerable water users because of their lack of political power in the governmental decision making process.Second, in this work, I examine how peri-urban rural livelihoods have been reshaped by cities' water reallocation causing ejidatarios in many cases to lose their livelihoods, but without creating new urban jobs as an alternative means of subsistence, resulting in a net negative outcome for ejido members.Finally, this research evaluates the land use/cover change dynamics and their effects in the peri-urban area of the city of Hermosillo. This study demonstrates that urban expansion causes at least two other types of land use/cover changes (LUCC) beyond the urban fringe that are not usually considered in LUCC studies. The research demonstrates that urban expansion in the peri-urban land is a broader and more complex phenomenon than previously understood and examines how water transfers act as a driver of land use/cover change.
    Keywords: Geography ; Land ; Livelihoods ; Mexico ; Peri-Urban ; Water
    Source: Networked Digital Library of Theses and Dissertations
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  • 17
    Dissertation
    Dissertation
    Oklahoma State University
    Description: Curriculum and Instruction
    Source: University of Oklahoma/Oklahoma State University
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  • 18
    Description: Curriculum and Instruction
    Source: University of Oklahoma/Oklahoma State University
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  • 19
    Description: Curriculum and Instruction
    Source: University of Oklahoma/Oklahoma State University
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  • 20
    Description: This study was an observation of teachers as they attempted to employ innovative practices in their respective classrooms. These practices were strategies used by whole language practitioners who claim that their educational philosophy represents a major paradigm shift in education. It was found that, while several innovative strategies were being used in these whole language classrooms, direct instruction continued to be the teaching model most commonly used. Additionally, only 25 percent of the participants stated that they read aloud regularly to their classes although the significance of reading aloud has been established as incontrovertible. Enthusiasm of students was a very positive factor in effecting change; whereas, mandates from higher levels tended to be met with resistance. The lack of a clearly-defined philosophical base was manifested in the discrepancy between many classroom practices and the whole language philosophy. Although whole language is diefined as a philosophy, none of those whole language neophytes used this term in their definition of whole language. The results suggest that, before a teacher can successfully make the transition from a traditional teacher to a whole language teacher, one needs time and encouragement to reflect upon one's beliefs and practices. It is also believed that it is possible to initiate a transition by first utilizing whole language teaching strategies, and then gradually making the philosophical shift.
    Description: Curriculum and Instruction
    Source: University of Oklahoma/Oklahoma State University
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