Matching Items (55)
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
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
Lonsdaleite, also called hexagonal diamond, has been widely used as a marker of asteroidal impacts. It is thought to play a central role during the graphite-to-diamond transformation, and calculations suggest that it possesses mechanical properties superior to diamond. However, despite extensive efforts, lonsdaleite has never been produced or described as a separate, pure material. Here we show that defects in cubic diamond provide an explanation for the characteristic d-spacings and reflections reported for lonsdaleite. Ultrahigh-resolution electron microscope images demonstrate that samples displaying features attributed to lonsdaleite consist of cubic diamond dominated by extensive {113} twins and {111} stacking faults. These defects give rise to nanometre-scale structural complexity. Our findings question the existence of lonsdaleite and point to the need for re-evaluating the interpretations of many lonsdaleite-related fundamental and applied studies.
ContributorsNemeth, Peter (Author) / Garvie, Laurence (Author) / Aoki, Toshihiro (Author) / Dubrovinskaia, Natalia (Author) / Dubrovinsky, Leonid (Author) / Buseck, Peter (Author) / Department of Chemistry and Biochemistry (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Earth and Space Exploration (Contributor) / Center for Meteorite Studies (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / LeRoy Eyring Center for Solid State Science (Contributor) / School of Molecular Sciences (Contributor)
Created2014-11-01
Description
Spaceflight and spaceflight analogue culture enhance the virulence and pathogenesis-related stress resistance of the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). This is an alarming finding as it suggests that astronauts may have an increased risk of infection during spaceflight. This risk is further exacerbated as multiple studies indicate that spaceflight negatively impacts aspects of the immune system. In order to ensure astronaut safety during long term missions, it is important to study the phenotypic effects of the microgravity environment on a range of medically important microbial pathogens that might be encountered by the crew. This ground-based study uses the NASA-engineered Rotating Wall Vessel (RWV) bioreactor as a spaceflight analogue culture system to grow bacteria under low fluid shear forces relative to those encountered in microgravity, and interestingly, in the intestinal tract during infection. The culture environment in the RWV is commonly referred to as low shear modeled microgravity (LSMMG). In this study, we characterized the stationary phase stress response of the enteric pathogen, Salmonella enterica serovar Enteritidis (S. Enteritidis), to LSMMG culture. We showed that LSMMG enhanced the resistance of stationary phase cultures of S. Enteritidis to acid and thermal stressors, which differed from the LSSMG stationary phase response of the closely related pathovar, S. Typhimurium. Interestingly, LSMMG increased the ability of both S. Enteritidis and S. Typhimurium to adhere to, invade into, and survive within an in vitro 3-D intestinal co-culture model containing immune cells. Our results indicate that LSMMG regulates pathogenesis-related characteristics of S. Enteritidis in ways that may present an increased health risk to astronauts during spaceflight missions.
ContributorsKoroli, Sara (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, C. Mark (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The International Space Station (ISS) utilizes recycled water for consumption, cleaning and air humidity control. The Environmental Control and Life Support Systems (ECLSS) have been rigorously tested at the NASA Johnson Space Center. Despite the advanced engineering of the water recovery system, bacterial biofilms have been recovered from this potable water source. Microbial contamination of potable water poses a potential threat to crew members onboard the ISS. Because astronauts have been found to have compromised immune systems, bacterial strains that would not typically be considered a danger must be carefully studied to better understand the mechanisms enabling their survival, including polymicrobial interactions. The need for a more thorough understanding of the effect of spaceflight environment on polymicrobial interactions and potential impact on crew health and vehicle integrity is heightened since 1) several potential pathogens have been isolated from the ISS potable water system, 2) spaceflight has been shown to induce unexpected alterations in microbial responses, and 3) emergent phenotypes are often observed when multiple bacterial species are co- cultured together, as compared to pure cultures of single species. In order to address these concerns, suitable growth media are required that will not only support the isolation of these microbes but also the ability to distinguish between them when grown as mixed cultures. In this study, selective and/or differential media were developed for bacterial isolates collected from the ISS potable water supply. In addition to facilitating discrimination between bacteria, the ideal media for each strain was intended to have a 100% recovery rate compared to traditional R2A media. Antibiotic and reagent susceptibility and resistance tests were conducted for the purpose of developing each individual medium. To study a wide range of targets, 12 antibiotics were selected from seven major classes, including penicillin, cephalosporins, fluoroquinolones, aminoglycosides, glycopeptides/lipoglycopeptides, macrolides/lincosamides/streptogramins, tetracyclines, in addition to seven unclassified antibiotics and three reagents. Once developed, medium efficacy was determined by means of growth curve experiments. The development of these media is a critical step for further research into the mechanisms utilized by these strains to survive the harsh conditions of the ISS water system. Furthermore, with an understanding of the complex nature of these polymicrobial communities, specific contamination targeting and control can be conducted to reduce the risk to crew members. Understanding these microbial species and their susceptibilities has potential application for future NASA human explorations, including those to Mars.
