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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.,

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
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Description
The purpose of this pilot randomized control trial was to test the initial efficacy of a 10 week social cognitive theory (SCT)-based intervention to reduce workplace sitting time (ST). Participants were currently employed adults with predominantly sedentary occupations (n=24) working in the Greater Phoenix area in 2012-2013. Participants wore an

The purpose of this pilot randomized control trial was to test the initial efficacy of a 10 week social cognitive theory (SCT)-based intervention to reduce workplace sitting time (ST). Participants were currently employed adults with predominantly sedentary occupations (n=24) working in the Greater Phoenix area in 2012-2013. Participants wore an activPAL (AP) inclinometer to assess postural allocation (i.e., sitting vs. standing) and Actigraph accelerometer (AG) to assess sedentary time for one week prior to beginning and immediately following the completion of the 10 week intervention. Self-reported measures of sedentary time were obtained via two validated questionnaires for overall (International Physical Activity Questionnaire [IPAQ]) and domain specific sedentary behaviors (Sedentary Behavior Questionnaire [SBQ]). SCT constructs were also measured pre and post via adapted physical activity questionnaires. Participants were randomly assigned to receive either (a) 10 weekly social cognitive-based e-newsletters focused on reducing workplace ST; or (b) similarly formatted 10 weekly e-newsletters focusing on health education. Baseline adjusted Analysis of Covariance statistical analyses were used to examine differences between groups in time spent sitting (AP) and sedentary (AG) during self-reported work hours from pre- to post- intervention. Both groups decreased ST and AG sedentary time; however, no significant differences were observed. SCT constructs also did not change significantly between pretest and post test in either group. These results indicate that individualized educational approaches to decreasing workplace sitting time may not be sufficient for observing long term change in behaviors. Future research should utilize a larger sample, measure main outcomes more frequently, and incorporate more environmental factors throughout the intervention.
ContributorsGordon, Amanda (Author) / Buman, Matthew (Thesis advisor) / Der Ananian, Cheryl (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
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Description
INTRODUCTION: Exercise performed at moderate to vigorous intensities has been shown to generate a post exercise hypotensive response. Whether this response is observed with very low exercise intensities is unclear. PURPOSE: To compare post physical activity ambulatory blood pressure (ABP) response to a single worksite walking day and a normal

INTRODUCTION: Exercise performed at moderate to vigorous intensities has been shown to generate a post exercise hypotensive response. Whether this response is observed with very low exercise intensities is unclear. PURPOSE: To compare post physical activity ambulatory blood pressure (ABP) response to a single worksite walking day and a normal sedentary work day in pre-hypertensive adults. METHODS: Participants were 7 pre-hypertensive (127 + 8 mmHg / 83 + 8 mmHg) adults (3 male, 4 female, age = 42 + 12 yr) who participated in a randomized, cross-over study that included a control and a walking treatment. Only those who indicated regularly sitting at least 8 hours/day and no structured physical activity were enrolled. Treatment days were randomly assigned and were performed one week apart. Walking treatment consisted of periodically increasing walk time up to 2.5 hours over the course of an 8 hour work day on a walking workstation (Steelcase Company, Grand Rapids, MI). Walk speed was set at 1 mph. Participants wore an ambulatory blood pressure cuff (Oscar 2, SunTech Medical, Morrisville, NC) for 24-hours on both treatment days. Participants maintained normal daily activities on the control day. ABP data collected from 9:00 am until 10:00 pm of the same day were included in statistical analyses. Linear mixed models were used to detect differences in systolic (SBP) and diastolic blood pressure (DBP) by treatment condition over the whole day and post workday for the time periods between 4 -10 pm when participants were no longer at work. RESULTS:BP was significantly lower in response to the walking treatment compared to the control day (Mean SBP 126 +7 mmHg vs.124 +7 mmHg, p=.043; DBP 80 + 3 mmHg vs. 77 + 3 mmHg, p = 0.001 respectively). Post workday (4:00 to 10:00 pm) SBP decreased 3 mmHg (p=.017) and DBP decreased 4 mmHg (p<.001) following walking. CONCLUSION: Even low intensity exercise such as walking on a walking workstation is effective for significantly reducing acute BP when compared to a normal work day.
ContributorsZeigler, Zachary (Author) / Swan, Pamela (Thesis advisor) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2013
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Description
This study examines cognitive and motor function in typical older adults following acute exercise. Ten older adults (Mage = 65.1) completed a single session of assisted cycling (AC) (i.e., exercise accomplished through the use of a motor), voluntary cycling (VC) (self-selected cadence), and a no cycling (NC) control group.

