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
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
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
Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively unfolded protein, amyloid-beta can misfold and aggregate generating a variety of different species including numerous different soluble oligomeric species some of which are precursors to the neurofibrillary plaques. Various of the soluble amyloid-beta oligomeric species have been shown to be toxic to cells and their presence may correlate with progression of AD. Current treatment options target the dementia symptoms, but there is no effective cure or alternative to delay the progression of the disease once it occurs. Amyloid-beta aggregates show up many years before symptoms develop, so detection of various amyloid-beta aggregate species has great promise as an early biomarker for AD. Therefore reagents that can selectively identify key early oligomeric amyloid-beta species have value both as potential diagnostics for early detection of AD and as well as therapeutics that selectively target only the toxic amyloid-beta aggregate species. Earlier work in the lab includes development of several different single chain antibody fragments (scFvs) against different oligomeric amyloid-beta species. This includes isolation of C6 scFv against human AD brain derived oligomeric amyloid-beta (Kasturirangan et al., 2013). This thesis furthers research in this direction by improving the yields and investigating the specificity of modified C6 scFv as a diagnostic for AD. It is motivated by experiments reporting low yields of the C6 scFv. We also used the C6T scFv to characterize the variation in concentration of this particular oligomeric amyloid-beta species with age in a triple transgenic AD mouse model. We also show that C6T can be used to differentiate between post-mortem human AD, Parkinson's disease (PD) and healthy human brain samples. These results indicate that C6T has potential value as a diagnostic tool for early detection of AD.
ContributorsVenkataraman, Lalitha (Author) / Sierks, Michael (Thesis advisor) / Rege, Kaushal (Committee member) / Pauken, Christine (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
In the last years of the twentieth century, while the narrative of women in other Latin American countries has received critical attention, Bolivian women's narrative has been widely ignored. The fact that the voice of Bolivian women in Latin American feminist discourse is rarely discussed in Latin American criticism is enough to justify the present study. This work focuses on three prominent Bolivian writers: Gaby Vallejos, Giovanna Rivero Santa Cruz, and Erika Bruzonic. The short stories of these three authors are characterized by accentuating certain telluric features revealed in the background of their feminine/feminist narratives. At the same time, based on the American and European feminist literary critique, this work analyzes the feminine/feminist themes mounted in the narrative of these authors. Gaby Vallejos, with a cinematic style, chronicles the life and customs of the "valluno" context, building a mosaic of different voices in dialogue. Her topics revolve around binaries: life-death, and pain and pleasure, voicing condemnation for a patriarchal society. Ericka Bruzonic deals with women and identity, memory and the breaking of lineage as an imposing structure. Her themes are built around the cosmopolitism of "paceña" urban life, and her voice transgresses the binomials established by a patriarchal society. Finally Giovanna Rivero Santa Cruz takes the life and customs of the Santa Cruz and the Guarani culture and her plots weave these elements reaching for myths and taboos, involving the reader into her stories. In this manner, her narrative makes an incursion into the conscious and unconscious realm of the readers questioning their wealth of moral and social values, their notions of heterosexuality, and sexual taboos. The three writers, with different narrative styles yet dialogical, narrate various experiences of women from different regions, social classes, ages, education, and sexual orientations. Our authors give high value to the word and the body embedded in the culture, thereby affirming their woman's voice as Bolivians and their literary presence in the context of Latin American literature.