ContributorsKing, Olivia Grace (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.
ContributorsVu, Christian-Alexander (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
Description
Breast cancer is one of the leading causes of cancer-related deaths among women in the United States. Uninsured women are less likely to receive breast cancer screenings, more likely to be diagnosed at an advanced stage, and more likely to have poorer outcomes following a breast cancer diagnosis (Abdelsattar et al., 2016; Akinlotan et al., 2021; Ko et al., 2020; & Ntiri et al., 2018). Women in underserved communities often experience socioeconomic barriers which impact obtaining preventative screenings, such as mammograms. Lack of patient navigation, transportation, and financial concerns interfere with obtaining breast cancer screening (Akinlotan et al., 2021 & Miller et al., 2019). Through the intervention of mobile mammography, uninsured women in underserved communities can be reached and access to screening mammograms can be achieved (Stanley et al., 2017 & Vang et al., 2018). Two mobile mammography events were hosted at the project site which provided 35 women with screening mammograms. All scheduled mammogram time slots at the events were filled and completed. Offering mobile mammography to this population has the potential to increase breast cancer surveillance.
ContributorsGlessner-Vallee, Paula (Author) / Santerre, Jennifer (Thesis advisor) / College of Nursing and Health Innovation (Contributor)
Created2023-04-26
Description
Introduction: The objective of this study is to emphasize the significance of exclusive breastfeeding (EB) and investigate methods to encourage and sustain it within a hospital environment. Using the self-efficacy theory, the study seeks to improve the current support system for breastfeeding mothers and their families. Methods: The project was approved by the university IRB and facility IRB; guidelines were maintained. The project takes place in a non-profit organization in the southwestern United States. Education was conducted at a required staff meeting for Women and Infant Services (WIS) floor about supporting breastfeeding mothers. A pre- and post-education Breastfeeding Knowledge Scale (BKS) survey was performed, effectiveness was measured using a two-tailed t-test. The reliability of the BKS scale is 0.83 and the validity of the scale is reported to be strong. The hospital measures the EB rates of patients that are greater than 37 weeks gestation without need for neonatal intensive unit care and the mom requests to breastfeed. Results: The goal was 42% rate of EB in the first 48 hours after birth. After education the average rate of EB was 39.6%, lower than the goal but higher than the 33.7% rate before education. A two-tailed paired sample t-test (n=27) was used for BKS and the results were significant based on an alpha value; thus, showing significant knowledge gain. Conclusion: Consistent staff education improves breastfeeding support for moms in the hospital, leading to successful exclusive breastfeeding. This project benefits various settings, such as pediatric, postpartum, labor and delivery, and pediatric offices.
ContributorsHudson, Jennifer (Author) / Esperas, Amanda (Thesis advisor) / College of Nursing and Health Innovation (Contributor)
Created2023-04-26
Description
Introduction: Depression screening in the pediatric setting is a crucial part of the adolescent's examination. A standardized screening tool and protocol streamlines the process of assessing adolescents and minimizes the chances of serious mental health disorders going undetected and untreated. Evaluation of current evidence demonstrates the use of a standardized tool improves detection, diagnosis, and management of depression and other mental health illnesses.
Method: The Patient Health Questionnaire—modified for adolescents (PHQ9-A) was administered to all eligible adolescents, ages 12-18, during an annual well visit for a period of 6 weeks. Lewin's Change Theory guided a system change in the electronic health record, and the questionnaire results were documented and provided to the pediatric provider at the time of the appointment. A chart review was conducted to determine whether all eligible patients were administered the questionnaire and if a depression diagnosis or mental health referral had been made.
Results: Out of 76 eligible well visits, 65 (86%) patients completed the PHQ9-A. The average score was 5.29 (SD = 6.49) with a maximum score of 25. Out of those that completed screening, 11 (17%) had a positive PHQ9-A score resulting in 8 referrals to mental health services and 2 mental health diagnoses in the clinic.
ContributorsCoomer, Meagan (Author) / Rauton, Monica (Thesis advisor) / College of Nursing and Health Innovation (Contributor)
Created2023-04-27