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- Genre: Masters Thesis
Description
It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be linked with dysfunctional complexes in the mitochondrial respiratory chain, increased oxidative stress, and potential cell death. Increased understanding of the pathophysiology of this disease has enabled the development of various therapeutic strategies aimed at restoring mitochondrial respiration. This thesis contains an analysis of the biological activity of several classes of antioxidants against oxidative stress induced by diethyl maleate in Friedreich's Ataxia lymphocytes and CEM leukemia cells. Analogues of vitamin E α-tocopherol have been shown to protect cells under oxidative stress. However, these same analogues show various levels of inhibition towards the electron transport chain complex I. Bicyclic pyridinols containing a ten carbon substituent provided favorable cytoprotection. N-hydroxy-4-pyridone compounds were observed to provide little protection. Similarly, analogues of CoQ10 in the form of pyridinol and pyrimidinol compounds also preserved cell viability at low concentrations.
ContributorsJaruvangsanti, Jennifer (Author) / Hecht, Sidney (Thesis advisor) / Woodbury, Neal (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cocaine induces long-lasting changes in mesolimbic ‘reward’ circuits of the brain after cessation of use. These lingering changes include the neuronal plasticity that is thought to underlie the chronic relapsing nature of substance use disorders. Genes involved in neuronal plasticity also encode circular RNAs (circRNAs), which are stable, non-coding RNAs formed through the back-splicing of pre-mRNA. The Homer1 gene family, which encodes proteins associated with cocaine-induced plasticity, also encodes circHomer1. Based on preliminary evidence from shows cocaine-regulated changes in the ratio of circHomer1 and Homer1b mRNA in the nucleus accumbens (NAc), this study examined the relationship between circHomer1 and incentive motivation for cocaine by using different lengths of abstinence to vary the degree of motivation. Male and female rats were trained to self-administer cocaine (0.75 mg/kg/infusion, IV) or received a yoked saline infusion. Rats proceeded on an increasingly more difficult variable ratio schedule of lever pressing until they reached a variable ratio 5 schedule, which requires an average of 5 lever presses, and light and tone cues were delivered with the drug infusions. Rats were then tested for cocaine-seeking behavior in response to cue presentations without drug delivery either 1 or 21 days after their last self-administration session. They were sacrificed immediately after and circHomer1 and Homer1b expression was then measured from homogenate and synaptosomal fractions of NAc shell using RT-qPCR. Lever pressing during the cue reactivity test increased from 1 to 21 days of abstinence as expected. Results showed no group differences in synaptic circHomer1 expression, however, total circHomer1 expression was downregulated in 21d rats compared to controls. Lack of change in synaptic circHomer1 was likely due to trends toward different temporal changes in males versus females. Total Homer1b expression was higher in females, although there was no effect of cocaine abstinence. Further research investigating the time course of circHomer1 and Homer1b expression is warranted based on the inverse relationship between total circHomer1and cocaine-seeking behavior observed in this study.
ContributorsJohnson, Michael Christian (Author) / Neisewander, Janet L (Thesis advisor) / Perrone-Bizzozero, Nora (Thesis advisor) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
MicroRNAs (miRNAs) are 17-22 nucleotide non-coding RNAs that regulate gene expression by targeting non-complementary elements in the 3’ untranslated regions (3’UTRs) of mRNAs. miRNAs, which form complex networks of interaction that differ by tissue and developmental stage, display conservation in their function across metazoan species. Yet much remains unknown regarding their biogenesis, localization, strand selection, and their absolute abundance due to the difficulty of detecting and amplifying such small molecules. Here, I used an updated HT qPCR-based methodology to follow miRNA expression of 5p and 3p strands for all 190 C. elegans miRNAs described in miRBase throughout all six developmental stages in triplicates (total of 9,708 experiments), and studied their expression levels, tissue localization, and the rules underlying miRNA strand selection. My study validated previous findings and identified novel, conserved patterns of miRNA strand expression throughout C. elegans development, which at times correlate with previously observed developmental phenotypes. Additionally, my results highlighted novel structural principles underlying strand selection, which can be applied to higher metazoans.
