Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Displaying 1 - 10 of 168
Description
Most people are experts in some area of information; however, they may not be knowledgeable about other closely related areas. How knowledge is generalized to hierarchically related categories was explored. Past work has found little to no generalization to categories closely related to learned categories. These results do not fit well with other work focusing on attention during and after category learning. The current work attempted to merge these two areas of by creating a category structure with the best chance to detect generalization. Participants learned order level bird categories and family level wading bird categories. Then participants completed multiple measures to test generalization to old wading bird categories, new wading bird categories, owl and raptor categories, and lizard categories. As expected, the generalization measures converged on a single overall pattern of generalization. No generalization was found, except for already learned categories. This pattern fits well with past work on generalization within a hierarchy, but do not fit well with theories of dimensional attention. Reasons why these findings do not match are discussed, as well as directions for future research.
ContributorsLancaster, Matthew E (Author) / Homa, Donald (Thesis advisor) / Glenberg, Arthur (Committee member) / Chi, Michelene (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2013
Description
There is a lack of music therapy services for college students who have problems with depression and/or anxiety. Even among universities and colleges that offer music therapy degrees, there are no known programs offering music therapy to the institution's students. Female college students are particularly vulnerable to depression and anxiety symptoms compared to their male counterparts. Many students who experience mental health problems do not receive treatment, because of lack of knowledge, lack of services, or refusal of treatment. Music therapy is proposed as a reliable and valid complement or even an alternative to traditional counseling and pharmacotherapy because of the appeal of music to young women and the potential for a music therapy group to help isolated students form supportive networks. The present study recruited 14 female university students to participate in a randomized controlled trial of short-term group music therapy to address symptoms of depression and anxiety. The students were randomly divided into either the treatment group or the control group. Over 4 weeks, each group completed surveys related to depression and anxiety. Results indicate that the treatment group's depression and anxiety scores gradually decreased over the span of the treatment protocol. The control group showed either maintenance or slight worsening of depression and anxiety scores. Although none of the results were statistically significant, the general trend indicates that group music therapy was beneficial for the students. A qualitative analysis was also conducted for the treatment group. Common themes were financial concerns, relationship problems, loneliness, and time management/academic stress. All participants indicated that they benefited from the sessions. The group progressed in its cohesion and the participants bonded to the extent that they formed a supportive network which lasted beyond the end of the protocol. The results of this study are by no means conclusive, but do indicate that colleges with music therapy degree programs should consider adding music therapy services for their general student bodies.
ContributorsAshton, Barbara (Author) / Crowe, Barbara J. (Thesis advisor) / Rio, Robin (Committee member) / Davis, Mary (Committee member) / Arizona State University (Publisher)
Created2013
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in the loss of lower body muscle function. SMA is the second leading genetic cause of death in infants and arises from the loss of the Survival of Motor Neuron (SMN) protein. SMN is produced by two genes, smn1 and smn2, that are identical with the exception of a C to T conversion in exon 7 of the smn2 gene. SMA patients lacking the smn1 gene, rely on smn2 for production of SMN. Due to an alternative splicing event, smn2 primarily encodes a non-functional SMN lacking exon 7 (SMN D7) as well as a low amount of functional full-length SMN (SMN WT). SMN WT is ubiquitously expressed in all cell types, and it remains unclear how low levels of SMN WT in motor neurons lead to motor neuron degradation and SMA. SMN and its associated proteins, Gemin2-8 and Unrip, make up a large dynamic complex that functions to assemble ribonucleoproteins. The aim of this project was to characterize the interactions of the core SMN-Gemin2 complex, and to identify differences between SMN WT and SMN D7. SMN and Gemin2 proteins were expressed, purified and characterized via size exclusion chromatography. A stable N-terminal deleted Gemin2 protein (N45-G2) was characterized. The SMN WT expression system was optimized resulting in a 10-fold increase of protein expression. Lastly, the oligomeric states of SMN and SMN bound to Gemin2 were determined. SMN WT formed a mixture of oligomeric states, while SMN D7 did not. Both SMN WT and D7 bound to Gemin2 with a one-to-one ratio forming a heterodimer and several higher-order oligomeric states. The SMN WT-Gemin2 complex favored high molecular weight oligomers whereas the SMN D7-Gemin2 complex formed low molecular weight oligomers. These results indicate that the SMA mutant protein, SMN D7, was still able to associate with Gemin2, but was not able to form higher-order oligomeric complexes. The observed multiple oligomerization states of SMN and SMN bound to Gemin2 may play a crucial role in regulating one or several functions of the SMN protein. The inability of SMN D7 to form higher-order oligomers may inhibit or alter those functions leading to the SMA disease phenotype.
