Matching Items (64)
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
Purpose: To examine: (1) whether Non-Hispanic Blacks (NHB) and Non-Hispanic Whites (NHW) with diagnosed arthritis differed in self-reported physical activity (PA) levels, (2) if NHB and NHW with arthritis differed on potential correlates of PA based on the Social Ecological Model (Mcleroy et al., 1988), and (3) if PA participation varied by race/ethnicity after controlling for age, gender, education, and BMI. Methods: This study was a secondary data analysis of data collected from 2006-2008 in Chicago, IL as part of the Midwest Roybal Center for Health Promotion. Bivariate analyses were used to assess potential differences between race in meeting either ACR or ACSM PA guidelines. Comparisons by race between potential socio-demographic correlates and meeting physical activity guidelines were assessed using Chi-squares. Potential differences by race in psychosocial, arthritis, and health-related and environmental correlates were assessed using T-tests. Finally, logistic regression analyses were used to examine if race was still associated with PA after controlling for socio-demographic characteristics. Results: A greater proportion of NHW (68.1% and 35.3%) than NHB (46.5% and 20.9%) met both the arthritis-specific and the American College of Sports Medicine (ACSM) recommendations for physical activity, respectively. NHB had significantly lower self-efficacy for exercise and reported greater impairments in physical function compared to NHW. Likewise, NHB reported more crime and less aesthetics within their neighborhood. NHW were 2.56 times more likely to meet arthritis-specific PA guidelines than NHB after controlling for age, gender, education, marital status, and BMI. In contrast, after controlling for sociodemographic characteristics, age and gender were the only significant predictors of meeting ACSM PA guidelines. Discussion: There were significant differences between NHB and NHW individuals with arthritis in meeting PA guidelines. After controlling for age, gender, education, and BMI non-Hispanic White individuals were still significantly more likely to meet PA guidelines. Interventions aimed at promoting higher levels of physical activity among individuals with arthritis need to consider neighborhood aesthetics and crime when designing programs. More arthritis-specific programs are needed in close proximity to neighborhoods in an effort to promote physical activity.
ContributorsChuran, Christopher (Author) / Der Ananian, Cheryl (Thesis advisor) / Adams, Marc (Committee member) / Campbell, Kathryn (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
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
With an excessive amount of resources in the United States healthcare system being spent on the treatment of diseases that are largely preventable through lifestyle change, the need for successful physical activity interventions is apparent. Unfortunately an individual's physical activity and health goals are often not supported by the social context of their daily lives. This single-case design study, Walking Intervention through Text messaging for CoHabiting individuals (WalkIT CoHab), looks at the efficacy of a text based adaptive physical activity intervention to promote walking over a three month period and the effects of social support in intervention performance in three pairs of cohabiting pairs of individuals (n=6). Mean step increase from baseline to intervention ranged from 1300 to 3000 steps per day for all individuals, an average 45.87% increase in physical activity. Goal attainment during the intervention ranged from 43.96% to 71.43%, meaning all participants exceeded the 40% success rate predicted by 60th percentile goals. Social support scores for study partners, unlike social support scores for family and friends, were often in the high social support range and had a moderate increase from pre to post visits for most participants. Although there was variation amongst participants, there was a high correlation in physical activity trends and successful goal attainment in each pair of participants. Less ambitious percentile goals and more personalized motivational text messages might be beneficial to some participants. An extended intervention, something the majority of participants expressed interest in, would further support the efficacy of this behavioral intervention and allow for possible long term benefits of social support in the intervention to be investigated.
ContributorsFernandez, Jacqueline Alyssa (Author) / Adams, Marc (Thesis director) / Angadi, Siddhartha (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (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
An increasingly sedentary population in the United States, specifically with adolescents, is putting youth at risk of future health related trauma and disease. This single-case design study, Walking Intervention Through Text Messaging for Adolescents (WalkIT-A), was used to intervene with a 12-year old, physically inactive male, in an attempt to test the efficacy of a 12-week physical activity program that may help reduce health risks by increasing number of steps walked per day. The components of the intervention consisted of a FitBit Zip pedometer, physical activity education, text messages, monetary incentives, and goal setting that adapted personally to the participant. Mean step count increased by 30% from baseline (mean = 3603 [sd = 1983]) to intervention (mean = 4693 [sd = 2112]); then increased slightly by 6.7% from intervention to withdrawal (mean = 5009 [sd = 2152]). Mean "very active minutes" increased by 45% from baseline (mean = 8.8 [sd = 8.9]) to intervention (mean = 12.8 [sd = 9.6]); then increased by 61.7% from intervention to withdrawal (mean = 20.7 [sd = 8.4]). Weight, BMI, and blood pressure all increased modestly from pre to post. Cardiovascular fitness (estimated VO2 max) improved by 12.5% from pre (25.5ml*kg-1*min-1) to post (28.7ml*kg-1*min-1). The intervention appeared to have a delayed and residual effect on the participant's daily steps and very active minutes. Although the idealistic ABA pattern did not occur, and the participant did not meet the target of 11,500 daily steps, a positive trend toward that target behavior in the latter 1/3rd of the intervention was observed. Results suggest the need for an extended intervention over a longer period of time and customized even further to the participant.
