Matching Items (120)
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
Purpose: To examine: (1) whether Non-Hispanic Blacks (NHB) and Non-Hispanic Whites (NHW) with diagnosed arthritis differed in self-reported physical activity (PA) levels, (2) if NHB and NHW with arthritis differed on potential correlates of PA based on the Social Ecological Model (Mcleroy et al., 1988), and (3) if PA participation varied by race/ethnicity after controlling for age, gender, education, and BMI. Methods: This study was a secondary data analysis of data collected from 2006-2008 in Chicago, IL as part of the Midwest Roybal Center for Health Promotion. Bivariate analyses were used to assess potential differences between race in meeting either ACR or ACSM PA guidelines. Comparisons by race between potential socio-demographic correlates and meeting physical activity guidelines were assessed using Chi-squares. Potential differences by race in psychosocial, arthritis, and health-related and environmental correlates were assessed using T-tests. Finally, logistic regression analyses were used to examine if race was still associated with PA after controlling for socio-demographic characteristics. Results: A greater proportion of NHW (68.1% and 35.3%) than NHB (46.5% and 20.9%) met both the arthritis-specific and the American College of Sports Medicine (ACSM) recommendations for physical activity, respectively. NHB had significantly lower self-efficacy for exercise and reported greater impairments in physical function compared to NHW. Likewise, NHB reported more crime and less aesthetics within their neighborhood. NHW were 2.56 times more likely to meet arthritis-specific PA guidelines than NHB after controlling for age, gender, education, marital status, and BMI. In contrast, after controlling for sociodemographic characteristics, age and gender were the only significant predictors of meeting ACSM PA guidelines. Discussion: There were significant differences between NHB and NHW individuals with arthritis in meeting PA guidelines. After controlling for age, gender, education, and BMI non-Hispanic White individuals were still significantly more likely to meet PA guidelines. Interventions aimed at promoting higher levels of physical activity among individuals with arthritis need to consider neighborhood aesthetics and crime when designing programs. More arthritis-specific programs are needed in close proximity to neighborhoods in an effort to promote physical activity.
ContributorsChuran, Christopher (Author) / Der Ananian, Cheryl (Thesis advisor) / Adams, Marc (Committee member) / Campbell, Kathryn (Committee member) / Arizona State University (Publisher)
Created2013
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
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
Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method proposed to screen and detect lung cancer, eliminating the risks associated with LDCT scans. Known and blinded primary blood sera from participants with lung cancer and no cancer were run on peptide microarrays and analyzed. Immunosignatures for each known sample collectively indicated 120 peptides unique to lung cancer and non-cancer participants. These 120 peptides were used to determine the status of the blinded samples. Verification of the results from Vanderbilt is pending.
ContributorsNguyen, Geneva Trieu (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
I travelled and worked in international fisheries policy for 7 months in preparation for this thesis. During this time I completed one internship in Rome, Italy with the Food and Agriculture Organization of the United Nations (UNFAO) and another internship on the island of Pohnpei with the Secretariat of the Western and Central Pacific Fisheries Commission (WCPFC). From these experiences, I selected the subject of this thesis. My thesis analyzes the management system for South Pacific albacore tuna, the source stock for brands like "Chicken of the Sea" and "Starkist". South Pacific albacore tuna pass through international waters and the waters of several Pacific Island countries and territories, necessitating States to cooperate and coordinate to sustain the future viability of the stock. A case study for transboundary natural resource management, I discuss the institutional complexity that arises from managing such a resource. I use common-pool resource (CPR) theory to describe this complexity, which frames natural resource management as a collective-action problem among resource users. I first conceptualize the management system as having multiple institutional scales and multiple levels of organization. Then, employing Ostrom's 8 design principles for successful CPR management, I conduct a multi-institution analysis of the international, regional, and subregional institutions that participate in the management system. Finally, I also conduct a cross-institution analysis by examining the interactions between these institutions. I find that significant space for theoretical development exists in CPR theory for understanding complex management systems for transboundary natural resources. Furthermore, I find that interactions between institutions create linkages that could be retooled to improve the performance of the South Pacific albacore tuna management system.
