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- Genre: Doctoral Dissertation
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
Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and 3) changes in F&V consumption. In this two-arm randomized controlled trial, 64 adults who did not meet standard F&V recommendations were allocated to an intervention (n=33) or control group (n=31). Participants in the intervention group ranked 20 F&V-related behaviors according to their perceived likelihood of engagement in the behavior and their perception of the behavior’s efficacy in increasing F&V consumption. Participants in the intervention group were subsequently shown the list of 20 behaviors in order of their provided rankings, with the highest-ranked behaviors at the top, and were asked to choose a behavior they would like to perform daily for 4 weeks. The control group chose from a random-order list of the same 20 behaviors to adopt daily for 4 weeks. During the study period, text messages were sent to all participants 90 minutes before their reported bedtime to collect Yes/No data reflecting successful behavior engagement each day. The binary repeated-measures data collected from the text messages was analyzed using mixed-effects logistic regression, differences in attrition were assessed using log-rank analysis, and change scores in F&V consumption were compared between the two groups using the Man-Whitney U test. P<0.05 indicated significance. The rate of successful behavior adoption did not differ significantly between the two groups (b=0.09, 95%CI= -0.81, 0.98, p=0.85). The log rank test results indicated that there was no significant difference in attrition between the two groups (χ2=2.68, df=1, p=0.10). F&V consumption increased significantly over the 4 weeks in the total sample (Z=-5.86, p<0.001), but no differences in F&V change scores were identified between the control and intervention groups (Z=-0.21, p=0.84). The behavior-matching tool assessed in this study did not significantly improve behavior adoption, study attrition, or F&V intake over 4 weeks.
ContributorsCosgrove, Kelly Sarah (Author) / Wharton, Christopher (Thesis advisor) / Adams, Marc (Committee member) / DesRoches, Tyler (Committee member) / Grebitus, Carola (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023
Description
Background In the United States (US), first-year university students typically live on campus and purchase a meal plan. In general, meal plans allow the student a set number of meals per week or semester, or unlimited meals. Understanding how students’ use their meal plan, and barriers and facilitators to meal plan use, may help decrease nutrition-related issues.
Methods First-year students’ meal plan and residence information was provided by a large, public, southwestern university for the 2015-2016 academic year. A subset of students (n=619) self-reported their food security status. Logistic generalized estimating equations (GEEs) were used to determine if meal plan purchase and use were associated with food insecurity. Linear GEEs were used to examine several potential reasons for lower meal plan use. Logistic and Linear GEEs were used to determine similarities in meal plan purchase and use for a total of 599 roommate pairs (n=1186 students), and 557 floormates.
Results Students did not use all of the meals available to them; 7% of students did not use their meal plan for an entire month. After controlling for socioeconomic factors, compared to students on unlimited meal plans, students on the cheapest meal plan were more likely to report food insecurity (OR=2.2, 95% CI=1.2, 4.1). In Fall, 26% of students on unlimited meal plans reported food insecurity. Students on the 180 meals/semester meal plan who used fewer meals were more likely to report food insecurity (OR=0.9, 95% CI=0.8, 1.0); after gender stratification this was only evident for males. Students’ meal plan use was lower if the student worked a job (β=-1.3, 95% CI=-2.3, -0.3) and higher when their roommate used their meal plan frequently (β=0.09, 99% CI=0.04, 0.14). Roommates on the same meal plan (OR=1.56, 99% CI=1.28, 1.89) were more likely to use their meals together.
Discussion This study suggests that determining why students are not using their meal plan may be key to minimizing the prevalence of food insecurity on college campuses, and that strategic roommate assignments may result in students’ using their meal plan more frequently. Students’ meal plan information provides objective insights into students’ university transition.
Methods First-year students’ meal plan and residence information was provided by a large, public, southwestern university for the 2015-2016 academic year. A subset of students (n=619) self-reported their food security status. Logistic generalized estimating equations (GEEs) were used to determine if meal plan purchase and use were associated with food insecurity. Linear GEEs were used to examine several potential reasons for lower meal plan use. Logistic and Linear GEEs were used to determine similarities in meal plan purchase and use for a total of 599 roommate pairs (n=1186 students), and 557 floormates.
