Matching Items (99)
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
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
Introduction/Purpose: the purpose of this study was to explore the perception of care after stillbirth and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief in women of racial/ethnic minority who have experienced stillbirth.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
ContributorsArvayo, Jordan Michelle (Author) / Huberty, Jennifer (Thesis director) / Hoffner, Kristin (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This study examined the effect of an 8-week exercise intervention on functional exercise capacity in adolescents with Down syndrome (DS). Forty participants were randomly assigned to one of three groups: assisted cycling (ACT) (n = 17) where participants experienced at least a 35% increase in their voluntary cycling speed through the use of a motor, voluntary cycling (VC) (n = 15) where participants cycled at a self-selected cadence, and no cycling (NC) (n = 8) where participants did not participate in any cycling intervention. In each cycling intervention, each participant completed three, 30 minute cycling sessions per week for a total of eight weeks. The Six-Minute Walk Test (6MWT) was administered prior to and after the 8-week intervention in pre-test and post-test assessment sessions, respectively. Our hypothesis was somewhat supported in that functional exercise capacity improved after ACT as measured by an increase in total number of laps walked, total distance walked, and average walking speed during the 6MWT, when compared to VC or NC.
ContributorsCook, Megan Rey (Author) / Ringenbach, Shannon (Thesis director) / Huberty, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (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
Objective: Fewer than 50% of female college freshmen meet physical activity (PA) guidelines. Innovative approaches that help college women increase their PA are warranted. The study purpose was to pilot test a magazine-based discussion group for improving PA, self-worth, and nutrition behaviors in freshmen college females. Method: Thirty-seven women (18-20 years) were randomized to intervention (n=17) and control (n=20) groups. The intervention group participated in an 8-week magazine-based discussion group adapted from a previously tested social cognitive theory based intervention, Fit Minded. Excerpts from a popular women's health magazine were discussed during weekly meetings incorporating PA, self-worth and nutrition education. The control group did not attend meetings, but received the magazines. Outcomes and feasibility measures included: self-reported PA, general self-worth, knowledge self-worth, self-efficacy, social support, and daily fruits, vegetables, junk food, sugar-sweetened beverage consumption. Results: Twelve participants from the intervention group attended more than 75% of meetings. A time effect was observed for PA (p=0.001) and family social support (p=0.002). Time x group effects were observed for PA (p=0.001), general self-worth (p=0.04), knowledge self-worth (p=0.03), and daily sugar-sweetened beverage consumption (p=0.03), with the intervention group reporting greater increases in PA, general self-worth and knowledge self-worth and greater decreases in daily sugar-sweetened beverage consumption. Although not significant, the intervention group demonstrated positive trends in self-efficacy, friend social support and fruit and veggie consumption as compared to the control group. Conclusion: A magazine-based discussion group may provide a promising platform to improve PA, self-worth and nutrition behaviors in female college freshmen.
ContributorsPellitteri, Katelyn (Author) / Huberty, Jennifer (Thesis director) / Bruening, Meg (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Social Transformation (Contributor) / Sandra Day O'Connor College of Law (Contributor)
Created2014-05
Description
Critical flicker fusion thresholds (CFFTs) describe when quick amplitude modulations of a light source become undetectable as the frequency of the modulation increases and are thought to underlie a number of visual processing skills, including reading. Here, we compare the impact of two vision-training approaches, one involving contrast sensitivity training and the other directional dot-motion training, compared to an active control group trained on Sudoku. The three training paradigms were compared on their effectiveness for altering CFFT. Directional dot-motion and contrast sensitivity training resulted in significant improvement in CFFT, while the Sudoku group did not yield significant improvement. This finding indicates that dot-motion and contrast sensitivity training similarly transfer to effect changes in CFFT. The results, combined with prior research linking CFFT to high-order cognitive processes such as reading ability, and studies showing positive impact of both dot-motion and contrast sensitivity training in reading, provide a possible mechanistic link of how these different training approaches impact reading abilities.
ContributorsZhou, Tianyou (Author) / Nanez, Jose (Author) / Zimmerman, Daniel (Author) / Holloway, Steven (Author) / Seitz, Aaron (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-10-26
Description
Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.
