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Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7 in regulating polarization and inflammatory responses in bone marrow derived

Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7 in regulating polarization and inflammatory responses in bone marrow derived macrophages. In primary bone marrow derived macrophages, LPS induced significant pro-inflammatory responses. LysM-Cre induced SIRT7 knockout (KO) male macrophages exhibited enhanced inflammatory responses compared to WT macrophages. Interestingly, we did not observe a similar trend in female cells. In fact, loss of SIRT7 in female macrophages induced weaker proinflammatory responses when challenged with LPS. As an epigenetic co-factor, SIRT7 is known to interact with multiple inflammation related nuclear hormone receptors, such as glucocorticoid receptor (GR), and vitamin D receptor (VDR). Therefore, we examined whether the glucocorticoid or vitamin D induced anti-inflammatory responses are affected in SIRT7 KO macrophages. Preliminary results suggest that both glucocorticoid and vitamin D are still able to inhibit LPS-induced inflammatory responses in SIRT7 KO cells. Future studies using RNA-seq and epigenetic assays will be needed to determine the sex-specific function of SIRT7 in macrophage activation. 
ContributorsMikkilineni, Sneha (Author) / Katsanos, Christos (Thesis director) / Wei, Zong (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description
Mutation rate is the rate of appearance for mutations to occur in a living organism. Studying and quantifying mutation rates and their evolution is important because mutations are the ultimate source of genetic variation and one of the reasons why evolution occurs. Much of the current research has investigated the

Mutation rate is the rate of appearance for mutations to occur in a living organism. Studying and quantifying mutation rates and their evolution is important because mutations are the ultimate source of genetic variation and one of the reasons why evolution occurs. Much of the current research has investigated the mutational rate increase. The evolution of reduced mutation rate, which can be favored by natural selection because the accumulation of too many mutations can be deleterious and result in death, is less studied. Therefore, this study will be focused on antimutators, which are mutations that result in a lowering of the mutation rate. Using Escherichia coli K-12 str. MG1655 as a model system, the effects and reasons for how MMR- background E. coli evolves lower mutation rates were studied. Here we show that the candidate antimutator in dnaE lowers the mutation rate in an experimentally evolved population of E. coli with MMR- background by using a mutation rate assay to demonstrate the difference between populations with and without the antimutator candidate. The results also suggest the importance of an antimutator for populational survival.
ContributorsGraham, Logan (Author) / Ho, Wei-Chin (Thesis director) / Lynch, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description
Mycobacterium abscessus (Mabs) is a multidrug-resistant nontuberculous mycobacterium capable of causing persistent pulmonary infection. It most prominently threatens those with cystic fibrosis (CF), a progressive and genetic disorder characterized by an immunocompromised respiratory tract. Current treatments fail to eradicate Mabs, meaning novel alternatives are greatly needed. Antimicrobial peptides (AMPs) are

Mycobacterium abscessus (Mabs) is a multidrug-resistant nontuberculous mycobacterium capable of causing persistent pulmonary infection. It most prominently threatens those with cystic fibrosis (CF), a progressive and genetic disorder characterized by an immunocompromised respiratory tract. Current treatments fail to eradicate Mabs, meaning novel alternatives are greatly needed. Antimicrobial peptides (AMPs) are short sequences of amino acids that display broad-spectrum antimicrobial activity and play an important role in innate immunity. To maximize their therapeutic potential, key AMP features can be rationally combined through an iterative engineering process to create synthetic, designed AMPs (dAMPs). In this investigation, two dAMPs, RP554 and RP557, reduced Mabs ATCC 19977 viability by 99.99% and were subjected to further testing. In antimicrobial susceptibility testing with Mabs ATCC 19977, RP554 and RP557 demonstrated bactericidal activity at concentrations 16-32 μM. Complete killing of Mabs ATCC 19977 by RP554 and RP557 occurred rapidly in <24 h. RP554 and RP557 also inhibited 20 Mabs clinical isolates obtained from CF patients. Furthermore, RP554 and RP557 retained anti-Mabs activity after pre-exposure to human serum, indicating potential stability in blood. Conversely, the tested dAMPs did not kill Mabs during in vitro experiments in an artificial sputum medium. Novel antimicrobials, such as the RP554 and RP557 dAMPs, offer therapeutic potential for otherwise resistant bacterial pathogens, including Mabs, that afflict both CF and non-CF patients.
ContributorsBrandt, McKenzie (Author) / Haydel, Shelley (Thesis director) / Bean, Heather (Committee member) / Dermody, Roslyn (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description
Biological therapies are substances made from living organisms used to treat disease or injury. Common biologic therapies today include platelet rich plasma injections (PRP), stem cell therapy, and growth factor therapy. Ever since their emergence just over a decade ago, biological treatments have been used to treat a variety of

