ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Rhodoferax antarcticus strain ANT.BR, a purple nonsulfur bacterium isolated from a microbial mat in Ross Island, Antarctica, is the first described anoxygenic phototrophic bacterium that is adapted to cold habitats and is the first beta-proteobacterium to undergo complete genome sequencing. R. antarcticus has unique absorption spectra and there are no obvious intracytoplasmic membranes in cells grown phototrophically, even under low light intensity. Analysis of the finished genome sequence reveals a single chromosome (3,809,266 bp) and a large plasmid (198,615 bp) that together harbor 4,262 putative genes. The genome contains two types of Rubiscos, Form IAq and Form II, which are known to exhibit quite different kinetic properties in other bacteria. The presence of multiple Rubisco forms could give R. antarcticus high metabolic flexibility in diverse environments. Annotation of the complete genome sequence along with previous experimental results predict the presence of structural genes for three types of light-harvesting (LH) complexes, LH I (B875), LH II (B800/850), and LH III (B800/820). There is evidence that expression of genes for the LH II complex might be inhibited when R. antarcticus is under low temperature and/or low light intensity. These interesting condition-dependent light-harvesting apparatuses and the control of their expression are very valuable for the further understanding of photosynthesis in cold environments. Finally, R. antarcticus exhibits a highly motile lifestyle. The genome content and organization of all putative polar flagella genes are characterized and discussed.
ContributorsZhao, Tingting, M.S (Author) / Touchman, Jeffrey (Thesis advisor) / Rosenberg, Michael (Committee member) / Redding, Kevin (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
Guided by Tinto’s Theory of College Student Departure, I conducted a set of five studies to identify factors that influence students’ social integration in college science active learning classes. These studies were conducted in large-enrollment college science courses and some were specifically conducted in undergraduate active learning biology courses. Using qualitative and quantitative methodologies, I identified how students’ identities, such as their gender and LGBTQIA identity, and students’ perceptions of their own intelligence influence their experience in active learning science classes and consequently their social integration in college. I also determined factors of active learning classrooms and instructor behaviors that can affect whether students experience positive or negative social integration in the context of active learning. I found that students’ hidden identities, such as the LGBTQIA identity, are more relevant in active learning classes where students work together and that the increased relevance of one’s identity can have a positive and negative impact on their social integration. I also found that students’ identities can predict their academic self-concept, or their perception of their intelligence as it compares to others’ intelligence in biology, which in turn predicts their participation in small group-discussion. While many students express a fear of negative evaluation, or dread being evaluated negatively by others when speaking out in active learning classes, I identified that how instructors structure group work can cause students to feel more or less integrated into the college science classroom. Lastly, I identified tools that instructors can use, such as name tents and humor, which can positive affect students’ social integration into the college science classroom. In sum, I highlight inequities in students’ experiences in active learning science classrooms and the mechanisms that underlie some of these inequities. I hope this work can be used to create more inclusive undergraduate active learning science courses.
ContributorsCooper, Katelyn M (Author) / Brownell, Sara E (Thesis advisor) / Stout, Valerie (Committee member) / Collins, James (Committee member) / Orchinik, Miles (Committee member) / Zheng, Yi (Committee member) / Arizona State University (Publisher)
Created2018
Description
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative enteric pathogen that causes self-limiting gastroenteritis in healthy individuals and can cause systemic infections in those who are immunocompromised. During its natural lifecycle, S. Typhimurium encounters a wide variety of stresses it must sense and respond to in a dynamic and coordinated fashion to induce resistance and ensure survival. Salmonella is subjected to a series of stresses that include temperature shifts, pH variability, detergent-like bile salts, oxidative environments and changes in fluid shear levels. Previously, our lab showed that cultures of S. Typhimurium grown under physiological low fluid shear (LFS) conditions similar to those encountered in the intestinal tract during infection uniquely regulates the virulence, gene expression and pathogenesis-related stress responses of this pathogen during log phase. Interestingly, the log phase Salmonella mechanosensitive responses to LFS were independent of the master stress response sigma factor, RpoS, departing from our conventional understanding of RpoS regulation. Since RpoS is a growth phase dependent regulator with increased stability in stationary phase, the current study investigated the role of RpoS in mediating pathogenesis-related stress responses in stationary phase S. Typhimurium grown under LFS and control conditions. Specifically, stationary phase responses to acid, thermal, bile and oxidative stress were assayed. To our knowledge the results from the current study demonstrate the first report that the mechanical force of LFS globally alters the S. Typhimurium χ3339 stationary phase stress response independently of RpoS to acid and bile stressors but dependently on RpoS to oxidative and thermal stress. This indicates that fluid shear-dependent differences in acid and bile stress responses are regulated by alternative pathway(s) in S. Typhimurium, were the oxidative and thermal stress responses are regulated through RpoS in LFS conditions. Results from this study further highlight how bacterial mechanosensation may be important in promoting niche recognition and adaptation in the mammalian host during infection, and may lead to characterization of previously unidentified pathogenesis strategies.