ContributorsYahata, Noriaki (Author) / Morimoto, Jun (Author) / Hashimoto, Ryuichiro (Author) / Lisi, Giuseppe (Author) / Shibata, Kazuhisa (Author) / Kawakubo, Yuki (Author) / Kuwabara, Hitoshi (Author) / Kuroda, Miho (Author) / Yamada, Takashi (Author) / Megumi, Fukuda (Author) / Imamizu, Hiroshi (Author) / Nanez, Jose (Author) / Takahashi, Hidehiko (Author) / Okamoto, Yasumasa (Author) / Kasai, Kiyoto (Author) / Kato, Nobumasa (Author) / Sasaki, Yuka (Author) / Watanabe, Takeo (Author) / Kawato, Mitsuo (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-04-14
Description
Background
The purpose of this study is to determine the feasibility of three widely used wearable sensors in research settings for 24 h monitoring of sleep, sedentary, and active behaviors in middle-aged women.
Methods
Participants were 21 inactive, overweight (M Body Mass Index (BMI) = 29.27 ± 7.43) women, 30 to 64 years (M = 45.31 ± 9.67). Women were instructed to wear each sensor on the non-dominant hip (ActiGraph GT3X+), wrist (GENEActiv), or upper arm (BodyMedia SenseWear Mini) for 24 h/day and record daily wake and bed times for one week over the course of three consecutive weeks. Women received feedback about their daily physical activity and sleep behaviors. Feasibility (i.e., acceptability and demand) was measured using surveys, interviews, and wear time.
Results
Women felt the GENEActiv (94.7 %) and SenseWear Mini (90.0 %) were easier to wear and preferred the placement (68.4, 80 % respectively) as compared to the ActiGraph (42.9, 47.6 % respectively). Mean wear time on valid days was similar across sensors (ActiGraph: M = 918.8 ± 115.0 min; GENEActiv: M = 949.3 ± 86.6; SenseWear: M = 928.0 ± 101.8) and well above other studies using wake time only protocols. Informational feedback was the biggest motivator, while appearance, comfort, and inconvenience were the biggest barriers to wearing sensors. Wear time was valid on 93.9 % (ActiGraph), 100 % (GENEActiv), and 95.2 % (SenseWear) of eligible days. 61.9, 95.2, and 71.4 % of participants had seven valid days of data for the ActiGraph, GENEActiv, and SenseWear, respectively.
Conclusion
Twenty-four hour monitoring over seven consecutive days is a feasible approach in middle-aged women. Researchers should consider participant acceptability and demand, in addition to validity and reliability, when choosing a wearable sensor. More research is needed across populations and study designs.
The purpose of this study is to determine the feasibility of three widely used wearable sensors in research settings for 24 h monitoring of sleep, sedentary, and active behaviors in middle-aged women.
Methods
Participants were 21 inactive, overweight (M Body Mass Index (BMI) = 29.27 ± 7.43) women, 30 to 64 years (M = 45.31 ± 9.67). Women were instructed to wear each sensor on the non-dominant hip (ActiGraph GT3X+), wrist (GENEActiv), or upper arm (BodyMedia SenseWear Mini) for 24 h/day and record daily wake and bed times for one week over the course of three consecutive weeks. Women received feedback about their daily physical activity and sleep behaviors. Feasibility (i.e., acceptability and demand) was measured using surveys, interviews, and wear time.
Results
Women felt the GENEActiv (94.7 %) and SenseWear Mini (90.0 %) were easier to wear and preferred the placement (68.4, 80 % respectively) as compared to the ActiGraph (42.9, 47.6 % respectively). Mean wear time on valid days was similar across sensors (ActiGraph: M = 918.8 ± 115.0 min; GENEActiv: M = 949.3 ± 86.6; SenseWear: M = 928.0 ± 101.8) and well above other studies using wake time only protocols. Informational feedback was the biggest motivator, while appearance, comfort, and inconvenience were the biggest barriers to wearing sensors. Wear time was valid on 93.9 % (ActiGraph), 100 % (GENEActiv), and 95.2 % (SenseWear) of eligible days. 61.9, 95.2, and 71.4 % of participants had seven valid days of data for the ActiGraph, GENEActiv, and SenseWear, respectively.
Conclusion
Twenty-four hour monitoring over seven consecutive days is a feasible approach in middle-aged women. Researchers should consider participant acceptability and demand, in addition to validity and reliability, when choosing a wearable sensor. More research is needed across populations and study designs.
ContributorsHuberty, Jennifer (Author) / Ehlers, Diane (Author) / Kurka, Jonathan (Author) / Ainsworth, Barbara (Author) / Buman, Matthew (Author) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-07-30