This study examines cognitive and motor function in typical older adults following acute exercise. Ten older adults (Mage = 65.1) completed a single session of assisted cycling (AC) (i.e., exercise accomplished through the use of a motor), voluntary cycling (VC) (self-selected cadence), and a no cycling (NC) control group. These sessions were randomized and separated by approximately one week. Both ACT and VC groups rode a stationary bicycle for 30-minutes each session. These sessions were separated by at least two days. Participants completed cognitive testing that assessed information processing and set shifting and motor testing including gross and fine motor performance at the beginning and at the end of each session. Consistent with our hypothesis concerning manual dexterity, the results showed that manual dexterity improved following the ACT session more than the VC or NC sessions. Improvements in set shifting were also found for the ACT session but not for the VC or NC sessions. The results are interpreted with respect to improvements in neurological function in older adults following acute cycling exercise. These improvements are balance, manual dexterity, and set shifting which have a positive effects on activities of daily living; such as, decrease risk of falls, improve movements like eating and handwriting, and increase ability to multitask.
ContributorsSemken, Keith (Author) / Ringenbach, Shannon (Thesis advisor) / Der Ananian, Cheryl (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2015
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Description
The purpose of this study was to examine whether a workplace environmental intervention would improve work-related outcomes including productivity, presenteeism and cognition. The secondary aim was to investigate whether work-related outcomes are correlated to observed changes in sitting time, physical activity, and sleep. The study was introduced as part of

The purpose of this study was to examine whether a workplace environmental intervention would improve work-related outcomes including productivity, presenteeism and cognition. The secondary aim was to investigate whether work-related outcomes are correlated to observed changes in sitting time, physical activity, and sleep. The study was introduced as part of a naturalistic environmental change in which university staff and faculty were relocated into a new building (n=23). The comparison group consisted of university staff within the same college with no imminent plans to re-locate during the intervention period; there were no environmental changes to this workplace (n =10). Participants wore two behavioral monitoring devices, activPAL and GeneActiv, for 7 consecutive days at two time points (immediately prior and 16 weeks following the office relocation). Measures of productivity and presenteeism were obtained via four validated questionnaires and participants underwent cognitive performance testing. Baseline adjusted analysis of covariance statistical analyses were used to examine differences between groups in work-related outcomes. A residual analysis in regression was conducted to determine the differences between observed changes in sitting time, physical activity and sleep, and work-related outcomes. The results showed that a reduction in work hour sitting time was not detrimental to work related outcomes. Decreased sitting was observed to potentially improve presenteeism and absenteeism. Additionally, physical activity was shown to modestly improve productivity, presenteeism and absenteeism. Poor sleep patterns were associated with work impairment and increased absenteeism.
ContributorsPark, Anna (Author) / Buman, Matthew (Thesis advisor) / Crespo, Noe (Committee member) / Chisum, Jack (Committee member) / Arizona State University (Publisher)
Created2014
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Description
PURPOSE: This study aimed to identify whether increased Pokémon GO use resulted in increased daily steps, compared to days when an individual did not play. In addition, this study examined Pokémon GO as a use case for for the study of gamification, particularly whether traditionally identified game mechanics in gamification

PURPOSE: This study aimed to identify whether increased Pokémon GO use resulted in increased daily steps, compared to days when an individual did not play. In addition, this study examined Pokémon GO as a use case for for the study of gamification, particularly whether traditionally identified game mechanics in gamification literature were successfully identified as elements players enjoy when playing Pokémon GO. METHODS: A mixed methods approach, with 17 participants taking part in a daily physical activity tracking study and 14 participants participating in semi-structured interviews. In the use study, participant steps were tracked for one week using the Apple Health Kit application, and participants were also asked to provide daily answers to a variety of questions assessing game preferences and daily use of Pokémon GO - using the application called PACO. The semi-structured interviews examined self-reported physical activity, and asked questions pertaining to use of Pokémon GO, such as motivation to play. RESULTS: Results assessed by t-test indicate a small but non-significant trend towards increased steps taken on days when a participant played vs. did not play (t(72)=- .56, p=.57, mplay=5,0153220, mnonplay=4,5152,959). This was confirmed with a mixed model test showing that when controlling for time and participant’s baseline level of steps, there was no significant effect on steps/day. Results from the daily surveys and also the semi-structured interviews, indicated that nostalgia (i.e., catching ones’ favorite childhood Pokémon), was a strong motivator for many to play the game, which was counter to theoretical expectations. In line with previous theory, results suggested that operant conditioning principles appeared to be at work in terms of fostering game play use. DISCUSSION: Results of this study, which was a primarily hypothesis generating endeavor, indicated possible trends toward increased steps on days when a person plays Pokémon G), but - with such a small sample, and short-term length of study - no firm conclusions can be drawn. Further, results indicate the particular value of nostalgia as a driver towards game play for Pokémon GO.
ContributorsBiel, Alexander M (Author) / Hekler, Eric (Thesis advisor) / Ainsworth, Barbara (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2016
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Description
Pitchers are a vital part of the game of baseball and may account for up to two-thirds of the variance in win percentage. As they rise through the ranks of competition, physical skill set becomes less of a factor when compared to mentality. Pitchers are the “first line of defense”

