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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Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
Speciation is the fundamental process that has generated the vast diversity of life on earth. The hallmark of speciation is the evolution of barriers to gene flow. These barriers may reduce gene flow either by keeping incipient species from hybridizing at all (pre-zygotic), or by reducing the fitness of hybrids (post-zygotic). To understand the genetic architecture of these barriers and how they evolve, I studied a genus of wasps that exhibits barriers to gene flow that act both pre- and post-zygotically. Nasonia is a genus of four species of parasitoid wasps that can be hybridized in the laboratory. When two of these species, N. vitripennis and N. giraulti are mated, their offspring suffer, depending on the generation and cross examined, up to 80% mortality during larval development due to incompatible genic interactions between their nuclear and mitochondrial genomes. These species also exhibit pre-zygotic isolation, meaning they are more likely to mate with their own species when given the choice. I examined these two species and their hybrids to determine the genetic and physiological bases of both speciation mechanisms and to understand the evolutionary forces leading to them. I present results that indicate that the oxidative phosphorylation (OXPHOS) pathway, an essential pathway that is responsible for mitochondrial energy generation, is impaired in hybrids of these two species. These results indicate that this impairment is due to the unique evolutionary dynamics of the combined nuclear and mitochondrial origin of this pathway. I also present results showing that, as larvae, these hybrids experience retarded growth linked to the previously observed mortality and I explore possible physiological mechanisms for this. Finally, I show that the pre-mating isolation is due to a change in a single pheromone component in N. vitripennis males, that this change is under simple genetic control, and that it evolved neutrally before being co-opted as a species recognition signal. These results are an important addition to our overall understanding of the mechanisms of speciation and showcase Nasonia as an emerging model for the study of the genetics of speciation.
ContributorsGibson, Joshua D (Author) / Gadau, Jürgen (Thesis advisor) / Harrison, Jon (Committee member) / Pratt, Stephen (Committee member) / Verrelli, Brian (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
The principle of Darwinian evolution has been applied in the laboratory to nucleic acid molecules since 1990, and led to the emergence of in vitro evolution technique. The methodology of in vitro evolution surveys a large number of different molecules simultaneously for a pre-defined chemical property, and enrich for molecules with the particular property. DNA and RNA sequences with versatile functions have been identified by in vitro selection experiments, but many basic questions remain to be answered about how these molecules achieve their functions. This dissertation first focuses on addressing a fundamental question regarding the molecular recognition properties of in vitro selected DNA sequences, namely whether negatively charged DNA sequences can be evolved to bind alkaline proteins with high specificity. We showed that DNA binders could be made, through carefully designed stringent in vitro selection, to discriminate different alkaline proteins. The focus of this dissertation is then shifted to in vitro evolution of an artificial genetic polymer called threose nucleic acid (TNA). TNA has been considered a potential RNA progenitor during early evolution of life on Earth. However, further experimental evidence to support TNA as a primordial genetic material is lacking. In this dissertation we demonstrated the capacity of TNA to form stable tertiary structure with specific ligand binding property, which suggests a possible role of TNA as a pre-RNA genetic polymer. Additionally, we discussed the challenges in in vitro evolution for TNA enzymes and developed the necessary methodology for future TNA enzyme evolution.
ContributorsYu, Hanyang (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
Synechocystis sp PCC 6803 is a photosynthetic cyanobacterium that can be easily transformed to produce molecules of interest; this has increased Synechocystis’ popularity as a clean energy platform. Synechocystis has been shown to produce and excrete molecules such as fatty acids, isoprene, etc. after appropriate genetic modification. Challenges faced for large–scale growth of modified Synechocystis include abiotic stress, microbial contamination and high processing costs of product and cell material. Research reported in this dissertation contributes to solutions to these challenges. First, abiotic stress was addressed by overexpression of the heat shock protein ClpB1. In contrast to the wild type, the ClpB1 overexpression mutant (Slr1641+) tolerated rapid temperature changes, but no difference was found between the strains when temperature shifts were slower. Combination of ClpB1 overexpression with DnaK2 overexpression (Slr1641+/Sll0170+) further increased thermotolerance. Next, we used a Synechocystis strain that carries an introduced isoprene synthase gene (IspS+) and that therefore produces isoprene. We attempted to increase isoprene yields by overexpression of key enzymes in the methyl erythritol phosphate (MEP) pathway that leads to synthesis of the isoprene precursor. Isoprene production was not increased greatly by MEP pathway induction, likely because of limitations in the affinity of the isoprene synthase for the substrate. Finally, two extraction principles, two–phase liquid extraction (e.g., with an organic and aqueous phase) and solid–liquid extraction (e.g., with a resin) were tested. Two–phase liquid extraction is suitable for separating isoprene but not fatty acids from the culture medium. Fatty acid removal required acidification or surfactant addition, which affected biocompatibility. Therefore, improvements of both the organism and product–harvesting methods can contribute to enhancing the potential of cyanobacteria as solar–powered biocatalysts for the production of petroleum substitutes.
