ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Throughout the Southwest, complex geology and physiography concomitant with climatic variability contribute to diverse stream hydrogeomorphologies. Many riparian plant species store their seeds in soil seed banks, and germinate in response to moisture pulses, but the climatic controls of this response are poorly understood. To better understand the ecological implications of a changing climate on riparian plant communities, I investigated seed bank responses to seasonal temperature patterns and to stream hydrogeomorphic type. I asked the following questions: Are there distinct suites of warm and cool temperature germinating species associated with Southwestern streams; how do they differ between riparian and terrestrial zones, and between ephemeral and perennial streams? How does alpha diversity of the soil seed bank differ between streams with ephemeral, intermittent, and perennial flow, and between montane and basin streams? Do streams with greater elevational change have higher riparian zone seed bank beta-diversity? Does nestedness or turnover contribute more to within stream beta-diversity?
I collected soil samples from the riparian and terrestrial zones of 21 sites, placing them in growth chambers at one of two temperature regimes, and monitoring emergence of seedlings for 12 weeks. Results showed an approximately equal number of warm and cool specialists in both riparian and terrestrials zones; generalists also were abundant, particularly in the riparian zone. The number of temperature specialists and generalists in the riparian zones did not differ significantly between perennial headwater and ephemeral stream types. In montane streams, alpha diversity of the soil seed bank was highest for ephemeral reaches; in basin streams the intermittent and perennial reaches had higher diversity. Spatial turnover was primarily responsible for within stream beta-diversity—reaches had different species assemblages. The large portion of temperature specialists found in riparian seed banks indicates that even with available moisture riparian zone plant community composition will likely be impacted by changing temperatures. However, the presence of so many temperature generalists in the riparian zones suggests that some component of the seed bank is adapted to variable conditions and might offer resilience in a changing climate. Study results confirm the importance of conserving multiple hydrogeomorphic reach types because they support unique species assemblages.
I collected soil samples from the riparian and terrestrial zones of 21 sites, placing them in growth chambers at one of two temperature regimes, and monitoring emergence of seedlings for 12 weeks. Results showed an approximately equal number of warm and cool specialists in both riparian and terrestrials zones; generalists also were abundant, particularly in the riparian zone. The number of temperature specialists and generalists in the riparian zones did not differ significantly between perennial headwater and ephemeral stream types. In montane streams, alpha diversity of the soil seed bank was highest for ephemeral reaches; in basin streams the intermittent and perennial reaches had higher diversity. Spatial turnover was primarily responsible for within stream beta-diversity—reaches had different species assemblages. The large portion of temperature specialists found in riparian seed banks indicates that even with available moisture riparian zone plant community composition will likely be impacted by changing temperatures. However, the presence of so many temperature generalists in the riparian zones suggests that some component of the seed bank is adapted to variable conditions and might offer resilience in a changing climate. Study results confirm the importance of conserving multiple hydrogeomorphic reach types because they support unique species assemblages.
ContributorsSetaro, Danika (Author) / Stromberg, Juliet (Thesis advisor) / Franklin, Janet (Committee member) / Makings, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2016
Description
Bouteloua eriopoda (Torr.) Torr., also known as black grama, is a perennial bunchgrass native to arid and semiarid ecosystems in the southwestern region of North America. As a result of anthropogenic climate change, this region is predicted to increase in aridity and experience more frequent extreme drought and extreme wet years. This change in precipitation will no doubt affect black grama; however, few studies have investigated how the specific structural components of this grass will respond. The purpose of this study was to examine the effects of years since start of treatment and annual precipitation amount on tiller and stolon densities, and to test for interaction between the two predictor variables. Additionally, the effects of annual precipitation on ramets and axillary buds were investigated. By using 36 experimental plots that have been receiving drought, irrigated, or control treatments since 2007, tiller density was the most responsive component to both annual precipitation amount and years since start of treatment. Years since start of treatment and annual precipitation amount also had a statistically significant interaction, meaning the effect of precipitation amount on tiller density differs depending on how many years have passed since treatments began. Stolon density was the second-most responsive component; the predictor variables were found to have no statistically significant interaction, meaning their effects on stolon density are independent of one another. Ramet density, ramets per stolon, and axillary bud metabolic activity and density were found to be independent of annual precipitation amount for 2021. The results indicate that multiple-year extreme wet and multiple-year extreme dry conditions in the Southwest will both likely reduce tiller and stolon densities in black grama patches. Prolonged drought conditions reduced tiller and stolon production in black grama because of negative legacies from previous years. Reduced production during prolonged wet conditions could be due to increased competition between adjacent plants.
ContributorsSutter, Bryce Madison (Author) / Sala, Osvaldo E (Thesis advisor) / Makings, Elizabeth (Committee member) / Wojciechowski, Martin F (Committee member) / Arizona State University (Publisher)
Created2022