Pitchers are a vital part of the game of baseball and may account for up to two-thirds of the variance in win percentage. As they rise through the ranks of competition, physical skill set becomes less of a factor when compared to mentality. Pitchers are the “first line of defense” for keeping opponents from having an opportunity to score, as well as for holding onto their own team’s lead. Baseball pitchers not only face pressure to perform, but also experience stress from factors such as low pay, adjusting to higher levels of competition, and internal team competition for a limited number of spots. Athletes are often resistant to seeking aid from sport psychologists and often turn to unfavorable means to cope (i.e. drugs/alcohol, excessive exercise) with stress instead. Meditation has been shown to have beneficial effects on psychological factors associated with performance including emotional regulation, anxiety, confidence, focus, and mindfulness. Mobile applications have become a popular means of delivering mindfulness. The purpose of this study was to determine the feasibility and preliminary effectiveness of delivering a mindful meditation intervention using a mobile meditation application to improve psychological factors associated with performance (i.e. emotional regulation, anxiety (somatic and cognitive), confidence, focus, mindfulness) to minor league baseball pitchers. Pitchers in instructional league (Phase one) and off season (Phase two) were asked to meditate daily for 10-minutes each day for three weeks (Phase one) and eight weeks (Phase two). Pitchers were asked to complete self-report questionnaires and satisfaction surveys at pre- and post-intervention. Pitchers in phase one reported enjoying meditation, had improvements in self-confidence and sport confidence, and reported moderate decreases in cognitive anxiety and concentration disruption. Pitchers in phase two also enjoyed meditating (94.7%) and had improvements in self-confidence and moderate decreases in somatic anxiety. Low adherence due to timing (off-season) of intervention may have been a contributing factor to fewer outcomes. Future research should explore the feasibility and effectiveness of implementing meditation during the baseball season.
ContributorsDowling, Tiffany (Author) / Huberty, Jennifer (Thesis advisor) / Ransdell, Lynda (Committee member) / Buman, Matthew (Committee member) / Michel, Jesse (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine

Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine the functional importance of Mycobacterium tuberculosis Fic and its putative antitoxin protein, Rv3642c. Using M. tuberculosis H37Rv genetic deletion mutants, fic and Rv3642c were demonstrated to promote intracellular survival in human THP-1 macrophage-like cells. Unlike other Fic toxins, of Fic toxin-antitoxin systems, Fic did not inhibit bacterial growth in vitro in the absence of Rv3642c. Notably, Fic demonstrated in vitro AMPylation of a THP-1 cell extract protein as shown by immunodetection. Fic also exhibited auto-AMPylation activity. Interestingly, a mutation of the conserved histidine in the Fic domain motif, a residue previously shown to be critical for AMPylation, had no effect on Fic-mediated ATP hydrolysis or AMPylation activity. Rv3642c was demonstrated to form a complex with Fic when co-expressed in Escherichia coli, indicating a toxin-antitoxin interaction. Screening M. tuberculosis protein fractions and culture filtrate with α-Fic and α-Rv3642c rabbit antisera did not detect monomers of Fic or Rv3642c, thus the cellular localization of Fic and the Rv3642c-Fic complex remains unclear. The results of this study provide insight into the function of M. tuberculosis Fic, and suggest that Fic and Rv3642c are important for M. tuberculosis survival in the intracellular macrophage environment. Furthermore, these findings challenge the current dogma that Fic domain catalysis is dependent on the conserved histidine of the Fic motif.
ContributorsLaMarca, Ryan (Author) / Haydel, Shelley (Thesis advisor) / Lake, Douglas (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how each activity may affect cardiometabolic biomarkers. The objective of this study was to examine data from the BeWell24 studies to

Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how each activity may affect cardiometabolic biomarkers. The objective of this study was to examine data from the BeWell24 studies to evaluate the relationship between objectively measured physical activity and sedentary behaviors and cardiometabolic biomarkers in middle age adults, while also determining if sleep quality and duration mediates this relationship. A group of inactive participants (N = 29, age = 52.1 ± 8.1 years, 38% female) with increased risk for cardiometabolic disease were recruited to participate in BeWell24, a trial testing the impact of a lifestyle-based, multicomponent smartphone application targeting sleep, sedentary, and more active behaviors. During baseline, interim (4 weeks), and posttest visits (8 weeks), biomarker measurements were collected for weight (kg), waist circumference (cm), glucose (mg/dl), insulin (uU/ml), lipids (mg/dl), diastolic and systolic blood pressures (mm Hg), and C reactive protein (mg/L). Participants wore validated wrist and thigh sensors for one week intervals at each time point to measure sedentary behavior, physical activity, and sleep outcomes. Long bouts of sitting time (>30 min) significantly affected triglycerides (beta = .15 (±.07), p<.03); however, no significant mediation effects for sleep quality or duration were present. No other direct effects were observed between physical activity measurements and cardiometabolic biomarkers. The findings of this study suggest that reductions in long bouts of sitting time may support reductions in triglycerides, yet these effects were not mediated by sleep-related improvements.
ContributorsLanich, Boyd (Author) / Buman, Matthew (Thesis advisor) / Ainsworth, Barbara (Committee member) / Huberty, Jennifer (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major

Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major disruption to spaceflight missions. The potable water system on the International Space Station (ISS) uses recycled wastewater purified by multiple processes so it is safe for astronaut consumption and personal hygiene. However, despite stringent antimicrobial treatments, multiple bacterial species and biofilms have been recovered from this potable water system. This finding raises concern for crew health risks, vehicle operations and ECLSS system integrity during exploration missions. These concerns are further heightened given that 1) potential pathogens have been isolated from the ISS potable water system, 2) the immune response of astronauts is blunted during spaceflight, 3) spaceflight induces unexpected alterations in microbial responses, including growth and biofilm formation, antimicrobial resistance, stress responses, and virulence, and 4) different microbial phenotypes are often observed between reductionistic pure cultures as compared to more complex multispecies co-cultures, the latter of which are more representative of natural environmental conditions. To advance the understanding of the impact of microgravity on microbial responses that could negatively impact spacecraft ECLSS systems and crew health, this study characterized a range of phenotypic profiles in both pure and co-cultures of bacterial isolates collected from the ISS potable water system between 2009 and 2014. Microbial responses profiled included population dynamics, resistance to silver, biofilm formation, and in vitro colonization of intestinal epithelial cells. Growth characteristics and antibiotic sensitivities for bacterial strains were evaluated to develop selective and/or differential media that allow for isolation of a pure culture from co-cultures, which was critical for the success of this study. Bacterial co-culture experiments were performed using dynamic Rotating Wall Vessel (RWV) bioreactors under spaceflight analogue (Low Shear Modeled Microgravity/LSMMG) and control conditions. These experiments indicated changes in fluid shear have minimal impact on strain recovery. The antimicrobial efficacy of silver on both sessile co-cultures, grown on 316L stainless steel coupons, and planktonic co-cultures showed that silver did not uniformly reduce the recovery of all strains; however, it had a stronger antimicrobial effect on biofilm cultures than planktonic cultures. The impact of silver on the ability of RWV cultured planktonic and biofilm bacterial co-cultures to colonize human intestinal epithelial cells showed that, those strains which were impacted by silver treatment, often increased adherence to the monolayer. Results from these studies provide insight into the dynamics of polymicrobial community interactions, biofilm formation and survival mechanisms of ISS potable water isolates, with potential application for future design of ECLSS systems for sustainable human space exploration.
ContributorsKing, Olivia G (Author) / Nickerson, Cheryl (Thesis advisor) / Barrila, Jennifer (Committee member) / Ott, C (Committee member) / Yang, Jiseon (Committee member) / Arizona State University (Publisher)
Created2019