ContributorsGonzalez Esquer, Cesar Raul (Author) / Vermaas, Willem (Thesis advisor) / Chandler, Douglas (Committee member) / Bingham, Scott (Committee member) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation integrates humanities with social science methodologies within a critical framework, seeking to explore the relationship between the neoliberal restructuring and the intersection of gender, class and heteronormativity in contemporary China. In this project, neoliberalism is conceptualized as an art of governance centering on the intersection of race, gender, class and sexuality to create market subjects and sustain market competition. Focusing on China's recent socio-economic and cultural upheavals, this dissertation tries to address these questions: 1. How have class inequalities, binaristic gender and heteronormative discourses been employed intersectionally by the Chinese state to facilitate China's social transformation? 2. How has this process been justified and consolidated through the intersection of gender, class, sexuality and race? 3. How do the marginalized groups respond to these material and cultural practices? Building on the discursive analysis of China's televised 60th anniversary ceremony and If You Are the One, a popular Chinese reality show, as well as the data from the interview, focus group and participant observation of more than 100 informants, it is found that the intersection of gender, class and heteronormativity is central to China's neoliberal transition. A group of flexible and cheap laborers have been disarticulated and rearticulated from the population as the voluntary servitude to China's marketization and re-integration with the global economy. New controlling images, such as the bourgeois nucleus family, are created to legitimize this process. However, these disparate material and discursive practices have entailed contradictions and conflicts within the intersectional biopolitical system, and created contingent spaces of ungovernability for the marginalized groups. Building on these discursive analyses and empirical data, I reconceptualize intersectionality as a multi-dimensional-and-directional network to regulate and manage power for social organization and regulation, which grounds the biopolitical basics for the neoliberal economy. Thus I argue that we need to engage with the dynamics between the intersectional biopolitical structure and people's emerging experiences to construct a grounded utopia alternative to the neoliberal dominance for substantive social changes.
ContributorsZhang, Charlie Yi (Author) / Quan, H. L. T. (Thesis advisor) / Fonow, Mary Margaret (Thesis advisor) / Martinez, Jacqueline M. (Committee member) / Lee, Charles T. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Gender and sex are often conflated. Our laws, policies, and even science establish sex and gender as intrinsically linked and dimorphic in nature. This dissertation examines the relationship between sex and gender and the repercussions of this linked dimorphism in the realms of law, politics, and science. Chapter One identifies the legal climate for changing one's sexual identity post-surgical reassignment. It pays particular attention to the ability of postsurgical transsexuals to marry in their acquired sex. Chapter Two considers the process for identifying the sex of athletes for the purposes of participation in sex-segregated athletic events, specifically the role of testing and standards for categorization. Chapter Three explores the process of identifying and assigning the sex of intersex children. Chapter Four examines the process of prenatal sex selection and its ethical implications. Chapter Four also offers an anticipatory governance framework to address these implications.