Biological therapies are substances made from living organisms used to treat disease or injury. Common biologic therapies today include platelet rich plasma injections (PRP), stem cell therapy, and growth factor therapy. Ever since their emergence just over a decade ago, biological treatments have been used to treat a variety of conditions including tendonitis. Tendonitis commonly affects athletes of all levels and is the inflammation or irritation of a tendon that leads to pain and tenderness. Despite the potential promise of biological treatments in treating persistent injuries like tendonitis, there is not a consensus in the scientific community on their effectiveness in treating non-surgical injuries. However, many athletes still seek these forms of treatment. Currently, there are many unknowns regarding how up and coming high-level athletes perceive biologics, if they understand what biologics are, how they’re learning about biologics, and what type of injuries they believe should warrant biologics treatment. Here we show that the majority of high-level collegiate athletes at Arizona State University (ASU) know what biological therapies are, but do not possess accurate information about their effectiveness and medical use. We found through a survey sent out to the student athletes at ASU that while athletes are familiar with PRP and stem cell injections, they are primarily learning about them from potentially unreliable sources such as social media, friends, and family. Further, student athletes falsely perceive biologics are commonly used in physician treatment protocols for persistent tendonitis and are recommended to athletes months earlier than in reality. Our results demonstrate that high-level collegiate athletes do have a misperception on the effectiveness of biological treatments and that further education is needed for athletes about the truth and myths of biologics.
ContributorsSmith, Haley (Author) / Holloway, Julianne (Thesis director) / Chhabra, Anikar (Committee member) / Brinkman, Joseph (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description

The Riparian Preserve at Gilbert Water Ranch (“the Riparian”) is an urban park and water recharge facility in Gilbert, Arizona. Through interviewing several individuals involved in the process of conceptualizing. creating, and maintaining the Riparian and researching its past and present, this paper seeks to understand how the urban park

The Riparian Preserve at Gilbert Water Ranch (“the Riparian”) is an urban park and water recharge facility in Gilbert, Arizona. Through interviewing several individuals involved in the process of conceptualizing. creating, and maintaining the Riparian and researching its past and present, this paper seeks to understand how the urban park came to be and how it appears today. This includes a history of groundwater management and recharge in Arizona, the voices of people who have worked on the Riparian, the current state of the preserve, and maintenance challenges to inform readers the importance of such areas and promote the creation of similar multi-faceted recharge areas. Freedom of information act requests, academic literature, town minutes, media accounts, and information from the Town of Gilbert website place the interviews into context and illustrate the multi-use nature of the park. Furthermore, through descriptions of the history, design, stakeholders, conservation and educational value, this paper seeks to demonstrate the full picture of the urban park from past to present. The Riparian Preserve and its history illustrate the importance of gazing into the future of water conservation, and how doing so could create an amenity to be enjoyed for generations to come.

ContributorsMiller, Taylor (Author, Co-author) / Chew, Matthew (Thesis director) / Minteer, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor)
Created2022-05
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Description
Upon analyzing the literature that is available on refugee populations in conjunction with our personal experiences with these populations, we ultimately decided to develop a mobile app that targeted the source of the numerous disparities we saw. These disparities ranged from increased prevalence of chronic diseases to difficulty in going

Upon analyzing the literature that is available on refugee populations in conjunction with our personal experiences with these populations, we ultimately decided to develop a mobile app that targeted the source of the numerous disparities we saw. These disparities ranged from increased prevalence of chronic diseases to difficulty in going to doctor's appointments due to transportation challenges. We focused on the three areas of government assistance, clinical health, and general well-being through our mobile app, Refugee Aid Initiative. This mobile app is designed to provide refugee populations with the resources necessary to build healthier, happier, and more independent lives for themselves and their families. Here, we focus on not only highlighting resources that are available but also adding supplementary information that helps refugee populations fully take advantage of the resources that are available to them.
ContributorsElsabbagh, Zaid (Author) / Bcharah, George (Co-author) / Sellner, Erin (Thesis director) / Jakubczak, Laura (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description

Cells have mechanisms in place to maintain the specific lipid composition of distinct organelles including vesicular transport by the endomembrane system and non-vesicular lipid transport by lipid transport proteins. Oxysterol Binding Proteins (OSBPs) are a family of lipid transport proteins that transfer lipids at various membrane contact sites (MCSs). OSBPs

Cells have mechanisms in place to maintain the specific lipid composition of distinct organelles including vesicular transport by the endomembrane system and non-vesicular lipid transport by lipid transport proteins. Oxysterol Binding Proteins (OSBPs) are a family of lipid transport proteins that transfer lipids at various membrane contact sites (MCSs). OSBPs have been extensively investigated in human and yeast cells where twelve have been identified in Homo sapiens and seven in Saccharomyces cerevisiae. The evolutionary relationship between these well-characterized OSBPs is still unclear. Reconstructed OSBP phylogenies revealed that the ancestral Saccharomycotinan had four OSBPs, the ancestral Holomycotan had five OSBPs, the ancestral Holozoan had six OSBPs, the ancestral Opisthokont had three OSBPs, and the ancestral Eukaroyte had three OSBPs. Our analysis identified three clades of ancient OSBPs not present in animals or fungi.

ContributorsSingh, Rohan (Author) / Wideman, Jeremy (Thesis director) / Gile, Gillian (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor)
Created2022-05