Matching Items (295)
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
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
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
Identifying disease biomarkers may aid in the early detection of breast cancer and improve patient outcomes. Recent evidence suggests that tumors are immunogenic and therefore patients may launch an autoantibody response to tumor associated antigens. Single-chain variable fragments of autoantibodies derived from regional lymph node B cells of breast cancer patients were used to discover these tumor associated biomarkers on protein microarrays. Six candidate biomarkers were discovered from 22 heavy chain-only variable region antibody fragments screened. Validation tests are necessary to confirm the tumorgenicity of these antigens. However, the use of single-chain variable autoantibody fragments presents a novel platform for diagnostics and cancer therapeutics.
ContributorsSharman, M. Camila (Author) / Magee, Dewey (Mitch) (Thesis director) / Wallstrom, Garrick (Committee member) / Petritis, Brianne (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / Virginia G. Piper Center for Personalized Diagnostics (Contributor) / Biodesign Institute (Contributor)
Created2012-12
Description
Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.
ContributorsKrajmalnik-Brown, Rosa (Author) / Lozupone, Catherine (Author) / Kang, Dae Wook (Author) / Adams, James (Author) / Biodesign Institute (Contributor)
Created2015-03-12
Description
Background
Drosophila melanogaster has been established as a model organism for investigating the developmental gene interactions. The spatio-temporal gene expression patterns of Drosophila melanogaster can be visualized by in situ hybridization and documented as digital images. Automated and efficient tools for analyzing these expression images will provide biological insights into the gene functions, interactions, and networks. To facilitate pattern recognition and comparison, many web-based resources have been created to conduct comparative analysis based on the body part keywords and the associated images. With the fast accumulation of images from high-throughput techniques, manual inspection of images will impose a serious impediment on the pace of biological discovery. It is thus imperative to design an automated system for efficient image annotation and comparison.
Results
We present a computational framework to perform anatomical keywords annotation for Drosophila gene expression images. The spatial sparse coding approach is used to represent local patches of images in comparison with the well-known bag-of-words (BoW) method. Three pooling functions including max pooling, average pooling and Sqrt (square root of mean squared statistics) pooling are employed to transform the sparse codes to image features. Based on the constructed features, we develop both an image-level scheme and a group-level scheme to tackle the key challenges in annotating Drosophila gene expression pattern images automatically. To deal with the imbalanced data distribution inherent in image annotation tasks, the undersampling method is applied together with majority vote. Results on Drosophila embryonic expression pattern images verify the efficacy of our approach.
Conclusion
In our experiment, the three pooling functions perform comparably well in feature dimension reduction. The undersampling with majority vote is shown to be effective in tackling the problem of imbalanced data. Moreover, combining sparse coding and image-level scheme leads to consistent performance improvement in keywords annotation.
Drosophila melanogaster has been established as a model organism for investigating the developmental gene interactions. The spatio-temporal gene expression patterns of Drosophila melanogaster can be visualized by in situ hybridization and documented as digital images. Automated and efficient tools for analyzing these expression images will provide biological insights into the gene functions, interactions, and networks. To facilitate pattern recognition and comparison, many web-based resources have been created to conduct comparative analysis based on the body part keywords and the associated images. With the fast accumulation of images from high-throughput techniques, manual inspection of images will impose a serious impediment on the pace of biological discovery. It is thus imperative to design an automated system for efficient image annotation and comparison.
Results
We present a computational framework to perform anatomical keywords annotation for Drosophila gene expression images. The spatial sparse coding approach is used to represent local patches of images in comparison with the well-known bag-of-words (BoW) method. Three pooling functions including max pooling, average pooling and Sqrt (square root of mean squared statistics) pooling are employed to transform the sparse codes to image features. Based on the constructed features, we develop both an image-level scheme and a group-level scheme to tackle the key challenges in annotating Drosophila gene expression pattern images automatically. To deal with the imbalanced data distribution inherent in image annotation tasks, the undersampling method is applied together with majority vote. Results on Drosophila embryonic expression pattern images verify the efficacy of our approach.
