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
The purpose of this study was to examine the attitudes and opinions of Navajo students toward the Navajo language and culture programs within the schools they were attending. Although in the final year of the No Child Left Behind, a majority of the 265 schools on and near the Navajo reservation have not been making Adequate Yearly Progress, a concern for the parents, teachers, administrators, school board members, and the Navajo Nation. The study entailed conducting a survey at five schools; three of which were not meeting the requirements of the No Child Left Behind. The purpose of the survey instrument (27 questions) administered to the students at the five schools was to examine their attitudes and opinions as to participating in Navajo language and culture programs, to determine if the programs assisted them in their academic achievements, and to examine whether these programs actually made a difference for schools in their Adequate Yearly Progress requirement Approximately 87% of 99 Navajo students, 55 boys and 58 girls, ages 9 through 14, Grades 3 through 8, who lived off the reservation in Flagstaff, Arizona and Gallup, New Mexico, and took the survey knew and spoke Navajo, but less fluently and not to a great extent. However, the students endorsed learning Navajo and strongly agreed that the Navajo language and culture should be part of the curriculum. Historically there have been schools such as the Rock Point Community School, Rough Rock Demonstration School, Borrego Pass Community School, and Ramah Community School that have been successful in their implementation of bilingual programs. The question presently facing Navajo educators is what type of programs would be successful within the context of the No Child Left Behind federal legislation. Can there be replications of successful Navajo language and culture programs into schools that are not making Adequate Yearly Progress?
ContributorsTsosie, David J (Author) / Spencer, Dee A. (Thesis advisor) / Appleton, Nicholas A. (Committee member) / Koerperich, Robbie (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
In order to adapt to a new culture and new language, children of immigrant families are faced daily with the responsibility of being the intermediaries between the family and the host culture through their language proficiency (Weisskirch & Alva, 2002). This thesis looks into the experiences of English-Spanish bilingual children as they bridge the gap between the family and the non-Spanish speaking community through their interpreting/translating skills. With an emphasis on children of Mexican-origin, the goal is to further understand and illuminate how these children manage this communication in an adult society, their feelings and thoughts about their experiences, and the child's perceptions about the influence that this experience may or may not have on their future. A sample of seventeen children agreed to participate in a semi-structured face-to-face interview to share their experiences. The data from these interviews were analyzed using a thematic analysis approach (Braun & Clarke, 2006). A priori themes of circumstantial bilingual and adaptive parentification were the initial focus of the research while being open to emerging themes. The children's accounts of their experiences indicated primarily that the Mexican-origin values of familism and respeto (respect) were a significant influence on them when they interpreted/translated for their family. With these traditional cultural values and norms as the groundwork, the sub-themes of normalcy and stress emerged as supportive elements of the circumstantial bilingual experience. Furthermore, the theme of adaptive parentification and the sub-themes of choice, expectation/responsibility to assist, and equality to parents offered further insight on how adaptive parentification can result as the roles of these children change. There was an emergent theme, identity negotiation, which increases our understanding of what the circumstantial bilingual child encounters as the attempt is made to negotiate his identity as an individual who has to mediate language between two opposing cultures. Due to the language brokering responsibility that are bestowed upon these children, it is concluded that communicative support by the parents is a necessary component of the parent-child relationship in order to nurture and develop these children as they negotiate and create their identity to become the successful leaders of tomorrow.
ContributorsCayetano, Catalina (Author) / Mean, Lindsey (Thesis advisor) / Waldron, Vincent (Committee member) / Gaffney, Cynthia (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of this study is to investigate the literacy practices of three members of Alcoholics Anonymous (A.A.) and to explore how they use these practices to support and maintain their recovery in their lives. This study also aims to examine how each participant used specialist language, enacted certain identities and acquired the secondary Discourse in A.A. through literacy use. This dissertation study is the result of in-depth interviewing in which each participant was interviewed three times for 90-minutes. These interviews were then transcribed and analyzed using discourse analysis. Study results are presented in three chapters, each one designated to one of the participants. Within these chapters is a life history (chronology) of the participant leading up to the point in which they got sober. The chapters also include a thematic discourse analysis of the interview transcripts across themes of literacy practice and topics in A.A. A conclusion is then presented to investigate how literacy was used from a sociocultural perspective in the study. Due to the emotionally charged nature of this dissertation, it has been formatted to present the stories of the participants first, leaving the theoretical framework, literature review and research methods to be included as appendices to the main text.
ContributorsClausen, Jennifer Ann (Author) / Marsh, Josephine (Thesis advisor) / Hayes, Elisabeth (Committee member) / Serafini, Frank (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
This study investigates the effectiveness of the use of Concept-Based Instruction (CBI) to facilitate the acquisition of Spanish mood distinctions by second semester second language learners of Spanish. The study focuses on the development of Spanish mood choice and the types of explanations (Rule-of-Thumb vs. Concept-based) used by five students before and after being exposed to Concept-Based Instruction regarding the choice of Spanish mood following various modalities .The students in this study were presented with a pedagogical treatment on Spanish mood choice that included general theoretical concepts based on Gal'perin's (1969, 1992) didactic models and acts of verbalization, which form part of a Concept-Based pedagogical approach. In order to ascertain the effectiveness of the use of concept-based tools to promote the ability to use Spanish mood appropriately over time, a pre and post-test was administered to the group in which students were asked to respond to prompts containing modalities that elicit the indicative and subjunctive moods, indicate their level of confidence in their response, and verbalize in writing a reason for their choice. The development of these abilities in learners exposed to CBI was assessed by comparing pre and post-test scores examining both forms and explanations for the indicative and subjunctive modality prompts given. Results showed that students continued to rely on Rule-of-Thumb explanations of mood choice but they did expand their use of conceptually-based reasoning. Although the quantitative and qualitative analyses of the results indicate that most students did improve their ability to make appropriate mood choices (forms and explanations) after the CBI treatment, the increased use of conceptually-based explanations for their mood choices led to both correct and incorrect responses.
ContributorsBeus, Eric (Author) / Lafford, Barbara (Thesis advisor) / Beas, Omar (Committee member) / Cerron-Palomino, Alvaro (Committee member) / Arizona State University (Publisher)
Created2013
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