Though optimized for use in C. elegans, this method can be easily adapted to other eukaryotic systems, allowing for more scalable quantitative investigation of miRNA biology and/or miRNA diagnostics.
ContributorsMeadows, Dalton Alexander (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Murugan, Vel (Committee member) / Wilson-Rawls, Jeanne (Committee member) / Arizona State University (Publisher)
Created2023
Description
Education through field exploration is fundamental in geoscience. But not all students enjoy equal access to field-based learning because of time, cost, distance, ability, and safety constraints. At the same time, technological advances afford ever more immersive, rich, and student-centered virtual field experiences. Virtual field trips may be the only practical options for most students to explore pedagogically rich but inaccessible places. A mixed-methods research project was conducted on an introductory and an advanced geology class to explore the implications of learning outcomes of in-person and virtual field-based instruction at Grand Canyon National Park. The study incorporated the Great Unconformity in the Grand Canyon, a 1.2 billion year break in the rock record; the Trail of Time, an interpretive walking timeline; and two immersive, interactive virtual field trips (iVFTs). The in-person field trip (ipFT) groups collectively explored the canyon and took an instructor-guided inquiry hike along the interpretive Trail of Time from rim level, while iVFT students individually explored the canyon and took a guided-inquiry virtual tour of Grand Canyon geology from river level. High-resolution 360° spherical images anchor the iVFTs and serve as a framework for programmed overlays that enable interactivity and allow the iVFT to provide feedback in response to student actions. Students in both modalities received pre- and post-trip Positive and Negative Affect Schedules (PANAS). The iVFT students recorded pre- to post-trip increases in positive affect (PA) scores and decreases in negative (NA) affect scores, representing an affective state conducive to learning. Pre- to post-trip mean scores on concept sketches used to assess visualization and geological knowledge increased for both classes and modalities. However, the iVFT pre- to post-trip increases were three times greater (statistically significant) than the ipFT gains. Both iVFT and ipFT students scored 92-98% on guided-inquiry worksheets completed during the trips, signifying both met learning outcomes. Virtual field trips do not trump traditional in-person field work, but they can meet and/or exceed similar learning objectives and may replace an inaccessible or impractical in-person field trip.
ContributorsRuberto, Thomas (Author) / Semken, Steve (Thesis advisor) / Anbar, Ariel (Committee member) / Brownell, Sara (Committee member) / Arizona State University (Publisher)
Created2018
Description
Calls for changes in science education over the last several decades have contributed to a changing landscape of undergraduate life science education. As opposed to simply lecturing at students and expecting them to recite science facts, there has been a strong push to make systemic changes so that students not only know pertinent science content, but also walk away with critical science process skills. There have been suggestions to create environments that focus on goals such as evaluating scientific evidence and explanations, understanding the development of scientific knowledge, and participating in scientific practice and discourse. As a part of the call for increases in student participation in science practice, we’ve seen suggestions to increase student exposure to the tools, techniques, and published research within various science fields. The use of primary scientific literature in the classroom is documented as being a tool to introduce students to the nature of scientific reasoning, experimental design, and knowledge creation and transformation. Many of the current studies on primary scientific literature in undergraduate courses report on intensive course designs in which students interact with the material with very specific goals, as outlined by the authors and researchers. We know less about the practices that take place in typical undergraduate settings. This exploratory study looks at information provided by a national sample of faculty that alludes to what sort of practices are taking place and the reasoning for doing so. Through analysis of both closed-ended and open-ended survey questions we have found that faculty are engaging students with primary scientific literature for many reasons and in a variety of ways. We have also attempted to characterize the way in which faculty view the body of scientific literature, as members of the research community. We discuss the implications of faculty views on the utility and value of the body of scientific literature. We also argue that those perceptions inform how the material is used in the undergraduate classroom.
ContributorsWagoner, Nevada (Author) / Brownell, Sara (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2016