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
Este trabajo examina la producción literaria y cultural chicana/méxicosudoesteña de las distintas épocas coloniales del sudoeste: la época colonial española (1521-1821), la época colonial angloamericana (1848-1965) y la época poscolonial (1965-presente) para ver hasta qué punto siguen vigentes los legados coloniales dentro de un contexto contemporáneo. Avanzamos la hipótesis que, de la larga residencia histórica y geográfica de las personas hispanomexicanas en el sudoeste, se han producidos textos simbólicos donde se registran dos o más discursos residuos cuyo origen es una ideología dominante. El capítulo 1 plantea y detalla la hipótesis, reseña los numerosos estudios existentes, describe el marco teórico y da la división en capítulos. En el capítulo 2, se da de manera detallada el método crítico: la definición del colonialismo clásico según la teoría de Mario Barrera, la relación colonizador/colonizado aportada por Albert Memmi y los conceptos del tercer espacio híbrido, el mestizaje y el imaginario decolonial asociados con la época poscolonial como ofrecidos respectivamente por Homi Bhabha, Rafael Pérez-Torres y Emma Pérez. El capítulo 3 ofrece un análisis de la época colonial española vía dos obras nuevomexicanas: el poema épico Historia de la Nueva México (1610) de Gaspar Pérez de Villagrá y el drama Los comanches (c.1779) de anónimo. El capítulo 4 trata la colonización angloamericana en las obras The Squatter and the Don (1885) de María Amparo Ruiz de Burton y Dew on the Thorn (escrita en los 1940; publicada en 1997) de Jovita González de Mireles. El capítulo 5 examina la época poscolonial vía la obra Los muertos también cuentan (1995) de Miguel Méndez. Una lectura de la literatura chicana/méxicosudoesteña revela la presencia de varios personajes típicos asociados cada uno a una diferente época histórica desde el conquistador español hasta un mexicano recién inmigrado, quienes no han podido evadir la correspondiente presencia de un grupo dominante u colonizador. Con base en una investigación de las cinco obras seleccionadas, se muestra cómo las relaciones coloniales se forman y se transforman y luego se manifiestan en un contexto contemporáneo, desplazando por ende nuestro entendimiento de las relaciones coloniales como un simple proyecto binario de dominación y subordinación.
ContributorsFonseca, Vanessa (Author) / Hernández-G., Manuel De Jesús (Thesis advisor) / Rosales, Jesus (Committee member) / García-Fernández, Carlos Javier (Committee member) / Volek, Emil (Committee member) / Horan, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2013
Description
Set in the former Yugoslavia, contemporary Bosnia and Herzegovina, and Midwest America, the collection of short stories follows the complicated trajectory of war-survivor to refugee and, then, immigrant. These stories---about religious prisoners who are not at all religious, about young, philosophizing boys tempting the bullets of snipers, about men retracing their fathers' steps over bridges that no longer exist---grapple with memory, imagination, and the nature of art, and explore the notion of writer as witness.
ContributorsHusić, Vedran (Author) / Pritchard, Melissa (Thesis advisor) / Ison, Tara (Committee member) / Turchi, Peter (Committee member) / Arizona State University (Publisher)
Created2013
Description
A simple passion for reading compels many to enter the university literature classroom. What happens once they arrive may fuel that passion, or possibly destroy it. A romanticized relationship with literature proves to be an obstacle that hinders a deeper and richer engagement with texts. Primary research consisting of personal interviews, observations, and surveys, form the source of data for this dissertation project which was designed to examine how literature teachers engage their students with texts, discussion, and assignments in the university setting. Traditionally text centered and resolute, literature courses will need refashioning if they are to advance beyond erstwhile conventions. The goal of this study is to create space for a dialogue about the need for a pedagogy of literature.
