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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
This project sheds light on trombonist Andy Martin's improvisation and provides tools for further learning. A biographical sketch gives background on Martin, establishing him as a newer jazz master. Through the transcription and analysis of nine improvised solos, Martin's improvisational voice and vocabulary is deciphered and presented as a series of seven thematic hooks. These patterns, rhythms, and gestures are described, analyzed, and presented as examples of how each is used in the solos. The hooks are also set as application exercises for learning jazz style and improvisation. These exercises demonstrate how to use Martin's hooks as a means for furthering one's own improvisation. A full method for successful transcription is also presented, along with the printed transcriptions and their accompanying information sheets.
ContributorsWilkinson, Michael Scott (Author) / Ericson, John (Thesis advisor) / Kocour, Michael (Committee member) / Solis, Theodore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Jazz continues, into its second century, as one of the most important musics taught in public middle and high schools. Even so, research related to how students learn, especially in their earliest interactions with jazz culture, is limited. Weaving together interviews and observations of junior and senior high school jazz players and teachers, private studio instructors, current university students majoring in jazz, and university and college jazz faculty, I developed a composite sketch of a secondary school student learning to play jazz. Using arts-based educational research methods, including the use of narrative inquiry and literary non-fiction, the status of current jazz education and the experiences by novice jazz learners is explored. What emerges is a complex story of students and teachers negotiating the landscape of jazz in and out of early twenty-first century public schools. Suggestions for enhancing jazz experiences for all stakeholders follow, focusing on access and the preparation of future jazz teachers.
ContributorsKelly, Keith B (Author) / Stauffer, Sandra (Thesis advisor) / Tobias, Evan (Committee member) / Kocour, Michael (Committee member) / Sullivan, Jill (Committee member) / Schmidt, Margaret (Committee member) / Arizona State University (Publisher)
Created2013
Description
Concerto for Piano and Chamber Orchestra was conceived in February of 2013, and conceptually it is my attempt to fuse personal expressions of jazz and classical music into one fully realized statement. It is a three movement work (fast, slow, fast) for 2 fl., 2 ob., 2 cl., bsn., 2 hrn., 2 tpt., tbn., pno., perc., str. (6,4,2,2,1). The work is approximately 27 minutes in duration. The first movement of the Concerto is written in a fluid sonata form. A fugato begins where the second theme would normally appear, and the second theme does not fully appear until near the end of the solo piano section. The result is that the second theme when finally revealed is so reminiscent of the history of jazz and classical synthesis that it does not sound completely new, and in fact is a return of something that was heard before, but only hinted at in this piece. The second movement is a kind of deconstructive set of variations, with a specific theme and harmonic pattern implied throughout the movement. However, the full theme is not disclosed until the final variation. The variations are interrupted by moments of pure rhythmic music, containing harmony made up of major chords with an added fourth, defying resolution, and dissolving each time back into a new variation. The third movement is in rondo form, using rhythmic and harmonic influences from jazz. The percussion plays a substantial role in this movement, acting as a counterpoint to the piano part throughout. This movement and the piece concludes with an extended coda, inspired indirectly by the simple complexities of an improvisational piano solo, building in complexity as the concerto draws to a close.
ContributorsSneider, Elliot (Author) / Rogers, Rodney (Thesis advisor) / DeMars, James (Committee member) / Hackbarth, Glenn (Committee member) / Solis, Theodore (Committee member) / Arizona State University (Publisher)
Created2013
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
Telomerase enzyme is a truly remarkable enzyme specialized for the addition of short, highly repetitive DNA sequences onto linear eukaryotic chromosome ends. The telomerase enzyme functions as a ribonucleoprotein, minimally composed of the highly conserved catalytic telomerase reverse transcriptase and essential telomerase RNA component containing an internalized short template region within the vastly larger non-coding RNA. Even among closely related groups of species, telomerase RNA is astonishingly divergent in sequence, length, and secondary structure. This massive disparity is highly prohibitive for telomerase RNA identification from previously unexplored groups of species, which is fundamental for secondary structure determination. Combined biochemical enrichment and computational screening methods were employed for the discovery of numerous telomerase RNAs from the poorly characterized echinoderm lineage. This resulted in the revelation that--while closely related to the vertebrate lineage and grossly resembling vertebrate telomerase RNA--the echinoderm telomerase RNA central domain varies extensively in structure and sequence, diverging even within echinoderms amongst sea urchins and brittle stars. Furthermore, the origins of telomerase RNA within the eukaryotic lineage have remained a persistent mystery. The ancient Trypanosoma telomerase RNA was previously identified, however, a functionally verified secondary structure remained elusive. Synthetic Trypanosoma telomerase was generated for molecular dissection of Trypanosoma telomerase RNA revealing two RNA domains functionally equivalent to those found in known telomerase RNAs, yet structurally distinct. This work demonstrates that telomerase RNA is uncommonly divergent in gross architecture, while retaining critical universal elements.
ContributorsPodlevsky, Joshua (Author) / Chen, Julian (Thesis advisor) / Mangone, Marco (Committee member) / Kusumi, Kenro (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2015
Description
This multiple-case study addresses the nature of the out-of-school musical engagements of four undergraduate students who were enrolled as jazz studies majors in a large school of music in the U.S. southwest. It concerns what they did musically when they were outside of school, why they did what they did, what experiences they said they learned from, and how their out-of-school engagements related to their in-school curriculum. Research on jazz education, informal learning practices in music, and the in-school and out-of-school experiences of students informed this study. Data were generated through observation, interviews, video blogs (vlogs), and SMS text messages.