ContributorsLamb, Nicholas Reid (Author) / Adams, Marc (Thesis director) / Ainsworth, Barbara (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2014-12
Description
The WalkIT Study is a mobile health study examining the efficacy of a four month text message-based intervention for increasing physical activity among 96 overweight adults. The purpose of this thesis is to examine the potency of the different types of motivational prompt-to-action text messages used in the WalkIT Study for increasing steps per day by examining the individual messages, creating qualitative themes and comparing themed groups, and evaluating the interaction between demographic subgroups and themed groups. A total of nine themes was created. The results found that Message 13, “It doesn't matter how old you are – it's never too early or too late to become physically active so start today; only then will you start to see results!”, had the highest median step count (7129 steps) and Message 71, “It's ok if you can't reach your goal today. Just push yourself more tomorrow.”, had the lowest median step count (5054 steps). For themes, the highest median step count (6640 steps) was found in Theme 6, Challenges, and the lowest median step count (5450 steps) was found in Theme 9, Unconditional Feedback. Theme 6 (Challenges) had the highest median step count for females, Theme 7 (Everyday Tips) had the highest median step count for males, Theme 4 (Nutrition) had the highest median step count for the 18-42 group, Theme 6 (Challenges) had the highest median step count for the 43-61 group, and Theme 9 (Unconditional Feedback) had the lowest median step count for both genders and both age groups. The results suggest the usefulness of analyzing the effectiveness of individual motivational text messages, themes, and the interaction between demographic groups and themes in physical activity interventions.
ContributorsBhuiyan, Nishat Anjum (Author) / Adams, Marc (Thesis director) / Ainsworth, Barbara (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
The SARS-CoV-2 (Covid-19) virus has had severe impacts on college students' ways of life. To examine how students were coping and perceiving the Covid-19 pandemic, a secondary analysis of an online survey across the three Arizona public universities investigated students’ knowledge about Covid-19, engagement with preventive strategies, pandemic preparedness and gauged their risk perception. Results from our analysis indicate that the students were knowledgeable about Covid-19 and were changing their habits and engaging with preventive measures. Results further suggest that students were prepared for the pandemic in terms of resources and were exhibiting high-risk perceptions. The data also revealed that students who were being cautious and engaging with preventive behaviors had a higher risk-perception than individuals who were not. As for individuals who were prepared for the pandemic in terms of supplies, their risk perception was similar to those who did not have supplies. Individuals who were prepared and capable of providing a single caretaker to tend to their sick household members and isolate them in a separate room had a higher risk perception than those who could not. These results can help describe how college students will react to a future significant event, what resources students may be in need of, and how universities can take additional steps to keep their students safe and healthy. The results from this study and recommendations will provide for a stronger and more understanding campus community during times of distress and can improve upon already established university protocols for health crises and even natural disasters.
ContributorsNaqvi, Avina Itrat (Co-author) / Shaikh, Sara (Co-author) / Jehn, Megan (Thesis director) / Adams, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The SARS-CoV-2 (Covid-19) virus has had severe impacts on college students' ways of life. To examine how students were coping and perceiving the Covid-19 pandemic, a secondary analysis of an online survey across the three Arizona public universities investigated students’ knowledge about Covid-19, engagement with preventive strategies, pandemic preparedness and gauged their risk-perception. Results from our analysis indicate that the students were knowledgeable about Covid-19 and were changing their habits and engaging with preventive measures. Results further suggest that students were prepared for the pandemic in terms of resources and were exhibiting high-risk perceptions. The data also revealed that students who were being cautious and engaging with preventive behaviors had a higher risk-perception than individuals who were not. As for individuals who were prepared for the pandemic in terms of supplies, their risk perception was similar to those who did not have supplies. Individuals who were prepared and capable of providing a single caretaker to tend to their sick household members and isolate them in a separate room had a higher risk perception than those who could not. These results can help describe how college students will react to a future significant event, what resources students may be in need of, and how universities can take additional steps to keep their students safe and healthy. The results from this study and recommendations will provide for a stronger and more understanding campus community during times of distress and can improve upon already established university protocols for health crises and even natural disasters.
ContributorsShaikh, Sara (Co-author) / Naqvi, Avina (Co-author) / Jehn, Megan (Thesis director) / Adams, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05