ContributorsNiday, Tracy (Author) / Allen, James P. (Thesis advisor) / Wachter, Rebekka (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2012
Description
This thesis explores a wide array of topics related to the protein folding problem, ranging from the folding mechanism, ab initio structure prediction and protein design, to the mechanism of protein functional evolution, using multi-scale approaches. To investigate the role of native topology on folding mechanism, the native topology is dissected into non-local and local contacts. The number of non-local contacts and non-local contact orders are both negatively correlated with folding rates, suggesting that the non-local contacts dominate the barrier-crossing process. However, local contact orders show positive correlation with folding rates, indicating the role of a diffusive search in the denatured basin. Additionally, the folding rate distribution of E. coli and Yeast proteomes are predicted from native topology. The distribution is fitted well by a diffusion-drift population model and also directly compared with experimentally measured half life. The results indicate that proteome folding kinetics is limited by protein half life. The crucial role of local contacts in protein folding is further explored by the simulations of WW domains using Zipping and Assembly Method. The correct formation of N-terminal β-turn turns out important for the folding of WW domains. A classification model based on contact probabilities of five critical local contacts is constructed to predict the foldability of WW domains with 81% accuracy. By introducing mutations to stabilize those critical local contacts, a new protein design approach is developed to re-design the unfoldable WW domains and make them foldable. After folding, proteins exhibit inherent conformational dynamics to be functional. Using molecular dynamics simulations in conjunction with Perturbation Response Scanning, it is demonstrated that the divergence of functions can occur through the modification of conformational dynamics within existing fold for β-lactmases and GFP-like proteins: i) the modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate, while the resurrected ancient lactamases indicate enhanced active-site flexibility, which likely allows for the binding and subsequent degradation of different antibiotic molecules; ii) the chromophore and attached peptides of photocoversion-competent GFP-like protein exhibits higher flexibility than the photocoversion-incompetent one, consistent with the evolution of photocoversion capacity.
ContributorsZou, Taisong (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Woodbury, Neal W (Committee member) / Vaiana, Sara M (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Interactions driving the collapse of islet amyloid polypeptide: implications for amyloid aggregation
Description
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-residue intrinsically disordered hormone involved in glucose regulation and gastric emptying. The aggregation of hIAPP into amyloid fibrils is believed to play a causal role in type 2 diabetes. To date, not much is known about the monomeric state of hIAPP or how it undergoes an irreversible transformation from disordered peptide to insoluble aggregate. IAPP contains a highly conserved disulfide bond that restricts hIAPP(1-8) into a short ring-like structure: N_loop. Removal or chemical reduction of N_loop not only prevents cell response upon binding to the CGRP receptor, but also alters the mass per length distribution of hIAPP fibers and the kinetics of fibril formation. The mechanism by which N_loop affects hIAPP aggregation is not yet understood, but is important for rationalizing kinetics and developing potential inhibitors. By measuring end-to-end contact formation rates, Vaiana et al. showed that N_loop induces collapsed states in IAPP monomers, implying attractive interactions between N_loop and other regions of the disordered polypeptide chain . We show that in addition to being involved in intra-protein interactions, the N_loop is involved in inter-protein interactions, which lead to the formation of extremely long and stable β-turn fibers. These non-amyloid fibers are present in the 10 μM concentration range, under the same solution conditions in which hIAPP forms amyloid fibers. We discuss the effect of peptide cyclization on both intra- and inter-protein interactions, and its possible implications for aggregation. Our findings indicate a potential role of N_loop-N_loop interactions in hIAPP aggregation, which has not previously been explored. Though our findings suggest that N_loop plays an important role in the pathway of amyloid formation, other naturally occurring IAPP variants that contain this structural feature are incapable of forming amyloids. For example, hIAPP readily forms amyloid fibrils in vitro, whereas the rat variant (rIAPP), differing by six amino acids, does not. In addition to being highly soluble, rIAPP is an effective inhibitor of hIAPP fibril formation . Both of these properties have been attributed to rIAPP's three proline residues: A25P, S28P and S29P. Single proline mutants of hIAPP have also been shown to kinetically inhibit hIAPP fibril formation. Because of their intrinsic dihedral angle preferences, prolines are expected to affect conformational ensembles of intrinsically disordered proteins. The specific effect of proline substitutions on IAPP structure and dynamics has not yet been explored, as the detection of such properties is experimentally challenging due to the low molecular weight, fast reconfiguration times, and very low solubility of IAPP peptides. High-resolution techniques able to measure tertiary contact formations are needed to address this issue. We employ a nanosecond laser spectroscopy technique to measure end-to-end contact formation rates in IAPP mutants. We explore the proline substitutions in IAPP and quantify their effects in terms of intrinsic chain stiffness. We find that the three proline mutations found in rIAPP increase chain stiffness. Interestingly, we also find that residue R18 plays an important role in rIAPP's unique chain stiffness and, together with the proline residues, is a determinant for its non-amyloidogenic properties. We discuss the implications of our findings on the role of prolines in IDPs.