ContributorsCrenshaw, Keith (Author) / Nickerson, Cheryl A. (Thesis advisor) / Barrila, Jennifer (Thesis advisor) / Ott, C. (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2016
Description
Emergence of multidrug resistant (MDR) bacteria is a major concern to global health. One of the major MDR mechanisms bacteria employ is efflux pumps for the expulsion of drugs from the cell. In Escherichia coli, AcrAB-TolC proteins constitute the major chromosomally-encoded drug efflux system. AcrB, a trimeric membrane protein is well-known for its substrate promiscuity. It has the ability to efflux a broad spectrum of substrates alongside compounds such as dyes, detergent, bile salts and metabolites. Newly identified AcrB residues were shown to be functionally relevant in the drug binding and translocation pathway using a positive genetic selection strategy. These residues—Y49, V127, D153, G288, F453, and L486—were identified as the sites of suppressors of an alteration, F610A, that confers a drug hypersensitivity phenotype. Using site-directed mutagenesis (SDM) along with the real-time efflux and the classical minimum inhibitory concentration (MIC) assays, I was able to characterize the mechanism of suppression.
Three approaches were used for the characterization of these suppressors. The first approach focused on side chain specificity. The results showed that certain suppressor sites prefer a particular side chain property, such as size, to overcome the F610A defect. The second approach focused on the effects of efflux pump inhibitors. The results showed that though the suppressor residues were able to overcome the intrinsic defect of F610A, they were unable to overcome the extrinsic defect caused by the efflux pump inhibitors. This showed that the mechanism by which F610A imposes its effect on AcrB function is different than that of the efflux pump inhibitors. The final approach was to determine whether suppressors mapping in the periplasmic and trans-membrane domains act by the same or different mechanisms. The results showed both overlapping and distinct mechanisms of suppression.
To conclude, these approaches have provided a deeper understanding of the mechanisms by which novel suppressor residues of AcrB overcome the functional defect of the drug binding domain alteration, F610A.
Three approaches were used for the characterization of these suppressors. The first approach focused on side chain specificity. The results showed that certain suppressor sites prefer a particular side chain property, such as size, to overcome the F610A defect. The second approach focused on the effects of efflux pump inhibitors. The results showed that though the suppressor residues were able to overcome the intrinsic defect of F610A, they were unable to overcome the extrinsic defect caused by the efflux pump inhibitors. This showed that the mechanism by which F610A imposes its effect on AcrB function is different than that of the efflux pump inhibitors. The final approach was to determine whether suppressors mapping in the periplasmic and trans-membrane domains act by the same or different mechanisms. The results showed both overlapping and distinct mechanisms of suppression.
To conclude, these approaches have provided a deeper understanding of the mechanisms by which novel suppressor residues of AcrB overcome the functional defect of the drug binding domain alteration, F610A.
