Matching Items (984)
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
With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements, college students most frequently received information from friends and family. STEM majors in fields unrelated to health who were taking a supplement were found to be less likely to receive information about the supplement from a medical practitioner than those in health fields or those in non-STEM majors (-26.9%, p=0.018). STEM majors in health-related fields were 15.0% more likely to treat colds and/or cold symptoms with research-supported methods identified from reliable sources, while non-health STEM and non-STEM majors were more likely to take unsupported cold treatments (p=0.010). Surveyed students, regardless of major, also stated they would trust a medical practitioner for supplement advice above other sources (88.0%), and the majority expressed a belief that dietary supplements are approved/regulated by the government (59.8%).
ContributorsPerez, Jacob Tanner (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
ContributorsChandler, N. Kayla (Author) / Neisewander, Janet (Thesis director) / Sanabria, Federico (Committee member) / Olive, M. Foster (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
I propose that norms regulate behaviors that negatively impact an individual's survival and reproduction. But because monitoring and enforcing of norms can be costly, individuals should be selective about which norms they police and under what circumstances they should do so. Two studies tested this idea by experimentally activating fitness-relevant motives and having participants answer questions about the policing of norms. The first study examined a norm prescribing respect for status and another proscribing sexual coercion. Results from Study 1 failed to support the hypotheses; activating a status-seeking motive did not have the predicted effects on policing of the respect-status norm nor did activating a mating motive have the predicted effects on policing of the respect-status norm or anti-coercion norm. Study 2 examined two new norms, one prescribing that people stay home when sick and the other proscribing people from having sex with another person's partners. Study 2 also manipulated whether self or others were the target of the policing. Study 2 failed to provide support; a disease avoidance motive failed to have effects on policing of the stay home when sick norm. Individuals in a relationship under a mating motive wanted less policing of others for violation of the mate poaching norm than those in a baseline condition, opposite of the predicted effects.
ContributorsSmith, M. Kristopher (Author) / Neuberg, L. Steven (Thesis director) / Presson, Clark (Committee member) / Hruschka, J. Daniel (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
Literature in public administration emphasizes a growing dissatisfaction with government on the part of residents. Where there tends to be a lack in the literature is in terms of solutions to this problem. We would like to argue that the engagement process itself has the power to foster a profound attitudinal shift on the part of both residents and government. This paper explores the structural and cultural barriers to satisfactory public engagement both from literature and a combination of policy analysis, semi-structured interviews and participatory observation within the City of Tempe. We then provide recommendations to the City of Tempe on how to overcome these barriers and effect authentic public engagement practices. With these new suggested practices and mindsets, we provide a way that people can have the power to create their own community.
ContributorsRiffle, Morgan (Co-author) / Tchida, Celina (Co-author) / Ingram-Waters, Mary (Thesis director) / Grzanka, Patrick (Committee member) / King, Cheryl (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
This thesis examines the relationship between unofficial, official, and parallel Islam in Uzbekistan following the end of the Soviet Union. Key touchstone moments in Uzbekistan during the twentieth-century show the history between unofficial and official Islam and the resulting precedents set for Muslims gathering against the government. This historical analysis shows how President Karimov and the Uzbek government view and approach Islam in the country following independence.
ContributorsTieslink, Evan (Author) / Batalden, Stephen (Thesis director) / Kefeli, Agnes (Committee member) / Saikia, Yasmin (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Politics and Global Studies (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2013-05
Description
Through this creative project, I executed a Distracted Driving Awareness Campaign at Arizona State University to raise awareness about the dangers of distracted driving, specifically texting while driving. As an Undergraduate Student Government Senator, my priority is the safety and success of students, both in and out of the classroom. By partnering with State Farm and AT&T, we were able to raise awareness about the dangers of distracted driving and collected over 200 pledges from students to never text and drive.
ContributorsHibbs, Jordan Ashley (Author) / Miller, Clark (Thesis director) / Parmentier, Mary Jane (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Department of Psychology (Contributor) / Graduate College (Contributor)
Created2014-05
Description
Teen dating violence is a significant problem in the U.S., with approximately 1 out of 3 teens experiencing some form of dating violence. BLOOM is a not-for-profit organization created by Donna Bartos. BLOOM's educators enter high schools in Arizona and present their educational program on dating abuse prevention. BLOOM's primary goal is to educate teens on how to prevent teen dating violence and empower them with the skills leading to healthy relationships. After participants complete their educational program, a feedback card is filled out with an open-response section. This project focused on the open response section to analyze feedback cards through a process of code development, coding, and tallying. Information provided by this project could assist BLOOM in re-evaluating their curriculum, appealing to future investors, and growing their program to reach more students. With a coding system in place, BLOOM will also be able to better assess the impact they have on the participants of their program.
ContributorsHarmon, Ashley Nicole (Author) / Bodman, Denise (Thesis director) / Dumka, Larry (Committee member) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / College of Liberal Arts and Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013