ContributorsParsi, John (Author) / Crittenden, Jack (Thesis advisor) / Guston, David H. (Committee member) / Marchant, Gary (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of the current study was to use structural equation modeling-based quantitative genetic models to characterize latent genetic and environmental influences on proneness to three discrete negative emotions in middle childhood, according to mother-report, father-report and in-home observation. One primary aim was to test the extent to which covariance among the three emotions could be accounted for by a single, common genetically- and environmentally-influenced negative emotionality factor. A second aim was to examine the extent to which different reporters appeared to be tapping into the same genetically- and environmentally-influenced aspects of each emotion. According to mother- and father-report, moderate to high genetic influences were evident for all emotions, with mother- and father-report of fear and father-report of anger showing the highest heritability. Significant common environmental influences were also found for mother-report of anger and sadness in both univariate and multivariate models. For observed emotion, anger was moderately heritable with no evidence for common environmental variance, but sadness, object fear and social fear all showed modest to moderate common environmental influences and no significant genetic variance. In addition, cholesky decompositions examining genetic and environmental influences across reporter suggested that despite considerable overlap between mother-report and father-report, there was also reporter-specific variance on anger, sadness, and fear. Specifically, there were significant common environmental influences on mother-report of anger- and sadness that were not shared with father-report, and genetic influences on father-report of sadness and fear that were not shared with mother-report. In-home observations were not highly correlated enough with parent-report to support multivariate analysis for any emotion. Finally, according to both mother- and father-report, a single set of genetic and environmental influences was sufficient to account for covariance among all three negative emotions. However, fear was primarily explained by genetic influences not shared with other emotions, and anger also showed considerable emotion-specific genetic variance. In both cases, findings support the value of a more emotion-specific approach to temperament, and highlight the need to consider distinctions as well as commonalities across emotions, reporters and situations.
ContributorsClifford, Sierra (Author) / Lemery, Kathryn (Thesis advisor) / Shiota, Michelle (Committee member) / Eisenberg, Nancy (Committee member) / Arizona State University (Publisher)
Created2013
Description
In the latter half of the nineteenth century, colleges and universities transformed their thinking of the body as they institutionalized physical education, recreational activities, and especially physical exercise. In this study, I examine the historical discourse on physical exercise and training during this period. I employ the theoretical and methodological practices of Michel Foucault's archeological and genealogical work to write a "history of the present." I challenge the essential narrative of physical fitness on college and university campuses. I also discuss nineteenth century notions of ethics and masculinity as a way of understanding twenty-first century ethics and masculinity. Ultimately, I use the historical discourse to argue that institutionalization of recreation and fitness centers and activities have less to do with health and well-being and more to do with disciplining bodies and controlling individuals.
ContributorsWells, Timothy (Author) / Carlson, David L. (Thesis advisor) / Sandlin, Jennifer (Committee member) / Margolis, Eric (Committee member) / Arizona State University (Publisher)
Created2012
Description
Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.
ContributorsEckalbar, Walter L (Author) / Kusumi, Kenro (Thesis advisor) / Huentelman, Matthew (Committee member) / Rawls, Jeffery (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2012
Description
Arnold Schoenberg's 1908-09 song cycle, Das Buch der hängenden Gärten [The Book of the Hanging Gardens], opus 15, represents one of his most decisive early steps into the realm of musical modernism. In the midst of personal and artistic crises, Schoenberg set texts by Stefan George in a style he called "pantonality," and described his composition as radically new. Though stylistically progressive, however, Schoenberg's musical achievement had certain ideologically conservative roots: the composer numbered among turn-of-the-century Viennese artists and thinkers whose opposition to the conventional and the popular--in favor of artistic autonomy and creativity--concealed a reactionary misogyny. A critical reading of Hanging Gardens through the lens of gender reveals that Schoenberg, like many of his contemporaries, incorporated strong frauenfeindlich [anti-women] elements into his work, through his modernist account of artistic creativity, his choice of texts, and his musical settings. Although elements of Hanging Gardens' atonal music suggest that Schoenberg valued gendered-feminine principles in his compositional style, a closer analysis of the work's musical language shows an intact masculinist hegemony. Through his deployment of uncanny tonal reminiscences, underlying tonal gestures, and closed forms in Hanging Gardens, Schoenberg ensures that the feminine-associated "excesses" of atonality remain under masculine control. This study draws upon the critical musicology of Susan McClary while arguing that Schoenberg's music is socially contingent, affected by the gender biases of his social and literary milieux. It addresses likely influences on Schoenberg's worldview including the philosophy of Otto Weininger, Freudian psychoanalysis, and a complex web of personal relationships. Finally, this analysis highlights the relevance of Schoenberg's world and its constructions of gender to modern performance practice, and argues that performers must consider interrelated historical, textual, and musical factors when interpreting Hanging Gardens in new contexts.
ContributorsGinger, Kerry Anne (Author) / FitzPatrick, Carole (Thesis advisor) / Dreyfoos, Dale (Committee member) / Mook, Richard (Committee member) / Norton, Kay (Committee member) / Ryan, Russell (Committee member) / Arizona State University (Publisher)
Created2012