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.
Displaying 1 - 10 of 358
Filtering by
- All Subjects: Social Research
- All Subjects: Molecular Biology
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
Communication skills within dating contexts are developed during the adolescent years, and are associated with a lifelong ability to have satisfying, enduring, and non-violent partnerships. As such, they are currently and increasingly implemented into both more general forms of healthy relationship education, as well as that targeting the prevention of teen dating violence specifically. Reaching Mexican American youth with culturally and developmentally appropriate relationship education, including communication skills, may be particularly important given their earlier transitions to marital and parenting relationships, acculturative stressors that present them with unique coupling challenges, and their higher rates of teen dating violence as compared to European American youth. We know very little about how Mexican American dating couples communicate about areas of conflict. This dissertation research utilizes Bell and Naugle's (2008) framework of interpersonal violence to explore how cultural and developmental considerations may be integrated in order to better understand how communication behaviors contribute to Mexican American middle adolescents' experiences with dating conflict. I use an observational study design in order to 1.) Qualitatively explore the communication strategies used by a sample of committed couples, including integration of culturally- and developmentally-relevant contexts, 2.) Quantitatively examine whether couple-level discrepancies in acculturation are associated with observed negativity, including whether this relationship may be mediated by dissimilar gender-related beliefs, and to 3.) Review empirical findings pertaining to the communication behaviors of Mexican American adolescents and to integrate ecodevelopmental theory in said framework as informed by Papers 1, 2, and literature specific to this topic area. The ultimate aim of this dissertation research is to generate findings that may improve the dating health of Mexican American adolescents living in the United States.
ContributorsAdams, Heidi (Author) / Rankin Williams, Lela (Thesis advisor) / Marsiglia, Flavio (Committee member) / Anthony, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation explores vulnerability to extreme heat hazards in the Maricopa County, Arizona metropolitan region. By engaging an interdisciplinary approach, I uncover the epidemiological, historical-geographical, and mitigation dimensions of human vulnerability to extreme heat in a rapidly urbanizing region characterized by an intense urban heat island and summertime heat waves. I first frame the overall research within global climate change and hazards vulnerability research literature, and then present three case studies. I conclude with a synthesis of the findings and lessons learned from my interdisciplinary approach using an urban political ecology framework. In the first case study I construct and map a predictive index of sensitivity to heat health risks for neighborhoods, compare predicted neighborhood sensitivity to heat-related hospitalization rates, and estimate relative risk of hospitalizations for neighborhoods. In the second case study, I unpack the history and geography of land use/land cover change, urban development and marginalization of minorities that created the metropolitan region's urban heat island and consequently, the present conditions of extreme heat exposure and vulnerability in the urban core. The third study uses computational microclimate modeling to evaluate the potential of a vegetation-based intervention for mitigating extreme heat in an urban core neighborhood. Several findings relevant to extreme heat vulnerability emerge from the case studies. First, two main socio-demographic groups are found to be at higher risk for heat illness: low-income minorities in sparsely-vegetated neighborhoods in the urban core, and the elderly and socially-isolated in the expansive suburban fringe of Maricopa County. The second case study reveals that current conditions of heat exposure in the region's urban heat island are the legacy of historical marginalization of minorities and large-scale land-use/land cover transformations of natural desert land covers into heat-retaining urban surfaces of the built environment. Third, summertime air temperature reductions in the range 0.9-1.9 °C and of up to 8.4 °C in surface temperatures in the urban core can be achieved through desert-adapted canopied vegetation, suggesting that, at the microscale, the urban heat island can be mitigated by creating vegetated park cool islands. A synthesis of the three case studies using the urban political ecology framework argues that climate changed-induced heat hazards in cities must be problematized within the socio-ecological transformations that produce and reproduce urban landscapes of risk. The interdisciplinary approach to heat hazards in this dissertation advances understanding of the social and ecological drivers of extreme heat by drawing on multiple theories and methods from sociology, urban and Marxist geography, microclimatology, spatial epidemiology, environmental history, political economy and urban political ecology.
ContributorsDeclet-Barreto, Juan (Author) / Harlan, Sharon L (Thesis advisor) / Bolin, Bob (Thesis advisor) / Hirt, Paul (Committee member) / Boone, Christopher (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 phenomenological qualitative study examines the experiences of volunteer tourism on host communities using social representations theory. The experiences of three stakeholder-groups (community residents, volunteers, and nongovernmental organizations) are considered. Overall objectives of this project are to investigate the following questions: a) what are the effects of volunteer tourism on a community as perceived by different stakeholders; b) what effects do volunteer tourists have on the community compared to other forms of tourism as perceived by different stakeholders; c) how do the various stakeholders perceive the different forms of tourism in communities in which they live or work; and d) why and how do nongovernmental organizations (NGOs) use volunteer tourism as a strategy for their projects. This study attempts to describe and interpret these meanings with a high degree of depth and richness using interviews, observation, and document analysis. Each chapter is written as a stand-alone paper to be published in a journal and describes the perspectives of the three groups interviewed with the final chapter a summary and comparison from all three groups. Findings show that there are both positive and negative impacts of volunteer tourism in favela communities, with the majority of the three groups expressing its positives and its importance to the community. All groups mentioned similar positive and negative elements of volunteer tourism with some elements that were unique to each group. This study also attempted to compare and contrast the differences between volunteer tourism and favela tours. The findings show that volunteer tourism helps recreate the social representations of the favela thereby improving self-esteem in the community, helps breakdown preconceptions, and helps create community pride. The community feels as equals with the volunteers and describes the interactions as friendships, sharing cultural experiences, and exchanging of knowledge. Conversely, all three groups described favela tours as dehumanizing using words like `safari tour' or `zoo tour' and felt that their community was being sold as a commodity. However, the interviews showed that all three groups, although had strong opinions about the ethical implications of favela tours, still felt conflicted when comparing it with some of the potential social and economic benefits that it may bring.
ContributorsAquino, Jessica Faustini (Author) / Andereck, Kathleen (Thesis advisor) / Mcgehee, Nancy (Committee member) / Phillips, Rhonda (Committee member) / Wang, Lili (Committee member) / Arizona State University (Publisher)
Created2013
Description
There is a popular notion that creativity is highly valued in our culture. However, those "in the trenches," people in creative endeavors that actually produce the acts of creativity, say this is not so. There is a negative correlation between the value stated and the true value placed on creativity by our contemporary culture. The primary purpose of this study was to investigate that correlation as well as a possible contributing factor to this negative correlation--the fear of risk involved in enacting and accepting creativity. The methods used in this study were literature review and interview. An extensive literature review was done, as much has been written on creativity. The review was done in four parts: 1) the difficulty in defining creativity; 2) fear and the fear of creativity; 3) solutions - ways to be, express, and accept creativity; and 4) the plethora of articles written about creativity. Six one-on-one interviews were conducted with creative individuals from a variety of commercial creative endeavors. Creatives in commercial fields were chosen specifically because of their ability to influence the culture. The results of this study showed that the hypothesis, that there is a negative correlation between the value stated and the true value placed on creativity, is true. The fear of risk involved in enacting and accepting creativity as a factor in this dichotomy was also shown to be true.
ContributorsGelman, Howard P (Author) / Heywood, Wil (Thesis advisor) / Patel, Mookesh (Committee member) / Knox, Gordon (Committee member) / Arizona State University (Publisher)
Created2013