ContributorsCope, Stephanie M (Author) / Vaiana, Sara M (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Ros, Robert (Committee member) / Lindsay, Stuart M (Committee member) / Ozkan, Sefika B (Committee member) / Arizona State University (Publisher)
Created2013
Description
Sometimes difficult life events challenge our existing resources in such a way that routinized responses are inadequate to handle the challenge. Some individuals will persist in habitual, automatic behavior, regardless of environmental cues that indicate a mismatch between coping strategy and the demands of the stressor. Other individuals will marshal adaptive resources to construct new courses of action and reconceptualize the problem, associated goals and/or values. A mixed methods approach was used to describe and operationalize cognitive shift, a relatively unexplored construct in existing literature. The study was conducted using secondary data from a parent multi-year cross-sectional study of resilience with eight hundred mid-aged adults from the Phoenix metro area. Semi-structured telephone interviews were analyzed using a purposive sample (n=136) chosen by type of life event. Participants' beliefs, assumptions, and experiences were examined to understand how they shaped adaptation to adversity. An adaptive mechanism, "cognitive shift," was theorized as the transition from automatic coping to effortful cognitive processes aimed at novel resolution of issues. Aims included understanding when and how cognitive shift emerges and manifests. Cognitive shift was scored as a binary variable and triangulated through correlational and logistic regression analyses. Interaction effects revealed that positive personality attributes influence cognitive shift most when people suffered early adversity. This finding indicates that a certain complexity, self-awareness and flexibility of mind may lead to a greater capacity to find meaning in adversity. This work bridges an acknowledged gap in literature and provides new insights into resilience.
ContributorsRivers, Crystal T (Author) / Zautra, Alex (Thesis advisor) / Davis, Mary (Committee member) / Kurpius, Sharon (Committee member) / Arizona State University (Publisher)
Created2014
Description
Recognition memory was investigated for naturalistic dynamic scenes. Although visual recognition for static objects and scenes has been investigated previously and found to be extremely robust in terms of fidelity and retention, visual recognition for dynamic scenes has received much less attention. In four experiments, participants view a number of clips from novel films and are then tasked to complete a recognition test containing frames from the previously viewed films and difficult foil frames. Recognition performance is good when foils are taken from other parts of the same film (Experiment 1), but degrades greatly when foils are taken from unseen gaps from within the viewed footage (Experiments 3 and 4). Removing all non-target frames had a serious effect on recognition performance (Experiment 2). Across all experiments, presenting the films as a random series of clips seemed to have no effect on recognition performance. Patterns of accuracy and response latency in Experiments 3 and 4 appear to be a result of a serial-search process. It is concluded that visual representations of dynamic scenes may be stored as units of events, and participant's old
ew judgments of individual frames were better characterized by a cued-recall paradigm than traditional recognition judgments.
ew judgments of individual frames were better characterized by a cued-recall paradigm than traditional recognition judgments.
ContributorsFerguson, Ryan (Author) / Homa, Donald (Thesis advisor) / Goldinger, Stephen (Committee member) / Glenberg, Arthur (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2014
Description
Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this, telomerase uses a small section of its integral RNA subunit (TR) to reiteratively copy a short, canonically 6-nt, sequence repeatedly in a processive manner using a complex and currently poorly understood mechanism of template translocation to stop nucleotide addition, regenerate its template, and then synthesize a new repeat. In this study, several novel interactions between the telomerase protein and RNA components along with the DNA substrate are identified and characterized which come together to allow active telomerase repeat addition. First, this study shows that the sequence of the RNA/DNA duplex holds a unique, single nucleotide signal which pauses DNA synthesis at the end of the canonical template sequence. Further characterization of this sequence dependent pause signal reveals that the template sequence alone can produce telomerase products with the characteristic 6-nt pattern, but also works cooperatively with another RNA structural element for proper template boundary definition. Finally, mutational analysis is used on several regions of the protein and RNA components of telomerase to identify crucial determinates of telomerase assembly and processive repeat synthesis. Together, these results shed new light on how telomerase coordinates its complex catalytic cycle.
ContributorsBrown, Andrew F (Author) / Chen, Julian J. L. (Thesis advisor) / Jones, Anne (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Description
Categories are often defined by rules regarding their features. These rules may be intensely complex yet, despite the complexity of these rules, we are often able to learn them with sufficient practice. A possible explanation for how we arrive at consistent category judgments despite these difficulties would be that we may define these complex categories such as chairs, tables, or stairs by understanding the simpler rules defined by potential interactions with these objects. This concept, called grounding, allows for the learning and transfer of complex categorization rules if said rules are capable of being expressed in a more simple fashion by virtue of meaningful physical interactions. The present experiment tested this hypothesis by having participants engage in either a Rule Based (RB) or Information Integration (II) categorization task with instructions to engage with the stimuli in either a non-interactive or interactive fashion. If participants were capable of grounding the categories, which were defined in the II task with a complex visual rule, to a simpler interactive rule, then participants with interactive instructions should outperform participants with non-interactive instructions. Results indicated that physical interaction with stimuli had a marginally beneficial effect on category learning, but this effect seemed most prevalent in participants were engaged in an II task.
ContributorsCrawford, Thomas (Author) / Homa, Donald (Thesis advisor) / Glenberg, Arthur (Committee member) / McBeath, Michael (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2014
Description
ABSTRACT
Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.
In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.
In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.
Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.
In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.
In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.
ContributorsMorales Betanzos, Carlos (Author) / LaBaer, Joshua (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014