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
This dissertation investigates the long-term consequences of human land-use practices in general, and in early agricultural villages in specific. This pioneering case study investigates the "collapse" of the Early (Pre-Pottery) Neolithic lifeway, which was a major transformational event marked by significant changes in settlement patterns, material culture, and social markers. To move beyond traditional narratives of cultural collapse, I employ a Complex Adaptive Systems approach to this research, and combine agent-based computer simulations of Neolithic land-use with dynamic and spatially-explicit GIS-based environmental models to conduct experiments into long-term trajectories of different potential Neolithic socio-environmental systems. My analysis outlines how the Early Neolithic "collapse" was likely instigated by a non-linear sequence of events, and that it would have been impossible for Neolithic peoples to recognize the long-term outcome of their actions. The experiment-based simulation approach shows that, starting from the same initial conditions, complex combinations of feedback amplification, stochasticity, responses to internal and external stimuli, and the accumulation of incremental changes to the socio-natural landscape, can lead to widely divergent outcomes over time. Thus, rather than being an inevitable consequence of specific Neolithic land-use choices, the "catastrophic" transformation at the end of the Early Neolithic was an emergent property of the Early Neolithic socio-natural system itself, and thus likely not an easily predictable event. In this way, my work uses the technique of simulation modeling to connect CAS theory with the archaeological and geoarchaeological record to help better understand the causes and consequences of socio-ecological transformation at a regional scale. The research is broadly applicable to other archaeological cases of resilience and collapse, and is truly interdisciplinary in that it draws on fields such as geomorphology, computer science, and agronomy in addition to archaeology.
ContributorsUllah, Isaac (Author) / Barton, C. Michael (Thesis advisor) / Banning, Edward B. (Committee member) / Clark, Geoffrey (Committee member) / Arrowsmith, J. Ramon (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 causes and consequences of stylistic change have been a concern of archaeologists over the past several decades. The actual process of stylistic innovation, however, has received less attention. This project explores the relationship between the process of stylistic innovation on decorated pottery and the social context in which it occurred in the Hohokam area of south-central Arizona between A.D. 800 and 1300. This interval was punctuated by three episodes of reorganization, each of which was characterized to varying degrees by significant shifts in ideology, economics, and politics. Each reorganization episode was also accompanied by a rapid profusion of stylistic innovation on buff ware pottery. The goal of this study was to build a framework to understand the variation in the process of innovation as a response to different incentives and opportunities perceived in the changing social environment. By bringing stylistic analyses and provenance data together for the first time in Hohokam red-on-buff studies, I investigated how the process of innovation was variously influenced by social reorganizations at three different periods of time: the 9th, 11th, and 12th centuries A.D. Four variables were used to evaluate the process of innovation at each temporal period: 1) The origin of a stylistic invention, 2) the rate of its adoption, 3) the pattern of its adoption, and 4) the uniformity of its adoption among all buff ware potting communities. To accomplish the task, stylistic innovations and provenance were recorded on over 3,700 red-on-buff sherds were analyzed from 20 sites in the Phoenix Basin. The innovation process was found to vary with each reorganization episode, but often in different ways than expected. The results revealed the complexity and unpredictability of the process of stylistic innovation among the Hohokam. They also challenged some assumptions archaeologists have made regarding the scale and extent of the changes associated with some of the reorganization episodes. The variables utilized to measure the innovation process were found to be effective at providing a composite picture of that process, and thus warrant broader application to other archaeological contexts.
ContributorsLack, Andrew D (Author) / Abbott, David R. (Thesis advisor) / Hegmon, Michelle (Committee member) / Spielmann, Katherine A. (Committee member) / Nelson, Ben A. (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
Irrigation agriculture has been heralded as the solution to feeding the world's growing population. To this end, irrigation agriculture is both extensifying and intensifying in arid regions across the world in an effort to create highly productive agricultural systems. Over one third of modern irrigated fields, however, show signs of serious soil degradation, including salinization and waterlogging, which threaten the productivity of these fields and the world's food supply. Surprisingly, little ecological data on agricultural soils have been collected to understand and address these problems. How, then, can expanding and intensifying modern irrigation systems remain agriculturally productive for the long-term? Archaeological case studies can provide critical insight into how irrigated agricultural systems may be sustainable for hundreds, if not thousands, of years. Irrigation systems in Mesopotamia, for example, have been cited consistently as a cautionary tale of the relationship between mismanaged irrigation systems and the collapse of civilizations, but little data expressly link how and why irrigation failed in the past. This dissertation presents much needed ecological data from two different regions of the world - the Phoenix Basin in southern Arizona and the Pampa de Chaparrí on the north coast of Peru - to explore how agricultural soils were affected by long-term irrigation in a variety of social and economic contexts, including the longevity and intensification of irrigation agriculture. Data from soils in prehispanic and historic agricultural fields indicate that despite long-lived and intensive irrigation farming, farmers in both regions created strategies to sustain large populations with irrigation agriculture for hundreds of years. In the Phoenix Basin, Hohokam and O'odham farmers relied on sedimentation from irrigation water to add necessary fine sediments and nutrients to otherwise poor desert soils. Similarly, on the Pampa, farmers relied on sedimentation in localized contexts, but also constructed fields with ridges and furrows to draw detrimental salts away from planting surfaces in the furrows on onto the ridges. These case studies are then compared to failing modern and ancient irrigated systems across the world to understand how the centralization of management may affect the long-term sustainability of irrigation agriculture.
