Matching Items (186)
Description
Nucleosomes are the basic repetitive unit of eukaryotic chromatin and are responsible for packing DNA inside the nucleus of the cell. They consist of a complex of eight histone proteins (two copies of four proteins H2A, H2B, H3 and H4) around which 147 base pairs of DNA are wrapped in ~1.67 superhelical turns. Although the nucleosomes are stable protein-DNA complexes, they undergo spontaneous conformational changes that occur in an asynchronous fashion. This conformational dynamics, defined by the "site-exposure" model, involves the DNA unwrapping from the protein core and exposing itself transiently before wrapping back. Physiologically, this allows regulatory proteins to bind to their target DNA sites during cellular processes like replication, DNA repair and transcription. Traditional biochemical assays have stablished the equilibrium constants for the accessibility to various sites along the length of the nucleosomal DNA, from its end to the middle of the dyad axis. Using fluorescence correlation spectroscopy (FCS), we have established the position dependent rewrapping rates for nucleosomes. We have also used Monte Carlo simulation methods to analyze the applicability of FRET fluctuation spectroscopy towards conformational dynamics, specifically motivated by nucleosome dynamics. Another important conformational change that is involved in cellular processes is the disassembly of nucleosome into its constituent particles. The exact pathway adopted by nucleosomes is still not clear. We used dual color fluorescence correlation spectroscopy to study the intermediates during nucleosome disassembly induced by changing ionic strength. Studying the nature of nucleosome conformational change and the kinetics is very important in understanding gene expression. The results from this thesis give a quantitative description to the basic unit of the chromatin.
ContributorsGurunathan, Kaushik (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Woodbury, Neal (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
Description
The purpose of our study was to examine the effectiveness of a cycling intervention on body composition in adolescents with Down syndrome (DS). Participants completed one of three interventions over eight consecutive weeks. The interventions were: 1) Voluntary Cycling (VC), in which participants cycled at their self-selected pedaling rate 2) Assisted Cycling (AC), in which the participants' voluntary pedaling rates were assisted with a motor to ensure the maintenance of 80 rpms. 3) No cycling (NC), in which the participants acted as controls. Participants in the AC intervention did not decrease body fat or increase lean body mass however they did maintain these measures during the intervention as compared to the VC and NO participants who increased body fat and decreased lean body mass. These statistics were not exactly as expected nor were they statistically significant. Future research will try to replicate this data with statistically significant values for more cycling adolescents with DS using more randomized intervention groups.
ContributorsBennett, Kristen Leigh (Author) / Ringenbach, Shannon (Thesis director) / Brown, Steven (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This research study examined the effects of assisted cycling using a stationary recumbent bicycle that had an internal motor to help participants pedal at a desired cadence. The participants were either placed in an Assisted Cycling (AC), Voluntary Cycling (VC), or No Cycling (NC) intervention group. Those placed in the AC of VC groups then came to a laboratory setting 3 days a week for 8 weeks to cycle for 30 minutes. This research specifically analyzes the Vineland Adaptive Behavior Scale II to analyze the changes in daily living skills and maladaptive behaviors pre and post the exercise intervention. After analyzing the VABS II scores it was found that those in the VC intervention had statistically significant improvements in maladaptive behaviors. An interpretation of this finding is that the VC intervention had an increased heart rate over the span of the intervention and had a larger power output than those in the AC group. A limitation of this research is that it was a self-reported questionnaire that was given to the caregivers of the participant. The caregivers were not always controlled for, so in some cases two different caregivers were given the questionnaire for a single participant. A suggestion for future research would be to use the participant's mental age versus their chronological age when using the VABS-II and to use the Adaptive Behaviors Assessment System III (ABAS-III).
ContributorsJenkins, Cayla Marie (Author) / Ringenbach, Shannon (Thesis director) / Kulinna, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
Healthy mitochondria are essential for cell survival. Described herein is the synthesis of a family of novel aminoquinone antioxidants designed to alleviate oxidative stress and prevent the impairment of cellular function. In addition, a library of bleomycin disaccharide analogues has also been synthesized to better probe the tumor targeting properties of bleomycin. The first study involves the synthesis of a benzoquinone natural product and analogues that closely resemble the redox core of the natural product geldanamycin. The synthesized 5-amino-3-tridecyl-1,4-benzoquinone antioxidants were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. Some of the analogues synthesized conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations. The biological assays suggest that the modification of the 2-hydroxyl and N-(3-carboxypropyl) groups in the natural product can improve its antioxidant activity and significantly enhance its ability to protect mitochondrial function under conditions of oxidative stress. The second project focused on the synthesis of a library of bleomycin disaccharide-dye conjugates and monitored their cellular uptake by fluorescence microscopy. The studies reveal that the position of the carbamoyl group plays an important role in modulating the cellular uptake of the disaccharide. It also led to the discovery of novel disaccharides with improved tumor selectivity.