Results Students did not use all of the meals available to them; 7% of students did not use their meal plan for an entire month. After controlling for socioeconomic factors, compared to students on unlimited meal plans, students on the cheapest meal plan were more likely to report food insecurity (OR=2.2, 95% CI=1.2, 4.1). In Fall, 26% of students on unlimited meal plans reported food insecurity. Students on the 180 meals/semester meal plan who used fewer meals were more likely to report food insecurity (OR=0.9, 95% CI=0.8, 1.0); after gender stratification this was only evident for males. Students’ meal plan use was lower if the student worked a job (β=-1.3, 95% CI=-2.3, -0.3) and higher when their roommate used their meal plan frequently (β=0.09, 99% CI=0.04, 0.14). Roommates on the same meal plan (OR=1.56, 99% CI=1.28, 1.89) were more likely to use their meals together.
Discussion This study suggests that determining why students are not using their meal plan may be key to minimizing the prevalence of food insecurity on college campuses, and that strategic roommate assignments may result in students’ using their meal plan more frequently. Students’ meal plan information provides objective insights into students’ university transition.
Contributorsvan Woerden, Irene (Author) / Bruening, Meg (Thesis advisor) / Hruschka, Daniel (Committee member) / Schaefer, David (Committee member) / Vega-Lopez, Sonia (Committee member) / Adams, Marc (Committee member) / Arizona State University (Publisher)
Created2019
Description
Background: Childhood obesity is one of the most serious public health concerns in the United States and has been associated with low levels of physical activity. Schools are ideal physical activity promotion sites but school physical activity opportunities have decreased due the increased focus on academic performance. Before-school programs provide a good opportunity for children to engage in physical activity as well as improve their readiness to learn. Purpose: The purpose of this study was to examine the effect of a before-school running/walking club on children's physical activity and on-task behavior. Methods: Participants were third and fourth grade children from two schools in the Southwestern United States who participated in a before-school running/walking club that met two times each week. The study employed a two-phase experimental design with an initial baseline phase and an alternating treatments phase. Physical activity was monitored using pedometers and on-task behavior was assessed through systematic observation. Data analysis included visual analysis, descriptive statistics, as well as multilevel modeling. Results: Children accumulated substantial amounts of physical activity within the before-school program (School A: 1731 steps, 10:02 MVPA minutes; School B: 1502 steps, 8:30 MVPA minutes) and, on average, did not compensate by decreasing their physical activity during the rest of the school day. Further, on-task behavior was significantly higher on days the children attended the before-school program than on days they did not (School A=15.78%, pseudo-R2=.34 [strong effect]; School B=14.26%, pseudo-R2=.22 [moderate effect]). Discussion: Results provide evidence for the positive impact of before-school programs on children's physical activity and on-task behavior. Such programs do not take time away from academics and may be an attractive option for schools.
ContributorsStylianou, Michalis (Author) / Kulinna, Pamela H. (Thesis advisor) / Van Der Mars, Hans (Committee member) / Amazeen, Eric (Committee member) / Adams, Marc (Committee member) / Mahar, Matthew T. (Committee member) / Arizona State University (Publisher)
Created2014
Effect of a Wii Fit® intervention on balance, muscular fitness, and bone health in middle-aged women
Description
Sustaining a fall can be hazardous for those with low bone mass. Interventions exist to reduce fall-risk, but may not retain long-term interest. "Exergaming" has become popular in older adults as a therapy, but no research has been done on its preventative ability in non-clinical populations. The purpose was to determine the impact of 12-weeks of interactive play with the Wii Fit® on balance, muscular fitness, and bone health in peri- menopausal women. METHODS: 24 peri-menopausal-women were randomized into study groups. Balance was assessed using the Berg/FICSIT-4 and a force plate. Muscular strength was measured using the isokinetic dynamometer at 60°/180°/240°/sec and endurance was assessed using 50 repetitions at 240°/sec. Bone health was tracked using dual-energy x-ray absorptiometry (DXA) for the hip/lumbar spine and qualitative ultrasound (QUS) of the heel. Serum osteocalcin was assessed by enzyme immunoassay. Physical activity was quantified using the Women's Health Initiative Physical Activity Questionnaire and dietary patterns were measured using the Nurses' Health Food Frequency Questionnaire. All measures were repeated at weeks 6 and 12, except for the DXA, which was completed pre-post. RESULTS: There were no significant differences in diet and PA between groups. Wii Fit® training did not improve scores on the Berg/FICSIT-4, but improved center of pressure on the force plate for Tandem Step, Eyes Closed (p-values: 0.001-0.051). There were no significant improvements for muscular fitness at any of the angular velocities. DXA BMD of the left femoral neck improved in the intervention group (+1.15%) and decreased in the control (-1.13%), but no other sites had significant changes. Osteocalcin indicated no differences in bone turnover between groups at baseline, but the intervention group showed increased bone turnover between weeks 6 and 12. CONCLUSIONS: Findings indicate that WiiFit® training may improve balance by preserving center of pressure. QUS, DXA and osteocalcin data confirm that those in the intervention group were experiencing more bone turnover and bone formation than the control group. In summary, twelve weeks of strength /balance training with the Wii Fit® shows promise as a preventative intervention to reduce fall and fracture risk in non-clinical middle aged women who are at risk.
