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
It is commonly known that the left hemisphere of the brain is more efficient in the processing of verbal information, compared to the right hemisphere. One proposal suggests that hemispheric asymmetries in verbal processing are due in part to the efficient use of top-down mechanisms by the left hemisphere. Most evidence for this comes from hemispheric semantic priming, though fewer studies have investigated verbal memory in the cerebral hemispheres. The goal of the current investigations is to examine how top-down mechanisms influence hemispheric asymmetries in verbal memory, and determine the specific nature of hypothesized top-down mechanisms. Five experiments were conducted to explore the influence of top-down mechanisms on hemispheric asymmetries in verbal memory. Experiments 1 and 2 used item-method directed forgetting to examine maintenance and inhibition mechanisms. In Experiment 1, participants were cued to remember or forget certain words, and cues were presented simultaneously or after the presentation of target words. In Experiment 2, participants were cued again to remember or forget words, but each word was repeated once or four times. Experiments 3 and 4 examined the influence of cognitive load on hemispheric asymmetries in true and false memory. In Experiment 3, cognitive load was imposed during memory encoding, while in Experiment 4, cognitive load was imposed during memory retrieval. Finally, Experiment 5 investigated the association between controlled processing in hemispheric semantic priming, and top-down mechanisms used for hemispheric verbal memory. Across all experiments, divided visual field presentation was used to probe verbal memory in the cerebral hemispheres. Results from all experiments revealed several important findings. First, top-down mechanisms used by the LH primarily used to facilitate verbal processing, but also operate in a domain general manner in the face of increasing processing demands. Second, evidence indicates that the RH uses top-down mechanisms minimally, and processes verbal information in a more bottom-up manner. These data help clarify the nature of top-down mechanisms used in hemispheric memory and language processing, and build upon current theories that attempt to explain hemispheric asymmetries in language processing.
ContributorsTat, Michael J (Author) / Azuma, Tamiko (Thesis advisor) / Goldinger, Stephen D (Committee member) / Liss, Julie M (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
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
Perceptual learning by means of coherent motion training paradigms has been shown to produce plasticity in lower and higher-level visual systems within the human occipital lobe both supra- and subliminally. However, efficiency of training methods that produce consolidation in the visual system via coherent motion has yet to be experimentally determined. Furthermore, the effects of coherent motion training on reading comprehension, in clinical and normal populations, are still nascent. In the present study, 20 participants were randomly assigned to one of four experimental conditions. Two conditions had a participation requirement of four days while two conditions required eight days of participation. These conditions were further divided into 500 or 1000 trials per day (4 x 500, 4 x 1000, 8 x 500, 8 x 1000). Additional pre-test and post-test days were used to attain timed pre- and post-tests on the Wide Range Achievement Test IV (WRAT IV) reading comprehension battery. Furthermore, a critical flicker fusion threshold (CFFT) score was taken on a macular pigment densitometer on the pre-test and post-test day. Participants showed significant improvement in CFFT levels, WRAT IV reading comprehension, and speed of completion between pre-test and post-test; however, degree of improvement did not vary as a function of training condition. An interaction between training condition and degree of improvement was evident in coherent dot motion contrast scores, with significant training plasticity occurring in the 4 x 1000 and 8 x 500 conditions.
ContributorsGroth, Anthony (Author) / Náñez, José E. (Thesis advisor) / Hall, Deborah (Committee member) / Risko, Evan F. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specific dendritic morphologies are a hallmark of neuronal identity, circuit assembly, and behaviorally relevant function. Despite the importance of dendrites in brain health and disease, the functional consequences of dendritic shape remain largely unknown. This dissertation addresses two fundamental and interrelated aspects of dendrite neurobiology. First, by utilizing the genetic power of Drosophila melanogaster, these studies assess the developmental mechanisms underlying single neuron morphology, and subsequently investigate the functional and behavioral consequences resulting from developmental irregularity. Significant insights into the molecular mechanisms that contribute to dendrite development come from studies of Down syndrome cell adhesion molecule (Dscam). While these findings have been garnered primarily from sensory neurons whose arbors innervate a two-dimensional plane, it is likely that the principles apply in three-dimensional central neurons that provide the structural substrate for synaptic input and neural circuit formation. As such, this dissertation supports the hypothesis that neuron type impacts the realization of Dscam function. In fact, in Drosophila motoneurons, Dscam serves a previously unknown cell-autonomous function in dendrite growth. Dscam manipulations produced a range of dendritic phenotypes with alteration in branch number and length. Subsequent experiments exploited the dendritic alterations produced by Dscam manipulations in order to correlate dendritic structure with the suggested function of these neurons. These data indicate that basic motoneuron function and behavior are maintained even in the absence of all adult dendrites within the same neuron. By contrast, dendrites are required for adjusting motoneuron responses to specific challenging behavioral requirements. Here, I establish a direct link between dendritic structure and neuronal function at the level of the single cell, thus defining the structural substrates necessary for conferring various aspects of functional motor output. Taken together, information gathered from these studies can inform the quest in deciphering how complex cell morphologies and networks form and are precisely linked to their function.
ContributorsHutchinson, Katie Marie (Author) / Duch, Carsten (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newfeld, Stuart (Committee member) / Smith, Brian (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The academic literature on science communication widely acknowledges a problem: science communication between experts and lay audiences is important, but it is not done well. General audience popular science books, however, carry a reputation for clear science communication and are understudied in the academic literature. For this doctoral dissertation, I utilize Sam Harris's The Moral Landscape, a general audience science book on the particularly thorny topic of neuroscientific approaches to morality, as a case-study to explore the possibility of using general audience science books as models for science communication more broadly. I conduct a literary analysis of the text that delimits the scope of its project, its intended audience, and the domains of science to be communicated. I also identify seven literary aspects of the text: three positive aspects that facilitate clarity and four negative aspects that interfere with lay public engagement. I conclude that The Moral Landscape relies on an assumed knowledge base and intuitions of its audience that cannot reasonably be expected of lay audiences; therefore, it cannot properly be construed as popular science communication. It nevertheless contains normative lessons for the broader science project, both in literary aspects to be salvaged and literary aspects and concepts to consciously be avoided and combated. I note that The Moral Landscape's failings can also be taken as an indication that typical descriptions of science communication offer under-detailed taxonomies of both audiences for science communication and the varieties of science communication aimed at those audiences. Future directions of study include rethinking appropriate target audiences for science literacy projects and developing a more discriminating taxonomy of both science communication and lay publics.
ContributorsJohnson, Nathan W (Author) / Robert, Jason S (Thesis advisor) / Creath, Richard (Committee member) / Martinez, Jacqueline (Committee member) / Sylvester, Edward (Committee member) / Lynch, John (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