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
This study examined the role of substance use in the relationship between the working alliance and outcome symptomatology. In this study, two groups of participants were formed: the at risk for substance abuse (ARSA) group consisted of participants who indicated 'almost always,' 'frequently,' 'sometimes,' or 'rarely' on either of two items on the Outcome Questionnaire-45.2 (OQ-45.2) (i.e., the eye-opener item: "After heavy drinking, I need a drink the next morning to get going" and the annoyed item: "I feel annoyed by people who criticize my drinking (or drug use)"). The non-ARSA group consisted of participants who indicated 'never' on both of the eye-opener and annoyed screening items on the OQ-45.2. Data available from a counselor-training center for a client participant sample (n = 68) was used. As part of the usual counselor training center procedures, clients completed questionnaires after their weekly counseling session. The measures included the Working Alliance Inventory and the OQ-45.2. Results revealed no significant differences between the ARSA and non-ARSA groups in working alliance, total outcome symptomology, or in any of the three subscales of symptomatology. Working alliance was not found to be significant in predicting outcome symptomatology in this sample and no moderation effect of substance use on the relationship between working alliance and outcome symptomatology was found. This study was a start into the exploration of the role of substance use in the relationship between working alliance and outcome symptomatology in individual psychotherapy. Further research should be conducted to better understand substance use populations in individual psychotherapy.
ContributorsHachiya, Laura Y (Author) / Bernstein, Bianca (Thesis advisor) / Tran, Giac-Thao (Committee member) / Homer, Judith (Committee member) / Arizona State University (Publisher)
Created2013
Description
Previous research indicates that difficulties in emotion regulation and greater dissociation from one's emotions are often observed among trauma survivors. Further, trauma survivors often show greater negative emotions such as anger, and diminished positive emotions such as happiness. Relatively less is known about the relationship between posttraumatic stress symptoms, dissociation, emotion regulation difficulties, and non-trauma related emotional experiences in daily life. This study examined whether greater reports of posttraumatic stress symptoms, difficulties in emotion regulation, and dissociative tendencies were associated with greater intensity of anger and lower intensity of happiness during a relived emotions task (i.e., recalling and describing autobiographical memories evoking specific emotions). Participants were 50 individuals who had experienced a traumatic event and reported a range of posttraumatic stress symptoms. Participants rated how they felt while recalling specific emotional memories, as well as how they remembered feeling at the time of the event. Results showed that dissociative tendencies was the best predictor of greater intensity of anger and, contrary to the hypothesis, dissociative tendencies was predictive of greater happiness intensity as well. These findings are consistent with previous research indicating a paradoxical effect of heightened anger reactivity among individuals with dissociative tendencies. In addition, researchers have argued that individuals with a history of traumatization do not report lower positive emotional experiences. The present findings may suggest the use of dissociation as a mechanism to avoid certain trauma related emotions (e.g, fear and anxiety), in turn creating heightened experiences of other emotions such as anger and happiness.
ContributorsTorres, Dhannia L (Author) / Robinson Kurpius, Sharon (Thesis advisor) / Roberts, Nicole A. (Committee member) / Homer, Judith (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
ABSTRACT Perfectionism has been conceptualized as a relatively stable, independent, multidimensional personality construct in research during the last two decades. Despite general agreement that perfectionism is dimensional in nature, analyses using these instruments vacillate between a dimensional approach and a categorical approach (Broman-Fulks, Hill, & Green, 2008; Stoeber & Otto, 2006). The goal of the current study was two-fold. One aim was to examine the structural nature of two commonly used measures of perfectionism, the APS-R and the HFMPS. Latent class and factor analyses were conducted to determine the dimensions and categories that underlie the items of these two instruments. A second aim was to determine whether perfectionism classes or perfectionism factors better predicted 4 criterion variables of career indecision. Results lent evidence to the claim that both the APS-R and HFMPS are best used as dimensional, rather than categorical instruments. From a substantive perspective, results indicated that both positive and negative aspects of perfectionism successfully predicted career indecision factors. The study concludes with a discussion of limitations, and implications for future research and counseling individuals with career indecision concerns.
ContributorsRohlfing, Jessica Elizabeth (Author) / Tracey, Terence J. G. (Thesis advisor) / Green, Samuel (Committee member) / Kinnier, Richard T. (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 study explored several training variables that may contribute to counseling trainees' multicultural counseling self-efficacy and multicultural case conceptualization ability. Specifically, this study aimed to examine the cognitive processes that contribute to multicultural counseling competence (MCC) outcome variables. Clinical experience, multicultural knowledge, and multicultural awareness are assumed to provide the foundation for the development of these outcome variables. The role of how a counselor trainee utilizes this knowledge and awareness in working with diverse populations has not been explored. Diversity cognitive complexity (DCC) quantifies the process by which a counselor thinks about different elements of diversity in a multidimensional manner. The current study examined the role of DCC on the relationship between training variables of direct clinical experience with diverse populations, multicultural knowledge, and multicultural awareness and the two training outcomes (multicultural counseling self-efficacy and multicultural case conceptualization ability). A total of one hundred and sixty-one graduate trainees participated in the study. A series of hypotheses were tested to examine the impact of DCC on the relationship between MCC predictors (multicultural knowledge, multicultural awareness, and direct contact hours with diverse clinical populations) and two MCC outcomes: multicultural counseling self-efficacy and multicultural case conceptualization ability. Hierarchical regression analyses were utilized to test whether DCC mediated or moderated the relationship between the predictors and the outcome variables. Multicultural knowledge and clinical hours with diverse populations were significant predictors of multicultural counseling self-efficacy. Multicultural awareness was a significant predictor of multicultural case conceptualization ability. Diversity cognitive complexity was not a significantly related to any predictor or outcome variable, thus all hypotheses tested were rejected. The results of the current study support graduate programs emphasizing counselor trainees gaining multicultural knowledge and awareness as well as direct clinical experience with diverse clinical populations in an effort to foster MCC. Although diversity cognitive complexity was not significantly related to the predictor or outcome variables in this study, further research is warranted to determine the validity of the measure used to assess DCC. The findings in this study support the need for further research exploring training variables that contribute to multicultural counseling outcomes.
ContributorsRigali-Oiler, Marybeth (Author) / Robinson Kurpius, Sharon E (Thesis advisor) / Arciniega, Guillermo M (Committee member) / Nakagawa, Kathryn (Committee member) / Homer, Judith (Committee member) / Arizona State University (Publisher)
Created2013
Description
This study examined the relationship that gender in interaction with interpersonal problem type has with outcome in psychotherapy. A sample of 200 individuals, who sought psychotherapy at a counselor training facility, completed the Outcome Questionnaire-45(OQ-45) and the reduced version of the Inventory of Interpersonal Problems (IIP-32). This study was aimed at examining whether gender (male and female), was related to treatment outcome, and whether this relationship was moderated by two interpersonal distress dimensions: dominance and affiliation. A hierarchical regression analyses was performed and indicated that gender did not predict psychotherapy treatment outcome, and neither dominance nor affiliation were moderators of the relationship between gender and outcome in psychotherapy.
ContributorsHoffmann, Nicole (Author) / Tracey, Terence (Thesis advisor) / Kinnier, Richard (Committee member) / Homer, Judith (Committee member) / Arizona State University (Publisher)
Created2013