ContributorsWherry, Sarah Jo (Author) / Swan, Pamela D (Thesis advisor) / Adams, Marc (Committee member) / Der Ananian, Cheryl (Committee member) / Sweazea, Karen (Committee member) / Vaughan, Linda (Committee member) / Arizona State University (Publisher)
Created2014
Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
Chronic diseases are the leading causes of death in the United States. Dietary behaviors influence the risk of developing multiple chronic diseases. The U.S. population consumes too few fruits and vegetables and too much sugar sweetened beverages (SSB) and fast food. The Social Ecological Model (SEM) was created as a framework for health promotion interventions. The SEM organizes factors that can influence health into five layers: intrapersonal factors, interpersonal processes, institutional/organizational factors, community factors, and public policy. Each layer can influence dietary behaviors and other layers.
This work aims to understand how the community layer, represented by the food environment, moderates the association of two other layers and dietary behaviors: the interpersonal layer, represented by receiving health care provider’s (HCP) advice to lose weight, and the policy layer, represented by participation in the Supplemental Nutrition Assistance Program (SNAP), and a policy change within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).
Participant data were obtained from a household telephone survey of 2,211 adults in four cities in New Jersey from two cross-sectional panels in 2009-10 and 2014. Community food data were purchased and classified according to previously established protocol. Interaction and stratified analyses determined the differences in the association between HCP advice, SNAP participation, and time (for WIC participants) and eating behaviors by the food environment.
Interaction and stratified analyses revealed that HCP advice was associated with a decrease in SSB consumption when participants lived near a small grocery store, or far from a supermarket, limited service restaurant (LSR), or convenience store. SNAP participation was associated with a higher SSB consumption when respondents lived close to a small grocery store, supermarket, and LSR. There were no differences in fruit and vegetable consumption between two time points among WIC participants, or by food outlet.
The food environment, part of the community layer of SEM, moderated the relationship between the interpersonal layer and dietary behaviors and the policy layer and dietary behaviors. The association between HCP advice and dietary behaviors and SNAP participation and dietary behaviors were both influenced by the food environment in which participants lived.
This work aims to understand how the community layer, represented by the food environment, moderates the association of two other layers and dietary behaviors: the interpersonal layer, represented by receiving health care provider’s (HCP) advice to lose weight, and the policy layer, represented by participation in the Supplemental Nutrition Assistance Program (SNAP), and a policy change within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).
Participant data were obtained from a household telephone survey of 2,211 adults in four cities in New Jersey from two cross-sectional panels in 2009-10 and 2014. Community food data were purchased and classified according to previously established protocol. Interaction and stratified analyses determined the differences in the association between HCP advice, SNAP participation, and time (for WIC participants) and eating behaviors by the food environment.
Interaction and stratified analyses revealed that HCP advice was associated with a decrease in SSB consumption when participants lived near a small grocery store, or far from a supermarket, limited service restaurant (LSR), or convenience store. SNAP participation was associated with a higher SSB consumption when respondents lived close to a small grocery store, supermarket, and LSR. There were no differences in fruit and vegetable consumption between two time points among WIC participants, or by food outlet.
The food environment, part of the community layer of SEM, moderated the relationship between the interpersonal layer and dietary behaviors and the policy layer and dietary behaviors. The association between HCP advice and dietary behaviors and SNAP participation and dietary behaviors were both influenced by the food environment in which participants lived.
