Matching Items (314)
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 health benefits of physical activity are widely accepted. Emerging research also indicates that sedentary behaviors can carry negative health consequences regardless of physical activity level. This dissertation explored four projects that examined measurement properties of physical activity and sedentary behavior monitors. Project one identified the oxygen costs of four other care activities in seventeen adults. Pushing a wheelchair and pushing a stroller were identified as moderate-intensity activities. Minutes spent engaged in these activities contribute towards meeting the 2008 Physical Activity Guidelines. Project two identified the oxygen costs of common cleaning activities in sixteen adults. Mopping a floor was identified as moderate-intensity physical activity, while cleaning a kitchen and cleaning a bathtub were identified as light-intensity physical activity. Minutes spent engaged in mopping a floor contributes towards meeting the 2008 Physical Activity Guidelines. Project three evaluated the differences in number of minutes spent in activity levels when utilizing different epoch lengths in accelerometry. A shorter epoch length (1-second, 5-seconds) accumulated significantly more minutes of sedentary behaviors than a longer epoch length (60-seconds). The longer epoch length also identified significantly more time engaged in light-intensity activities than the shorter epoch lengths. Future research needs to account for epoch length selection when conducting physical activity and sedentary behavior assessment. Project four investigated the accuracy of four activity monitors in assessing activities that were either sedentary behaviors or light-intensity physical activities. The ActiGraph GT3X+ assessed the activities least accurately, while the SenseWear Armband and ActivPAL assessed activities equally accurately. The monitor used to assess physical activity and sedentary behaviors may influence the accuracy of the measurement of a construct.
ContributorsMeckes, Nathanael (Author) / Ainsworth, Barbara E (Thesis advisor) / Belyea, Michael (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Arizona State University (Publisher)
Created2012
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
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated in this four-treatment crossover trial. All subjects participated in four trials, each taking place over three days. On the evening of the first day, subjects were fitted with a continuous glucose monitor (CGM). On the second day, subjects were fitted with an ambulatory blood pressure monitor (ABP) and underwent one of the following four conditions in a randomized order: 1) 30-min: 30 minutes of continuous exercise at 60 - 70% VO2peak; 2) Mod 2-min: twenty-one 2-min bouts of walking at 3 mph performed once every 20 minutes; 3) HI 2-min: eight 2-min bouts of walking at maximal incline performed once every hour; 4) Control: a no exercise control condition. On the morning of the third day, the CGM and ABP devices were removed. All meals were standardized during the study visits. Linear mixed models were used to compare mean differences in glucose and blood pressure regulation between the four trials. Results: Glucose concentrations were significantly lower following the 30-min (91.1 ± 14.9 mg/dl), Mod 2-min (93.7 ± 19.8 mg/dl) and HI 2-min (96.1 ± 16.4 mg/dl) trials as compared to the Control (101.1 ± 20 mg/dl) (P < 0.001 for all three comparisons). The 30-min trial was superior to the Mod 2-min, which was superior to the HI 2-min trial in lowering blood glucose levels (P < 0.001 and P = 0.003 respectively). Only the 30-min trial was effective in lowering systolic ABP (124 ± 12 mmHg) as compared to the Control trial (127 ± 14 mmHg; P < 0.001) for up to 11 hours post exercise. Conclusion: Performing frequent short (i.e., 2 minutes) bouts of moderate or high intensity exercise may be a viable alternative to traditional continuous exercise in improving glucose regulation. However, 2-min bouts of exercise are not effective in reducing ambulatory blood pressure in healthy adults.
ContributorsBhammar, Dharini Mukeshkumar (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Buman, Matthew (Committee member) / Swan, Pamela (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2013
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 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
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 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
Description
Eccentric muscle action (ECC) occurs when the force exerted by a working muscle is less than that of an outside resistance. This is characterized by muscle lengthening, despite actin-myosin crossbridge formation. Research has indicated that muscles acting eccentrically are capable of producing more force when compared to muscles acting concentrically. Further, research has shown ECC muscle actions may have different fatigue patterns that CON actions. The purpose of this study was to determine if a) ECC bench press yields greater strength than concentric (CON) as measured by one-repetition maximum (1RM), b) there is a difference between the number of repetitions that can be completed concentrically and eccentrically under the same relative intensities of 1RM (90%, 80%, 70%, 60%), c) a prediction model may be able to predict ECC 1RM from CON 1RM or CON repetitions to fatigue. For this study, 30 healthy males (age = 24.63 + 5.6 years) were tested for 1RM in CON and ECC bench press, as well as the number of repetitions they were able to complete at various intensities of mode-specific 1RM. A mechanical hoist was affixed to a gantry crane and placed over a standard weightlifting bench. The hoist was connected to 45lb plates that were loaded on a standard barbell, which allowed for mechanical raising and lowering of the barbell. For CON repetitions, the weight was mechanically lowered to the chest and the participant pressed it up. For ECC repetitions, the weight was mechanically raised and the participant lowered it. Paired t-tests showed that ECC 1RM was significantly (p < 0.05) greater than CON 1RM (ECC =255.17 + 68.37lbs, CON = 205.83 + 58.43lbs). There was a significant difference (p < 0.05) between the number of repetitions completed at 90% 1RM (CON = 4.57 + 2.21 repetitions, ECC = 7.67 + 3.24 repetitions). There were no differences in repetitions completed at any other intensity 1RM. CON 1RM and the number of repetitions completed with two different absolute loads (130-150lbs and 155-175lbs) concentrically and eccentrically were valid predictors of ECC 1RM. These data indicate that ECC actions yield increased force capabilities than CON actions, there is no difference in the rate of the fatigue, and ECC 1RM may be predicted from various CON tests.
ContributorsKelly, Stephen B., Jr (Author) / Hooker, Steven (Thesis advisor) / Brown, Lee (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Swan, Pamela (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
As the prevalence of childhood obesity in the United States rises, opportunities for children to be physically active become more vital. One opportunity for physical activity involves children walking to and from school. However, children that live in areas with a pedestrian-unfriendly built environment and a low degree of walkability are less likely to be physically active and more likely to be overweight. The purpose of this study was to study walking routes from schools in low-income neighborhoods in Southwestern United States to a local community center. Walking routes from the three study schools (South Mountain High School, Percy Julian Middle School, and Rose Linda Elementary School) were determined by distance, popularity, and the presence of a major thoroughfare. Segments and intersections, which formed the routes, were randomly selected from each school's buffer region. The walking routes as a whole, along with the segments and intersections, were audited and scored using built environment assessments tools: MAPS, PEQI and Walkability Checklist. These scores were utilized to develop interactive mapping tools to visualize the quality of the routes, segments and intersections and identify areas for improvement. Results showed that the routes from Percy Julian to the Kroc Center were, overall, rated higher than routes from the other two schools. The highest scoring route, from the seven routes studied, was route 2 from Percy Julian to the Kroc Center along Broadway Road. South Mountain High School was overall the worst starting point for walking to the Kroc Center as those three walking routes were graded as the least walkable. Possible areas for improvement include installing traffic calming features along major thoroughfares and reducing the perceived risk to pedestrian safety by beautifying the community by planting greenery. Future directions include studying the built environment in South Phoenix communities that surround the Kroc Center.
ContributorsZeien, Justin Lee (Author) / Buman, Matthew (Thesis director) / Hekler, Eric (Committee member) / Fellows, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05