ContributorsStrawhacker, Colleen (Author) / Spielmann, Katherine A. (Thesis advisor) / Hall, Sharon J (Committee member) / Nelson, Margaret C. (Committee member) / Sandor, Jonathan A (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation research investigates both spatial and temporal aspects of Bronze Age land use and land cover in the Eastern Mediterranean using botanical macrofossils of charcoal and charred seeds as sources of proxy data. Comparisons through time and over space using seed and charcoal densities, seed to charcoal ratios, and seed and charcoal identifications provide a comprehensive view of island vs. mainland vegetative trajectories through the critical 1000 year time period from 2500 BC to 1500 BC of both climatic fluctuation and significant anthropogenic forces. This research focuses particularly on the Mediterranean island of Cyprus during this crucial interface of climatic and human impacts on the landscape. Macrobotanical data often are interpreted locally in reference to a specific site, whereas this research draws spatial comparisons between contemporaneous archaeological sites as well as temporal comparisons between non-contemporaneous sites. This larger perspective is particularly crucial on Cyprus, where field scientists commonly assume that botanical macrofossils are poorly preserved, thus unnecessarily limiting their use as an interpretive proxy. These data reveal very minor anthropogenic landscape changes on the island of Cyprus compared to those associated with contemporaneous mainland sites. These data also reveal that climatic forces influenced land use decisions on the mainland sites, and provides crucial evidence pertaining to the rise of early anthropogenic landscapes and urbanized civilization.
ContributorsKlinge, JoAnna M (Author) / Fall, Patricia L. (Thesis advisor) / Falconer, Steven E. (Committee member) / Brazel, Anthony J. (Committee member) / Pigg, Kathleen B (Committee member) / Arizona State University (Publisher)
Created2013
Description
This project examines the social and economic factors that contributed to the development of a specialist-based economy among the Phoenix Basin Hohokam. In the Hohokam case, widespread dependence on the products of a few concentrated pottery producers developed in the absence of political centralization or hierarchical social arrangements. The factors that promoted intensified pottery production, therefore, are the keys to addressing how economic systems can expand in small-scale and middle-range societies. This dissertation constructs a multi-factor model that explores changes to the organization of decorated pottery production during a substantial portion of the pre-Classic period (AD 700 - AD 1020). The analysis is designed to examine simultaneously several variables that may have encouraged demand for ceramic vessels made by specialists. This study evaluates the role of four factors in the development of supply and demand for specialist produced red-on-buff pottery in Hohokam settlements. The factors include 1) agricultural intensification in the form of irrigation agriculture, 2) increases in population density, 3) ritual or social obligations that require the production of particular craft items, and 4) reduced transport costs. Supply and demand for specialist-produced pottery is estimated through a sourcing analysis of non-local pottery at 13 Phoenix Basin settlements. Through a series of statistical analyses, the study measures changes in the influence of each factor on demand for specialist-produced pottery through four temporal phases of the Hohokam pre-Classic period. The analysis results indicate that specialized red-on-buff production was initially spurred by demand for light-colored, shiny, decorated pottery, but then by comparative advantages to specialized production in particular areas of the Phoenix Basin. Specialists concentrated on the Snaketown canal system were able to generate light-colored, mica-dense wares that Phoenix Basin consumers desired while lowering transport costs in the distribution of red-on-buff pottery. The circulation of decorated wares was accompanied by the production of plainware pottery in other areas of the Phoenix Basin. Economic growth in the region was based on complementary and coordinated economic activities between the Salt and the Gila River valleys.
ContributorsKelly, Sophia E (Author) / Abbott, David R. (Thesis advisor) / Darling, J. Andrew (Committee member) / Moore, Gordon (Committee member) / Spielmann, Katherine A. (Committee member) / Arizona State University (Publisher)
Created2013