ContributorsMathilakathu Madathil, Manikandadas (Author) / Hecht, Sidney M. (Thesis advisor) / Rose, Seth (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher)
Created2013
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
This study examines the effectiveness of two modes of exercise on inhibitory control in adults with Down Syndrome (DS). Thirteen participants attended four sessions: a baseline assessment, an Assisted Cycling Therapy (ACT) session, a Resistance Training (RT) session, and a session of No Training (NT). In the baseline assessment, 1-repetition max (1RM) measurements and voluntary pedal rate measurements were taken. In the resistance training session, the leg press, chest press, seated row, leg curl, shoulder press, and latissimus pulldown were performed. In the cycling intervention, the participant completed 30 minutes of cycling. The Erikson Flanker task was administered prior to each session (i.e., pretest) and after the intervention (i.e., post-test). The results were somewhat consistent with the hypothesis that inhibition time improved more following RT and ACT than NT. there was also a significant difference between ACT and NT. Additionally, it was hypothesized that all measures would improve following each acute exercise intervention, but the most significant improvements were seen following ACT. In conclusion, an acute session of ACT demonstrated a significant trend towards improvements in inhibitory control in adults with DS which we interpreted using a model of neural changes.
ContributorsHayes, Claire (Author) / Ringenbach, Shannon (Thesis director) / Arnold, Nate (Committee member) / Rand, Miya (Committee member) / Edson College of Nursing and Health Innovation (Contributor) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The field of biomedical research relies on the knowledge of binding interactions between various proteins of interest to create novel molecular targets for therapeutic purposes. While many of these interactions remain a mystery, knowledge of these properties and interactions could have significant medical applications in terms of understanding cell signaling and immunological defenses. Furthermore, there is evidence that machine learning and peptide microarrays can be used to make reliable predictions of where proteins could interact with each other without the definitive knowledge of the interactions. In this case, a neural network was used to predict the unknown binding interactions of TNFR2 onto LT-ɑ and TRAF2, and PD-L1 onto CD80, based off of the binding data from a sampling of protein-peptide interactions on a microarray. The accuracy and reliability of these predictions would rely on future research to confirm the interactions of these proteins, but the knowledge from these methods and predictions could have a future impact with regards to rational and structure-based drug design.
ContributorsPoweleit, Andrew Michael (Author) / Woodbury, Neal (Thesis director) / Diehnelt, Chris (Committee member) / Chiu, Po-Lin (Committee member) / School of Molecular Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The purpose of this study is to first investigate the role of political socialization on young men and women and what motivates them to become politically active and make the ultimate decision to run for elected office. These effects include parental attitudes, exposure to political shows and news sources, participation in voluntary organizations, and overall community involvement. After understanding these direct and indirect effects of political socialization, I can attempt to explain the causes for the gender gap in political ambition \u2014 meaning that significantly more men are running for elected office compared to women.
ContributorsOsgood, Shannon Marie (Author) / Woodall, Gina (Thesis director) / Herrera, Richard (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Public Affairs (Contributor) / School of Politics and Global Studies (Contributor)
Created2015-05
Description
This study examines cognitive planning in adolescents with Down syndrome (DS) following an 8-week assisted cycling therapy intervention. Forty-three participants were randomly assigned to assisted cycling (AC) (i.e., at least 30% faster than self-selected cadence accomplished by a motor), voluntary cycling (VC) (self-selected cadence), and no cycling (NC) control group. Both AC and VC rode a stationary bicycle three times/week, 30 minutes/session, for eight weeks in duration. Participants completed cognitive testing that assessed cognitive planning at the beginning (i.e., pretest) and end (i.e., posttest) of the 8-week intervention. Consistent with our hypothesis, the results showed that cognitive planning improved following eight weeks of cycling for the AC group. The same results were not seen for individuals in the VC or NC groups. Our results suggest that assisted cycling therapy may induce permanent changes in the prefrontal cortex in adolescents with DS.
ContributorsMillar, Kelsey Leann (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This study examines the effectiveness of two modes of exercise on depression in adolescents with Down syndrome (DS). Thirty nine participants were randomly divided into a voluntary cycling group (VC) (i.e., self-selected cadence), an assisted cycling group (AC) (i.e., at least 30% faster than self-selected cadence accomplished by a motor), or a no exercise group (NC). In each cycling intervention the participant completed 30 minute cycling sessions, three times per week for a total of eight weeks. The Children's Depression Inventory II was administered prior to cycling (i.e., pretest) and after the eight week intervention (i.e., posttest). Although the data did not reach conventional levels of statistical significance, the results of the study demonstrated partial support for our hypothesis that adolescents with DS showed improvements in depression as measured by the Children's Depression Inventory II following assisted cycling, but not following eight weeks of voluntary cycling. In other words, eight weeks of moderate AC exercise demonstrated a trend for improved depression in adolescents with DS.
ContributorsMcgownd, Shana Leah (Author) / Ringenbach, Shannon (Thesis director) / Youngstedt, Shawn (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05