ContributorsLorts, Cori Elizabeth (Author) / Ohri-Vachaspati, Punam (Thesis advisor) / Adams, Marc (Committee member) / Hooker, Steven (Committee member) / Roberto, Anthony (Committee member) / Tasevska, Natasha (Committee member) / Arizona State University (Publisher)
Created2017
Description
Background: Exercise is Medicine (EIM) is a health promotion strategy for addressing physical inactivity in healthcare. However, it is unknown how to successfully implement the processes.
Purpose: The purpose of this study was to understand how implementing EIM influenced provider behaviors in a university-based healthcare system, using a process evaluation.
Methods: A multiple baseline, time series design was used. Providers were allocated to three groups. Group 1 (n=11) was exposed to an electronic medical record (EMR) systems change, EIM-related resources, and EIM training session. Group 2 (n=5) received the EMR change and resources but no training. Group 3 (n=6) was only exposed to the systems change. The study was conducted across three phases. Outcomes included asking about patient physical activity (PA) as a vital sign (PAVS), prescribing PA (ExRx), and providing PA resources or referrals. Patient surveys and EMR data were examined. Time series analysis, chi-square, and logistic regression were used.
Results: Patient survey data revealed the systems change increased patient reports of being asked about PA, χ2(4) = 95.47, p < .001 for all groups. There was a significant effect of training and resource dissemination on patients receiving PA advice, χ2(4) = 36.25, p < .001. Patients receiving PA advice was greater during phase 2 (OR = 4.7, 95% CI = 2.0-11.0) and phase 3 (OR = 2.9, 95% CI = 1.2-7.4). Increases were also observed in EMR data for PAVS, χ2(2) = 29.27, p <. 001 during implementation for all groups. Increases in PA advice χ2(2) = 140.90, p < .001 occurred among trained providers only. No statistically significant change was observed for ExRx, PA resources or PA referrals. However, visual analysis showed an upwards trend among trained providers.
Conclusions: An EMR systems change is effective for increasing the collection of the PAVS. Training and resources may influence provider behavior but training alone increased provider documentation. The low levels of documented outcomes for PA advice, ExRx, resources, or referrals may be due to the limitations of the EMR system. This approach was effective for examining the EIM Solution and scaled-up, longer trials may yield more robust results.
Purpose: The purpose of this study was to understand how implementing EIM influenced provider behaviors in a university-based healthcare system, using a process evaluation.
Methods: A multiple baseline, time series design was used. Providers were allocated to three groups. Group 1 (n=11) was exposed to an electronic medical record (EMR) systems change, EIM-related resources, and EIM training session. Group 2 (n=5) received the EMR change and resources but no training. Group 3 (n=6) was only exposed to the systems change. The study was conducted across three phases. Outcomes included asking about patient physical activity (PA) as a vital sign (PAVS), prescribing PA (ExRx), and providing PA resources or referrals. Patient surveys and EMR data were examined. Time series analysis, chi-square, and logistic regression were used.
Results: Patient survey data revealed the systems change increased patient reports of being asked about PA, χ2(4) = 95.47, p < .001 for all groups. There was a significant effect of training and resource dissemination on patients receiving PA advice, χ2(4) = 36.25, p < .001. Patients receiving PA advice was greater during phase 2 (OR = 4.7, 95% CI = 2.0-11.0) and phase 3 (OR = 2.9, 95% CI = 1.2-7.4). Increases were also observed in EMR data for PAVS, χ2(2) = 29.27, p <. 001 during implementation for all groups. Increases in PA advice χ2(2) = 140.90, p < .001 occurred among trained providers only. No statistically significant change was observed for ExRx, PA resources or PA referrals. However, visual analysis showed an upwards trend among trained providers.
Conclusions: An EMR systems change is effective for increasing the collection of the PAVS. Training and resources may influence provider behavior but training alone increased provider documentation. The low levels of documented outcomes for PA advice, ExRx, resources, or referrals may be due to the limitations of the EMR system. This approach was effective for examining the EIM Solution and scaled-up, longer trials may yield more robust results.
ContributorsBirchfield, Natasha R (Author) / Der Ananian, Cheryl (Thesis advisor) / Krasnow, Aaron (Committee member) / Doebbeling, Bradley (Committee member) / Adams, Marc (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2019