Conclusion
In our experiment, the three pooling functions perform comparably well in feature dimension reduction. The undersampling with majority vote is shown to be effective in tackling the problem of imbalanced data. Moreover, combining sparse coding and image-level scheme leads to consistent performance improvement in keywords annotation.
ContributorsSun, Qian (Author) / Muckatira, Sherin (Author) / Yuan, Lei (Author) / Ji, Shuiwang (Author) / Newfeld, Stuart (Author) / Kumar, Sudhir (Author) / Ye, Jieping (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-12-03
Description
Background
“Stoichioproteomics” relates the elemental composition of proteins and proteomes to variation in the physiological and ecological environment. To help harness and explore the wealth of hypotheses made possible under this framework, we introduce GRASP (http://www.graspdb.net), a public bioinformatic knowledgebase containing information on the frequencies of 20 amino acids and atomic composition of their side chains. GRASP integrates comparative protein composition data with annotation data from multiple public databases. Currently, GRASP includes information on proteins of 12 sequenced Drosophila (fruit fly) proteomes, which will be expanded to include increasingly diverse organisms over time. In this paper we illustrate the potential of GRASP for testing stoichioproteomic hypotheses by conducting an exploratory investigation into the composition of 12 Drosophila proteomes, testing the prediction that protein atomic content is associated with species ecology and with protein expression levels.
Results
Elements varied predictably along multivariate axes. Species were broadly similar, with the D. willistoni proteome a clear outlier. As expected, individual protein atomic content within proteomes was influenced by protein function and amino acid biochemistry. Evolution in elemental composition across the phylogeny followed less predictable patterns, but was associated with broad ecological variation in diet. Using expression data available for D. melanogaster, we found evidence consistent with selection for efficient usage of elements within the proteome: as expected, nitrogen content was reduced in highly expressed proteins in most tissues, most strongly in the gut, where nutrients are assimilated, and least strongly in the germline.
Conclusions
The patterns identified here using GRASP provide a foundation on which to base future research into the evolution of atomic composition in Drosophila and other taxa.
“Stoichioproteomics” relates the elemental composition of proteins and proteomes to variation in the physiological and ecological environment. To help harness and explore the wealth of hypotheses made possible under this framework, we introduce GRASP (http://www.graspdb.net), a public bioinformatic knowledgebase containing information on the frequencies of 20 amino acids and atomic composition of their side chains. GRASP integrates comparative protein composition data with annotation data from multiple public databases. Currently, GRASP includes information on proteins of 12 sequenced Drosophila (fruit fly) proteomes, which will be expanded to include increasingly diverse organisms over time. In this paper we illustrate the potential of GRASP for testing stoichioproteomic hypotheses by conducting an exploratory investigation into the composition of 12 Drosophila proteomes, testing the prediction that protein atomic content is associated with species ecology and with protein expression levels.
Results
Elements varied predictably along multivariate axes. Species were broadly similar, with the D. willistoni proteome a clear outlier. As expected, individual protein atomic content within proteomes was influenced by protein function and amino acid biochemistry. Evolution in elemental composition across the phylogeny followed less predictable patterns, but was associated with broad ecological variation in diet. Using expression data available for D. melanogaster, we found evidence consistent with selection for efficient usage of elements within the proteome: as expected, nitrogen content was reduced in highly expressed proteins in most tissues, most strongly in the gut, where nutrients are assimilated, and least strongly in the germline.
Conclusions
The patterns identified here using GRASP provide a foundation on which to base future research into the evolution of atomic composition in Drosophila and other taxa.
ContributorsGilbert, James D. J. (Author) / Acquisti, Claudia (Author) / Martinson, Holly M. (Author) / Elser, James (Author) / Kumar, Sudhir (Author) / Fagan, William F. (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2013-09-04
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