Matching Items (332)
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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

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
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Description
Bacteria are often regarded s pathogens, with deleterious impacts on the human body. However, it is known that the presence of trillions of bacteria on and in the human body impart beneficial effects on human health. Like a fingerprint, each individual’s microbiome is unique. The composition of bacteria in one

Bacteria are often regarded s pathogens, with deleterious impacts on the human body. However, it is known that the presence of trillions of bacteria on and in the human body impart beneficial effects on human health. Like a fingerprint, each individual’s microbiome is unique. The composition of bacteria in one person’s gut is different from the gut bacteria in another individual. Together, the human gut microbiome is a complex mix of organisms that is commonly referred to as “the second brain.� Its role in the human body goes beyond digestion and immune system function. The health of the microbiome factors into risk for illnesses as diverse as depression, obesity, bowel disorders and autism (Perlmutter et al., 2015). In context of the myriad of bacteria that live on and within the human body, the composition of bacteria in the gut may have the most significant impact on an individual’s well-being. This “superorganism� co-evolved with its host in order to provide essential and mutually beneficial functions (Ragonnaud et al., 2021).

Affecting millions of Americans, depression is one of the leading causes of the Global Burden of Disease (GBD), followed by anxiety (Gibson-Smith et al., 2018). Communication that occurs between the human brain and the gut microbiome has been found to be a major contributor towards mental health. The human gut microbiome is comprised of many microbes that can communicate with the brain through the gut-brain axis. However, factors such as stress and diets can interfere with this process, especially after increasing the permeability of the intestine (Khoshbin et al., 2020). Perturbation of the gut-brain axis has been implicated across a wide scale of neurodegenerative disorders, with respect to psychopathology (Bonaz et al., 2018). The environment of the gut, along with which species reside there, can help determine the link between gut function and disease. Therefore, it may be possible to prevent the degradation of an individual’s immune function and well-being through alteration of the gut microbiome. (abstract)
ContributorsPisarczyk, Nicole (Author) / Penton, Christopher (Thesis director) / Huffman, Holly (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
The Cape Floral Region (CFR) in southwestern South Africa is one of the most diverse in the world, with >9,000 plant species, 70% of which are endemic, in an area of only ~90,000 km2. Many have suggested that the CFR's heterogeneous environment, with respect to landscape gradients, vegetation, rainfall, elevation,

The Cape Floral Region (CFR) in southwestern South Africa is one of the most diverse in the world, with >9,000 plant species, 70% of which are endemic, in an area of only ~90,000 km2. Many have suggested that the CFR's heterogeneous environment, with respect to landscape gradients, vegetation, rainfall, elevation, and soil fertility, is responsible for the origin and maintenance of this biodiversity. While studies have struggled to link species diversity with these features, no study has attempted to associate patterns of gene flow with environmental data to determine how CFR biodiversity evolves on different scales. Here, a molecular population genetic data is presented for a widespread CFR plant, Leucadendron salignum, across 51 locations with 5-kb of chloroplast (cpDNA) and 6-kb of unlinked nuclear (nuDNA) DNA sequences in a dataset of 305 individuals. In the cpDNA dataset, significant genetic structure was found to vary on temporal and spatial scales, separating Western and Eastern Capes - the latter of which appears to be recently derived from the former - with the highest diversity in the heart of the CFR in a central region. A second study applied a statistical model using vegetation and soil composition and found fine-scale genetic divergence is better explained by this landscape resistance model than a geographic distance model. Finally, a third analysis contrasted cpDNA and nuDNA datasets, and revealed very little geographic structure in the latter, suggesting that seed and pollen dispersal can have different evolutionary genetic histories of gene flow on even small CFR scales. These three studies together caution that different genomic markers need to be considered when modeling the geographic and temporal origin of CFR groups. From a greater perspective, the results here are consistent with the hypothesis that landscape heterogeneity is one driving influence in limiting gene flow across the CFR that can lead to species diversity on fine-scales. Nonetheless, while this pattern may be true of the widespread L. salignum, the extension of this approach is now warranted for other CFR species with varying ranges and dispersal mechanisms to determine how universal these patterns of landscape genetic diversity are.
ContributorsTassone, Erica (Author) / Verrelli, Brian C (Thesis advisor) / Dowling, Thomas (Committee member) / Cartwright, Reed (Committee member) / Rosenberg, Michael S. (Committee member) / Wojciechowski, Martin (Committee member) / Arizona State University (Publisher)
Created2013
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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