Analysis of data revealed that participants engaged with music when outside of school by practicing, teaching, gigging, recording, playing music with others, attending live musical performances, socializing with other musicians, listening, and engaging with non-jazz musical styles (aside from listening). They engaged with music because of: 1) the love of music, 2) the desire for musical excellence, 3) financial considerations, 4) the aspiration to affect others positively with music, and 5) the connection with other musicians. Participants indicated that they learned by practicing, listening to recordings, attending live performances, playing paid engagements, socializing, teaching, and reading. In-school and out-of-school experience and learning had substantial but not complete overlap.
The study implies that a balance between in-school and out-of-school musical experience may help undergraduate jazz studies students to maximize their overall musical learning. It also suggests that at least some jazz studies majors are fluent in a wide variety of music learning practices that make them versatile, flexible, and employable musicians. Further implications are provided for undergraduate jazz students as well as collegiate jazz educators, the music education profession, and schools of music. Additional implications concern future research and the characterization of jazz study in academia.
Analysis of data revealed that participants engaged with music when outside of school by practicing, teaching, gigging, recording, playing music with others, attending live musical performances, socializing with other musicians, listening, and engaging with non-jazz musical styles (aside from listening). They engaged with music because of: 1) the love of music, 2) the desire for musical excellence, 3) financial considerations, 4) the aspiration to affect others positively with music, and 5) the connection with other musicians. Participants indicated that they learned by practicing, listening to recordings, attending live performances, playing paid engagements, socializing, teaching, and reading. In-school and out-of-school experience and learning had substantial but not complete overlap.
The study implies that a balance between in-school and out-of-school musical experience may help undergraduate jazz studies students to maximize their overall musical learning. It also suggests that at least some jazz studies majors are fluent in a wide variety of music learning practices that make them versatile, flexible, and employable musicians. Further implications are provided for undergraduate jazz students as well as collegiate jazz educators, the music education profession, and schools of music. Additional implications concern future research and the characterization of jazz study in academia.
ContributorsLibman, Jeffrey B (Author) / Tobias, Evan (Thesis advisor) / Kocour, Michael (Committee member) / Schmidt, Margaret (Committee member) / Solis, Theodore (Committee member) / Stauffer, Sandra (Committee member) / Arizona State University (Publisher)
Created2014
Description
The study of artist transcriptions is an effective vehicle for assimilating the language and style of jazz. Pairing transcriptions with historical context provides further insight into the back story of the artists' life and method. Innovators are often the subject of published studies of this kind, but transcriptions of plunger-mute master Al Grey have been overlooked. This document fills that void, combining historical context with thirteen transcriptions of Grey's trombone features and improvisations. Selection of transcribed materials was based on an examination of historically significant solos in Al Grey's fifty-five-year career. The results are a series of open-horn and plunger solos that showcase Grey's sound, technical brilliance, and wide range of dynamics and articulation. This collection includes performances from a mix of widely available and obscure recordings, the majority coming from engagements with the Count Basie Orchestra. Methods learned from the study of Al Grey's book Plunger Techniques were vital in the realization of his work. The digital transcription software Amazing Slow Downer by Roni Music aided in deciphering some of Grey's more complicated passages and, with octave displacement, helped bring previously inaudible moments to the foreground.
ContributorsHopkins, Charles E (Author) / Pilafian, Sam (Thesis advisor) / Stauffer, Sandra (Committee member) / Solís, Ted (Committee member) / Ericson, John (Committee member) / Kocour, Michael (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex.
ContributorsLi, Yang (Author) / Chen, Julian Jl (Thesis advisor) / Yan, Hao (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
This study examines the experiences of participants enrolled in an online community college jazz history course. I surveyed the participants before the course began and observed them in the online space through the duration of the course. Six students also participated in interviews during and after the course. Coded data from the interviews, surveys, and recorded discussion posts and journal entries provided evidence about the nature of interaction and engagement in learning in an online environment. I looked for evidence either supporting or detracting from a democratic online learning environment, concentrating on the categories of student engagement, freedom of expression, and accessibility. The data suggested that the participants' behaviors in and abilities to navigate the online class were influenced by their pre-existing native media habits. Participants' reasons for enrolling in the online course, which included convenience and schedule flexibility, informed their actions and behaviors in the class. Analysis revealed that perceived positive student engagement did not contribute to a democratic learning environment but rather to an easy, convenient experience in the online class. Finally, the data indicated that participants' behaviors in their future lives would not be affected by the online class in that their learning experiences were not potent enough to alter or inform their behavior in society. As online classes gain popularity, the ability of these classes to provide meaningful learning experiences must be questioned. Students in this online jazz history class presented, at times, a façade of participation and community building but demonstrated a lack of sincerity and interest in the course. The learning environment supported accessibility and freedom of expression to an extent, but students' engagement with their peers was limited. Overall, this study found a need for more research into the quality of online classes as learning platforms that support democracy, student-to-student interaction, and community building.
ContributorsHunter, Robert W. (Author) / Stauffer, Sandra L (Thesis advisor) / Tobias, Evan (Thesis advisor) / Bush, Jeffrey (Committee member) / Kocour, Michael (Committee member) / Pilafian, Sam (Committee member) / Arizona State University (Publisher)
Created2011