ContributorsAbolhassani, Angela Maryam (Author) / Abbott, Kenneth (Thesis director) / Schoon, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor) / Department of English (Contributor)
Created2015-05
Description
This paper explores two areas of study: Colony Collapse Disorder and urban apiculture--the practice of keeping bees in urban areas. Additionally, this paper discusses the ways in which Colony Collapse Disorder has encouraged an increase in urban beekeeping, and the possible role of urban apiculture as a means of combatting the negative effects of Colony Collapse Disorder. The symptoms, history, and possible causes of Colony Collapse Disorder are presented, as well as the important role that honey bees play in human agriculture. Following the discussion of Colony Collapse Disorder is a description of my urban beekeeping apprenticeship at Desert Marigold School where I kept bees, researched various hives, attended a beekeeping workshop in Tucson, and eventually built a hive and established a colony with my mentor. This paper includes a guide to beekeeping basics, as well as a guide to starting a hive based upon the lessons learned during my apprenticeship.
ContributorsRomero, Madelyn Rattan (Author) / Schoon, Michael (Thesis director) / Silcox, Holly (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / School of Geographical Sciences and Urban Planning (Contributor)
Created2015-05
Description
With an excessive amount of resources in the United States healthcare system being spent on the treatment of diseases that are largely preventable through lifestyle change, the need for successful physical activity interventions is apparent. Unfortunately an individual's physical activity and health goals are often not supported by the social context of their daily lives. This single-case design study, Walking Intervention through Text messaging for CoHabiting individuals (WalkIT CoHab), looks at the efficacy of a text based adaptive physical activity intervention to promote walking over a three month period and the effects of social support in intervention performance in three pairs of cohabiting pairs of individuals (n=6). Mean step increase from baseline to intervention ranged from 1300 to 3000 steps per day for all individuals, an average 45.87% increase in physical activity. Goal attainment during the intervention ranged from 43.96% to 71.43%, meaning all participants exceeded the 40% success rate predicted by 60th percentile goals. Social support scores for study partners, unlike social support scores for family and friends, were often in the high social support range and had a moderate increase from pre to post visits for most participants. Although there was variation amongst participants, there was a high correlation in physical activity trends and successful goal attainment in each pair of participants. Less ambitious percentile goals and more personalized motivational text messages might be beneficial to some participants. An extended intervention, something the majority of participants expressed interest in, would further support the efficacy of this behavioral intervention and allow for possible long term benefits of social support in the intervention to be investigated.
ContributorsFernandez, Jacqueline Alyssa (Author) / Adams, Marc (Thesis director) / Angadi, Siddhartha (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
South Mountain is the largest municipal park in the nation. It is a bundled amenity, providing a series of linked services to the surrounding communities. A dataset of 19,209 homes in 155 neighborhoods within three miles of the park was utilized in order to complete a hedonic estimation for two nearby urban villages, Ahwatukee Foothills and South Mountain Village. Measures of access include proximity to the park, trailhead access, and adjacency to the park. Two regressions were estimated, the first including lot characteristics and subdivision fixed effects and the second using the coefficients for each subdivision as the dependent variable. These estimates describe how the location of a house in a subdivision contributes to its conditional mean price. As a result they offer a direct basis for capturing amenities measured at the neighborhood scale on home values. Park proximity, trailhead access and adjacency were found to significantly influence the price of homes at the 5% confidence level in Ahwatukee, but not in South Mountain Village. The results of this study can be applied to issues of environmental justice and park access in determining which areas and attributes of the park are associated with a high premium. Though South Mountain was preserved some time ago, development and future preservation in the City of Phoenix can be informed by such studies.
ContributorsRamakrishna, Saritha Kambhampati (Author) / Abbott, Joshua (Thesis director) / Smith, V. Kerry (Committee member) / Schoon, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Economics Program in CLAS (Contributor) / Department of English (Contributor)
Created2015-05