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
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Description
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great

Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / Arizona State University (Publisher)
Created2012
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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

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
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Description

This thesis looks at how Latinx communities in Wyoming, despite recognizing the impossibility of overcoming the traditional conservative autocracy, still utilize their identity as a political response to unify Latinx communities throughout the state. The project draws from oral histories conducted with Latinx/Chicanx community members in Wyoming, including professors, legislators,

This thesis looks at how Latinx communities in Wyoming, despite recognizing the impossibility of overcoming the traditional conservative autocracy, still utilize their identity as a political response to unify Latinx communities throughout the state. The project draws from oral histories conducted with Latinx/Chicanx community members in Wyoming, including professors, legislators, and everyday citizens.

ContributorsFranco, David (Author) / Fonseca-Chávez, Vanessa (Thesis director) / Martínez, Rafael (Committee member) / College of Integrative Sciences and Arts (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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

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
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Description

Uniforms and logos are an essential part of sports teams and are created with the intention of representing the city and state of their respective teams. More than a uniform: How culture influences the creation of Arizona sports logos and jerseys presents a look at the conversations and processes undergone

Uniforms and logos are an essential part of sports teams and are created with the intention of representing the city and state of their respective teams. More than a uniform: How culture influences the creation of Arizona sports logos and jerseys presents a look at the conversations and processes undergone before teams are able to unveil their new threads. Four local professional teams are involved with this project: Phoenix Suns, Arizona Diamondbacks, Arizona Coyotes and Arizona Cardinals. Members from each of the organizations were interviewed, in addition to Greg Fisher of Fisher Design. Information was gathered from each of those interviews in addition to research done on the history of each of the team’s uniforms. The information was then created into a documentary that consists of visual and verbal components. The film highlights how each team attempts to represent Arizona and its culture when it comes to what they are wearing on the field, court or ice. The interviews capture the mindset of creative teams as they explore growing new ideas and looks, in addition to a historical delve into two of the team’s debuts in the 1990s. Many of Arizona’s sports teams have much more behind their logos and jerseys than meets the eye. The project taught me how adapt broadcast skills into documentary style storytelling and how important visuals are for longer features. The interviews showed that so many things are taken into consideration when designing a sports logo or uniform and the process can take either months or years to finally reach fruition.

ContributorsNoel, Adam Jude (Author) / Dieffenbach, Paola (Thesis director) / Easley, Isaac (Committee member) / College of Integrative Sciences and Arts (Contributor) / Walter Cronkite School of Journalism and Mass Comm (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The COVID-19 pandemic began in March of 2020 and drastically affected the global human population. Millions of people died due to a SARS-CoV-2 infection while many who survived developed devastating sequelae of the disease. In addition, the closure of schools and businesses led to international economic struggle in the year

The COVID-19 pandemic began in March of 2020 and drastically affected the global human population. Millions of people died due to a SARS-CoV-2 infection while many who survived developed devastating sequelae of the disease. In addition, the closure of schools and businesses led to international economic struggle in the year 2020 as global economies declined. Since the beginning of the pandemic, over 200,000 scientific articles have been published and compiled into a database that grows daily— a rare occurrence within the scientific community. This thesis uses natural language processing tools via Python and VOSviewer software to perform a bibliometric analysis on 205,712 papers published between January of 2020 and February of 2021 pertaining to COVID-19. We first investigate how to analyze these publications most effectively in terms of title versus abstract keyword searches, we further obtain the focus of the current scientific literature via co-occurrence analysis and clustering, and we at last discuss the time evolution of these topics over the course of 14 months.

ContributorsLovell, Madison Ray (Author) / Zheng, Wenwei (Thesis director) / Melkozernov, Alexander (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05