ContributorsBlake, Mellecha (Author) / Misra, Rajeev (Thesis advisor) / Stout, Valerie (Committee member) / Wang, Xuan (Committee member) / Arizona State University (Publisher)
Created2016
Description
A dental exam in twenty-first century America generally includes the taking of radiographs, which are x-ray images of the mouth. These images allow dentists to see structures below the gum line and within the teeth. Having a patient's radiographs on file has become a dental standard of care in many states, but x-rays were only discovered a little over 100 years ago. This research analyzes how and why the x-ray image has become a ubiquitous tool in the dental field. Primary literature written by dentists and scientists of the time shows that the x-ray was established in dentistry by the 1950s. Therefore, this thesis tracks the changes in x-ray technological developments, the spread of information and related safety concerns between 1890 and 1955. X-ray technology went from being an accidental discovery to a device commonly purchased by dentists. X-ray information started out in the form of the anecdotes of individuals and led to the formation of large professional groups. Safety concerns of only a few people later became an important facet of new devices. These three major shifts are described by looking at those who prompted the changes; they fall into the categories of people, technological artifacts and institutions. The x-ray became integrated into dentistry as a product of the work of people such as C. Edmund Kells, a proponent of dental x-rays, technological improvements including faster film speed, and the influence of institutions such as Victor X-Ray Company and the American Dental Association. These changes that resulted established a strong foundation of x-ray technology in dentistry. From there, the dental x-ray developed to its modern form.
ContributorsMartinez, Britta (Author) / Ellison, Karin (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2013
Description
In the US, menstrual education, which provides key information about menstrual hygiene and health to both young girls and boys, historically lacks biologically accurate information about the menstrual cycle and perpetuates harmful perceptions about female reproductive health. When people are unable to differentiate between normal and abnormal menstrual bleeding, based on a lack of quality menstrual education, common gynecological conditions often remain underreported. This raises a question as to how girls’ menstrual education experiences influence the ways in which they perceive normal menstrual bleeding and seek treatment for common abnormalities, such as heavy, painful, or irregular menstrual bleeding. A mixed methods approach allowed evaluation of girls’ abilities to recognize abnormal menstrual bleeding. A literature review established relevant historical and social context on the prevalence and quality of menstrual education in the US. Then, five focus groups, each including five to eight college-aged women, totaling thirty-three participants, allowed for macro-level analysis of current challenges and gaps in knowledge related to menstruation. To better examine the relationship between menstrual education and reproductive health outcomes, twelve semi-structured, one-on-one interviews allowed micro-level analysis. Those interviews consisted of women diagnosed with endometriosis and polycystic ovary syndrome, common gynecological conditions that include abnormal menstrual bleeding. Developing a codebook of definitions and exemplars of significant text segments and applying it to the collected data revealed several themes. For example, mothers, friends, teachers, the Internet, and social media are among the most common sources of information about menstrual hygiene and health. Yet, women reported that those sources of information often echoed stigmatized ideas about menstruation, eliciting feelings of shame and fear. That poor quality of information was instrumental to women’s abilities to detect and report abnormal menstrual bleeding. Women desire and need biologically accurate information about reproductive health, including menstruation and ovulation, fertility, and methods of birth control as treatments for abnormal menstrual bleeding. Unfortunately, menstrual education often leaves girls ill-equipped to identify and seek treatment for common gynecological conditions. Those findings may influence current menstrual education, incorporating biological information and actively dismissing common misconceptions about menstruation that influence stigma.
ContributorsSantora, Emily Katherine (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Committee member) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2021
Description
Innovations in undergraduate education have increased the prevalence of active learning courses, online education, and student engagement in the high-impact practice of undergraduate research, however it is unknown whether students with disabilities are able to engage in these innovative learning environments to the same extent that they are able to engage in more traditional learning environments. Universities, disability resource centers, and instructors are mandated to provide accommodations to students with disabilities for the purposes of prohibiting discrimination and ensuring equal access to opportunities for individuals with disabilities. Are accommodations being adapted and created for these new types of learning environments? This dissertation reports findings from four studies about the experiences of students with disabilities in these three learning environments, specifically examining the challenges students with disabilities encounter and the emerging recommendations for more effective accommodations. I find that students with disabilities experience challenges in each of these learning environments and that the current suite of accommodations are not sufficient for students with disabilities. I argue that institutions need to consider modifying student accommodations and the process for obtaining them to better support students with disabilities in these evolving learning environments. I also provide recommendations for the ways in which undergraduate science education can be made more accessible and inclusive of students with disabilities.
ContributorsGin, Logan Eugene (Author) / Brownell, Sara E. (Thesis advisor) / Cooper, Katelyn M. (Thesis advisor) / Collins, James P. (Committee member) / Stout, Valerie (Committee member) / Zheng, Yi (Committee member) / Arizona State University (Publisher)
Created2021