ContributorsSanchez, Shillana (Author) / Goggin, Maureen (Thesis advisor) / Tobin, Beth (Thesis advisor) / Rose, Shirley (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
En el siglo XXI nuestra vida se está cruzando constantemente con la tecnología, tanto que algunos declaran que nuestro mundo se ha hecho posthumano, ya que no se puede separar al ser humano de la máquina. Aunque algunos se sientan amenazados por estas tecnologías, otros están abrazando la Red Mundial, aprovechándose de las infinitas oportunidades que ofrece. Uno de estos elementos fundamentales que internet posibilita es la capacidad de comunicarse directamente con otras personas. El blog por ejemplo, o bitácora en español, permite que los usuarios se proyecten a sí mismos o a sus pseudo-identidades, sus pensamientos e ideas a través del texto que escriben en internet. También sus lectores pueden responder a estos autores inmediatamente. Los posts publicados--entradas en una página web--, aunque aparecen cronológicamente, son episodios fragmentados. Pero el blog no se limita a la producción de un texto sino que el autor puede también "jugar" con el cuerpo del texto para añadir hipervínculos y multimedia. Esta forma de escribir está cambiando lo que se considera "válido" como texto, incluso lo que se considera literatura. El objetivo de este trabajo no es estudiar la literatura digital en su totalidad, sino específicamente en algunas obras escritas por mujeres en internet. Si se considera la escritura digital como una forma de arte marginalizada, se podría decir que la escritura realizada por mujeres en internet experimenta una doble-marginalidad debido al hecho de que la literatura de mujeres siempre ha sido marginal al canon. Este estudio tomará un punto de vista transatlántico, incluyendo en el mismo a varias escritoras hispanohablantes de diferentes edades, experiencias y con variados motivos en su trabajo que publican sus obras en internet. Estas autoras incluyen las blogueras Almudena Montero (española) yMaría Amelia López Soliño (española); la periodista ciudadana Yoanis Sánchez (cubana); y la poeta digital/crítica Belén Gache (española-argentina). En esta tesis he explorado y considerado la noción de que el internet sirve como un medio de democratización puesto que, hasta cierto punto, las fronteras de género y nacionalidad desaparecen. Por esta razón, este trabajo va a considerar varias teorías tales como el postmodernismo, las teorías sobre la escritura de mujeres y teorías sobre la democratización de la tecnología para analizar la literatura que se encuentra en la red. Aunque las escritoras analizadas en este proyecto son distintas, y usan la tecnología de maneras diferentes, tienen una misma meta: expresarse libremente y comunicarse directamente con sus lectores al conectarse a internet. Mi hipótesis de trabajo consiste en que estas mujeres escriben de una manera particular--es decir, que no escriben igual a los hombres que escriben en internet--y que la red ofrece una plataforma única a las mujeres: en este espacio ellas son más activas--en oposición a la literatura tradicional-- en cuanto a compartir y publicar su propio trabajo e ideas.
ContributorsByron, Jennifer E. (Author) / Urioste-Azcorra, Carmen (Thesis advisor) / Tompkins, Cynthia (Committee member) / García-Fernández, Carlos Javier (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation considers the literary and cultural response of the labor-class poets to the emerging forces of Foucauldian biopolitics in early modern Britain to shed new light on the cultural impacts of biopower upon the rural community in early modern Britain. The analysis demonstrates how the labor class literary response is characterized by an exterior experience with the nonhuman in an alternative mode to the Wordsworthian experience of the interior. I then use labor-class poets to counter Wordsworthian notions of the immaterial State population through a critical expose of state-Subject, subject-object, and human nonhuman exterior relations as they are depicted in the labor-class poetry of late eighteenth and early nineteenth century Britain. Employing an object-ontological reading of community, I explore how the effects of biopower were inscribed in the literary artifacts of the labor-class. As a final consideration, I explore the response to postcolonial biopolitics in J.M. Coetzee's 1999 novel, Disgrace. The research takes a focused historical view, surveying a range of literary, political, and historical texts between 1760-1840 to offer new readings of Robert Bloomfield, Robert Burns, John Clare, William Cobbett, Ebenezer Elliott, Olivier Goldsmith, James Hogg, and William Wordsworth. In complement, the research offers a new reading of postcolonial biopolitics in the contemporary work of J.M Coetzee.
ContributorsBisnoff, Robert W (Author) / Lussier, Mark S. (Thesis advisor) / Bixby, Patrick (Committee member) / Broglio, Ron (Committee member) / Arizona State University (Publisher)
Created2013