ContributorsLopez, Norma (Author) / Urioste-Ascorra, Carmen (Thesis advisor) / Tompkins, Cynthia (Committee member) / Rosales, Jesus (Committee member) / Arizona State University (Publisher)
Created2013
Community-based development: scaling up the correct use of misoprostol at home births in Afghanistan
Description
Globally, more than 350 000 women die annually from complications during pregnancy and childbirth (UNFPA, 2011). Nearly 99% of these, according to World Health Organization (WHO) trends (2010) occur in the developing world outside of a hospital setting with limited resources including emergency care (WHO, 2012; UNFPA, 2011). The most prevalent cause of death is postpartum hemorrhage (PPH), accounting for 25% of deaths according to WHO statistics (2012). Conditions in Afghanistan are reflective of the scope and magnitude of the problem. In Afghanistan, maternal mortality is thought to be among the highest in the world. The Afghan Mortality Survey (AMS) data implies that one Afghan woman dies about every 2 hours from pregnancy-related causes (AMS, 2010). Lack of empowerment, education and access to health care resources increase a woman's risk of dying during pregnancy (AMS, 2010). This project aims to investigate the prospects of scaling-up the correct use of misoprostol, a prostaglandin E1 analogue, to treat PPH in developing countries where skilled assistance and resources are scant. As there has been little published on the lessons learned from programs already in place, this study is experience-driven, based on the knowledge of industry experts. This study employs a concurrent triangulation approach to synthesize quantitative data obtained from previous studies with qualitative information gathered through the testimonies of key personnel who participated in pilot programs involving misoprostol. There are many obstacles to scaling-up training initiatives in Afghanistan and other low-resource areas. The analysis concludes that the most crucial factors for scaling-up community-based programs include: more studies analyzing lessons learns from community driven approaches; stronger partnerships with community health care workers; overcoming barriers like association with abortion, misuse and product issues; and a heightened global and community awareness of the severity of PPH without treatment. These results have implications for those who actively work in Afghanistan to promote maternal health and other countries that may use Afghanistan's work as a blueprint for reducing maternal mortality through community-based approaches. Keywords: Afghanistan, community-based interventions, community-driven, maternal mortality, MDG5, misoprostol, postpartum hemorrhage, reproduction, scale-up
ContributorsCristy, Candice (Author) / Grossman, Gary (Thesis advisor) / Parmentier, Mary-Jane (Committee member) / Byrd, Denise (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
The purpose of my dissertation project is to understand how Same-Gender Loving (SGL) Black Christian men negotiate their sexuality and spirituality in spaces that are not always accepting of SGL people, by examining on how Black SGL men perform their sexual identities within hegemonic institutions that often deny their existence or outwardly seek to exclude them from their communities. I have identified three scripts that Black SGL men often follow within Black religious settings. The first script that SGL people often follow in the church is that of deliverance-- confessing their same-gender desires and maintaining that they have been delivered from those desires The second is "don't ask don't tell" performed by men who many believe and suspect of being SGL; so long as they do not publicly affirm these beliefs they are able to hold a variety of positions in their religious communities.. The last script involves accepting one's same-gender desires and also affirming one's Christian beliefs, proclaiming that the two are not at odds with one another. I examine how these scripts and/or others are performed by and on the bodies of Black SGL males in two distinct sites. The first is the career and music of former gospel star Anthony Charles Williams II (Tonex / B. Slade), who has utilized the three scripts at various times in his career. The next site is that of theatre, where I explore how these scripts have been employed in dramatic texts. By reading Christian Black SGL performance through its theological parameters, I aim to discern the avenues in which Black people in the United States are able to perform same-gender sexual identities in spaces that are constructed as "homophobic," and in so doing combat the narrative of hyper-homophobia in Black communities.
ContributorsChester, Tabitha Jamie Mary (Author) / Anderson, Lisa (Thesis advisor) / Leong, Karen J (Committee member) / Honegger, Gitta (Committee member) / Arizona State University (Publisher)
Created2013
Description
This study was done in collaboration with the Kino Border Initiative. The Kino Border Initiative is a Catholic, bi-national organization run by Missionary Sisters of the Eucharist, Jesuit priests and lay people. The organization is dedicated to providing services to recently deported migrants and migrants-in-transit through their soup kitchen, women's shelter and first aid station in Nogales, Sonora. Based on their experiences in the women's shelter, the Missionary Sisters of the Eucharist and researcher sought out to further understand migrant women's experiences of gender-based violence prior to migration. Using data collected by the Sisters, it was decided to use an analysis rooted in testimonio, and, in this way, use the women's words as a foundational basis for understanding the migration of women. The analysis is based on 62 testimonies related to women's histories of violence and their migration experiences, and the information from 74 intake questionnaires that were all analyzed retroactively. The analysis of data and testimonios has led to the realization that violence suffered by migrant women is not limited to the journey itself, and that 71% of women report having suffered some sort of violence either prior to or during migration. Often times, the first experiences of violence originated in their homes when they were children and continue to repeat itself throughout their lifetimes in varied forms. Their stories reveal how the decision to migrate is a consequence to the transnational and structural violence that pushes women to seek out ways to survive and provide for their families.
ContributorsConrad, Marla (Author) / Elenes, C. Alejandra (Thesis advisor) / Simmons, William P. (Committee member) / Téllez, Michelle (Committee member) / Arizona State University (Publisher)
Created2013