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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 study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of this study is to first investigate the role of political socialization on young men and women and what motivates them to become politically active and make the ultimate decision to run for elected office. These effects include parental attitudes, exposure to political shows and news sources, participation in voluntary organizations, and overall community involvement. After understanding these direct and indirect effects of political socialization, I can attempt to explain the causes for the gender gap in political ambition \u2014 meaning that significantly more men are running for elected office compared to women.
ContributorsOsgood, Shannon Marie (Author) / Woodall, Gina (Thesis director) / Herrera, Richard (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Public Affairs (Contributor) / School of Politics and Global Studies (Contributor)
Created2015-05
Description
The Undoing Project is an ongoing educational feminist YouTube channel that serves as an introduction to feminism and feminist theory. The objective for this project is to present feminist theory and feminist ideology in an accessible and entertaining way. Through this project I sought to accomplish three goals: to challenge the negative image of feminism, bridge the gap between the language of academia and the public, and to acknowledge and unlearn ingrained prejudices. The videos focus on theory, history, legislation, current events, and pop culture. The initial project consists of ten videos addressing the feminist wave models, a brief history of the feminist movement, and discussions of concepts like hegemony, intersectionality, masculinity, femininity, and race.
ContributorsBuchholtz, Kaylee Marie (Author) / Brian, Jennifer (Thesis director) / Grzanka, Patrick (Committee member) / Brouwer, Dan (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor)
Created2015-05
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Previous research has found improvements in motor and cognitive measures following Assisted Cycle Therapy (AC) in adolescence with Down syndrome (DS). Our study investigated whether we would find improvements in older adults with DS on measures of leisure physical activity (GLTEQ) and sleep, which are early indicators of Alzheimer's disease (AD) in persons with Down syndrome. This study consisted of eight participants with Down syndrome between 31 and 51 years old that cycled for 30 minutes 3 x/week for eight weeks either at their voluntary cycling rate (VC) or approximately 35% faster with the help of a mechanical motor (AC). We predicted that, based on pilot data (Gomez, 2015), GLTEQ would either maintain or improve after AC, but would decrease after VC and would stay the same after NC. We predicted that the sleep score may improve after both VC or AC or it may improve more after VC than AC based on pilot data related to leisure activity. Our results were consistent with our prediction that GLTEQ will either maintain or improve after AC but will decrease after VC. Our results were not consistent with our prediction that sleep may improve after both VC or AC or it may improve more after VC than AC, possibly because we did not pre-screen for sleep disorders. Future research should focus on recruiting more participants and using both objective and subjective measures of sleep and physical activity to improve the efficacy of the study.
ContributorsParker, Lucas Maury (Author) / Ringenbach, Shannon (Thesis director) / Buman, Matthew (Committee member) / Holzapfel, Simon (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Nutrition and Health Promotion (Contributor) / College of Public Service and Community Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Surrounded by a developmental boom in downtown Phoenix, Roosevelt Row fights to maintain the local art influence and historic character. An earthy community of street artists, coffee drinkers, band tees, nose rings, vinyl collectors and rolled denim, the people are facing dramatic urbanization. The hum of drills, hammers, cranes and alarms sound throughout the viscidity, echoing the construction of a new era downtown. In the interest of better understanding the developmental process, resident needs and community, this research project evaluates successful public spaces and similar downtown areas in the United States, synthesized their elements of prosperity in comparison to general attributes of quality public spaces, and implemented the concepts and ideas into Roosevelt Row. This provided the researcher with knowledge of quality public spaces, why public space is important, and how placemaking is routinely accomplished. This also equipped the researcher with the tools to participate in ethnography and collect observational data to learn about Roosevelt Row. The researcher then combined learned material with what she observed on the Row, to condense the artists' district developmental needs into nine proposals for bettering the Row in the immediate, near and long-term future. The study begs to answer the question: is Roosevelt Row a Place or a place? Observation, residential and visitor engagement with the space; locality, pleasurability, inclusiveness and safety of the public spaces; and relationship between residents and quality of space all contribute to the space's qualifications. While Roosevelt Row has the potential and assets to become a Place, especially if the nine proposals are implemented. However, at the time of research, the space is between place and Place.
ContributorsStobbe, Brooke Elizabeth (Author) / Larsen, Dale (Thesis director) / Knopf, Richard (Committee member) / College of Public Service and Community Solutions (Contributor) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Background
Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas.
Methods
Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention.
Results
The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance.
Conclusions
Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat.
Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas.
Methods
Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention.
Results
The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance.
Conclusions
Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat.
ContributorsKeller, Colleen (Author) / Ainsworth, Barbara (Author) / Records, Kathryn (Author) / Todd, Michael (Author) / Belyea, Michael (Author) / Vega Lopez, Sonia (Author) / Permana, Paska (Author) / Coonrod, Dean (Author) / Williams, Allison (Author) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor) / College of Public Service and Community Solutions (Contributor) / Southwest Interdisciplinary Research Center (Contributor)
Created2014-09-19
Description
In the face of rising rates of substance use among Mexican youth and rapidly narrowing gender differences in use, substance use prevention is an increasingly urgent priority for Mexico. Prevention interventions have been implemented in Mexico but few have been rigorously evaluated for effectiveness. This article presents the long term effects of a Mexico-based pilot study to test the feasibility of a linguistically specific (Mexican Spanish) adapted version of keepin’ it REAL, a school-based substance abuse prevention model program. University affiliated researchers from Mexico and the US collaborated on the study design, program implementation, data collection, and analysis. Students and their teachers from two middle schools (secundarias) in Guadalajara participated in this field trial of Mantente REAL (translated to Spanish). The schools were randomly assigned to treatment and control conditions. The sample of 431 students reported last 30 day substance use at three times (one pretest and two posttests). Changes in substance use behaviors over time were examined using growth curve models. Long term desired intervention effects were found for alcohol and marijuana use but not for cigarettes. The intervention effects were greater for girls than for boys in slowing the typical developmental increase over time in alcohol use. Marijuana effects were based on small numbers of users and indicate a need for larger scale studies. These findings suggest that keepin’ it REAL is a promising foundation for cultural program adaptation efforts to create efficacious school-based universal prevention interventions for middle school students in Mexico.
ContributorsMarsiglia, Flavio (Author) / Kulis, Stephen (Author) / Booth, Jaime (Author) / Nuno-Gutierrez, Bertha L. (Author) / Robbins, Danielle (Author) / College of Public Service and Community Solutions (Contributor) / School of Social Work (Contributor) / College of Liberal Arts and Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Southwest Interdisciplinary Research Center (Contributor)
Created2015-04-01