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
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
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
Hiking and Hegemony: Destabilizing the nature/culture and gender binaries through outdoor recreation
Description
This paper explores the contested relationships between nature, culture, and gender. In order to analyze these relationships, we look specifically at outdoor recreation. Furthermore, we employ poststructuralist feminist theory in order to produce three frameworks; the first of which is titled Mother Nature’s Promiscuous Past. Rooted in Old World and colonial values, this framework illustrates the flawed feminization of nature by masculinity, and its subsequent extortion of anything related to femininity — including women and nature itself. This belief barred women from nature, resulting in a lack of access for women to outdoor recreation.
Our second framework, titled The Pleasurable Potential of Outdoor Recreation, cites second-wave feminism as a catalyst for women’s participation in wilderness exploration and outdoor recreation. The work of radical feminists and the women’s liberation movement in 1960s and 1970s empowered women at home, in the workplace, and eventually, in the outdoors; women reclaimed their wilderness, yet they continued to employ Framework One’s feminization of nature. Ecofeminsim brought together nature and women, seeking to bring justice to two groups wronged by the same entity: masculinity. In this context, outdoor recreation is empowering for women.
Despite the potential of Framework Two to reinscribe and better the experiences of women in outdoor recreation, we argue that both Frameworks One and Two perpetuate the gender binary and the nature/culture binary, because they are based upon the notion that women are in fact fundamentally different and separate from men, the notion that nature is an entity separate from culture, or human society, as well as the notion that nature is in fact a feminine entity.
Our third framework, Deer Pay No Mind to Your Genitals, engages poststructuralism, asserting that outdoor recreation and activities that occur in nature can serve to destabilize and deconstruct notions of the gender binary. However, we argue that care must be exercised during this process as not to perpetuate the problematic nature/culture binary, a phenomenon that is unproductive in terms of both sustainability and gender liberation. Outdoor recreation has been used by many as a tool to deconstruct numerous societal constraints, including the gender binary; this, however, continues to attribute escapist and isolationist qualities toward nature, and therefore perpetuating the nature/culture divide. Ultimately, we argue outdoor recreation can and should be used as a tool deconstruct the gender binary, however needs to account for the fact that if nature is helping to construct elements of culture, then the two cannot be separate.
Our second framework, titled The Pleasurable Potential of Outdoor Recreation, cites second-wave feminism as a catalyst for women’s participation in wilderness exploration and outdoor recreation. The work of radical feminists and the women’s liberation movement in 1960s and 1970s empowered women at home, in the workplace, and eventually, in the outdoors; women reclaimed their wilderness, yet they continued to employ Framework One’s feminization of nature. Ecofeminsim brought together nature and women, seeking to bring justice to two groups wronged by the same entity: masculinity. In this context, outdoor recreation is empowering for women.
Despite the potential of Framework Two to reinscribe and better the experiences of women in outdoor recreation, we argue that both Frameworks One and Two perpetuate the gender binary and the nature/culture binary, because they are based upon the notion that women are in fact fundamentally different and separate from men, the notion that nature is an entity separate from culture, or human society, as well as the notion that nature is in fact a feminine entity.
Our third framework, Deer Pay No Mind to Your Genitals, engages poststructuralism, asserting that outdoor recreation and activities that occur in nature can serve to destabilize and deconstruct notions of the gender binary. However, we argue that care must be exercised during this process as not to perpetuate the problematic nature/culture binary, a phenomenon that is unproductive in terms of both sustainability and gender liberation. Outdoor recreation has been used by many as a tool to deconstruct numerous societal constraints, including the gender binary; this, however, continues to attribute escapist and isolationist qualities toward nature, and therefore perpetuating the nature/culture divide. Ultimately, we argue outdoor recreation can and should be used as a tool deconstruct the gender binary, however needs to account for the fact that if nature is helping to construct elements of culture, then the two cannot be separate.
ContributorsPolick-Kirkpatrick, Kaelyn (Co-author) / Downing, Haley Marie (Co-author) / Dove-Viebahn, Aviva (Thesis director) / Schoon, Michael (Committee member) / School of Sustainability (Contributor) / School of Social Transformation (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12