Matching Items (46)
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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

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
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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

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
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Description
Thirty six percent of Americans are obese and thirty three percent are overweight; obesity has become a known killer in the U.S. yet its prevalence has maintained a firm grasp on the U.S. population and continues to spread across the globe as other countries slowly adopt the American lifestyle. A

Thirty six percent of Americans are obese and thirty three percent are overweight; obesity has become a known killer in the U.S. yet its prevalence has maintained a firm grasp on the U.S. population and continues to spread across the globe as other countries slowly adopt the American lifestyle. A survey was compiled collecting demographic and body mass index (BMI) information, as well as Tanofsky-Kraff’s (2009) “Assess Eating in the Absence of Hunger” survey questions. The survey used for this study was emailed out to Arizona State University students in Barrett, The Honors College, and the ASU School of Nutrition and Health Promotion listservs. A total of 457 participants completed the survey, 72 males and 385 females (mean age, 24.5±7.7 y; average body mass index (BMI), 23.4 ± 4.8 [a BMI of 25-29.9 is classified as overweight]). When comparing BMI with the living situation, 71% of obese students were living at home with family versus off campus with friends or alone. For comparison, 45% of normal weight students lived at home with family.  These data could help structure prevention plans targeting college students by focusing on weight gain prevention at the family level. Results from the Tanofsky-Kraff (2009) survey revealed there was not a significant relationship between external or physical cues and BMI in men or women, but there was a significant positive correlation between emotional cues and BMI in women only. Anger and sadness were the emotional cues in women related to initiating consumption past satiation and consumption following several hours of fasting. Although BMI was inversely related to physical activity in this sample (r = -0.132; p=0.005), controlling for physical activity did not impact the significant associations of BMI with anger or sadness (P>0.05).  This information is important in targeting prevention programs to address behavioral change and cognitive awareness of the effects of emotion on over-consumption.
ContributorsGarza, Andrea Marie (Author) / Johnston, Carol (Thesis director) / Jacobs, Mark (Committee member) / Coletta, Dawn (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
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New-onset diabetes after kidney transplantation (NODAT) occurs in 20% of kidney transplant patients. In 5 patients who are at risk for new-onset diabetes after kidney transplantation, skeletal muscle gene expression profiling was performed both before and after kidney transplant. The differences in gene expression before and after transplant were compared

New-onset diabetes after kidney transplantation (NODAT) occurs in 20% of kidney transplant patients. In 5 patients who are at risk for new-onset diabetes after kidney transplantation, skeletal muscle gene expression profiling was performed both before and after kidney transplant. The differences in gene expression before and after transplant were compared in order to identify specific genes that could be linked to developing NODAT. These findings could open new avenues for future research.
ContributorsLowery, Clint Curtis (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Willis, Wayne (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
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DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body.

DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body. By using research data from a preliminary study of lean and obese clinical subjects, this study attempts to put together a profile of the differences in DNA methylation that can be observed between two particular body tissues from this subject group: blood and skeletal muscle. This study allows us to start describing the changes that occur at the epigenetic level that influence how differently these two tissues operate, along with seeing how these tissues change between individuals of different weight classes, especially in the context of the development of symptoms of Type 2 Diabetes.
ContributorsRappazzo, Micah Gabriel (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Dinu, Valentin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
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Obesity and related health disparities including type 2 diabetes disproportionately impact Latino youth. These health disparities may be the result of gene-environment interactions, but limited research has examined these interactions in the pediatric age group. Lifestyle intervention is the cornerstone for preventing diabetes among high-risk populations and epigenetic and genetic

Obesity and related health disparities including type 2 diabetes disproportionately impact Latino youth. These health disparities may be the result of gene-environment interactions, but limited research has examined these interactions in the pediatric age group. Lifestyle intervention is the cornerstone for preventing diabetes among high-risk populations and epigenetic and genetic factors may help explain the biological mechanisms underlying diabetes risk reduction following lifestyle changes. MicroRNAs (miRNAs) are small, non-coding RNA’s that regulate gene expression and have emerged as potential biomarkers for predicting type 2 diabetes risk in adults but have yet to be applied to youth. Therefore, the purpose of this study was to identify changes in miRNA expression among Latino youth with prediabetes (4 female/2 male, ages 14-16, BMI percentile 99 ±.2) who participated in a 12-week lifestyle intervention focused on increasing physical activity and improving nutrition-related behaviors.
ContributorsKarch, Jamie (Co-author) / Day, Samantha (Co-author) / Shaibi, Gabriel (Thesis director) / Coletta, Dawn (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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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

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.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
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Energy use within urban building stocks is continuing to increase globally as populations expand and access to electricity improves. This projected increase in demand could require deployment of new generation capacity, but there is potential to offset some of this demand through modification of the buildings themselves. Building

Energy use within urban building stocks is continuing to increase globally as populations expand and access to electricity improves. This projected increase in demand could require deployment of new generation capacity, but there is potential to offset some of this demand through modification of the buildings themselves. Building stocks are quasi-permanent infrastructures which have enduring influence on urban energy consumption, and research is needed to understand: 1) how development patterns constrain energy use decisions and 2) how cities can achieve energy and environmental goals given the constraints of the stock. This requires a thorough evaluation of both the growth of the stock and as well as the spatial distribution of use throughout the city. In this dissertation, a case study in Los Angeles County, California (LAC) is used to quantify urban growth, forecast future energy use under climate change, and to make recommendations for mitigating energy consumption increases. A reproducible methodological framework is included for application to other urban areas.

In LAC, residential electricity demand could increase as much as 55-68% between 2020 and 2060, and building technology lock-in has constricted the options for mitigating energy demand, as major changes to the building stock itself are not possible, as only a small portion of the stock is turned over every year. Aggressive and timely efficiency upgrades to residential appliances and building thermal shells can significantly offset the projected increases, potentially avoiding installation of new generation capacity, but regulations on new construction will likely be ineffectual due to the long residence time of the stock (60+ years and increasing). These findings can be extrapolated to other U.S. cities where the majority of urban expansion has already occurred, such as the older cities on the eastern coast. U.S. population is projected to increase 40% by 2060, with growth occurring in the warmer southern and western regions. In these growing cities, improving new construction buildings can help offset electricity demand increases before the city reaches the lock-in phase.
ContributorsReyna, Janet Lorel (Author) / Chester, Mikhail V (Thesis advisor) / Gurney, Kevin (Committee member) / Reddy, T. Agami (Committee member) / Rey, Sergio (Committee member) / Arizona State University (Publisher)
Created2016
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Description

A globally integrated carbon observation and analysis system is needed to improve the fundamental understanding of the global carbon cycle, to improve our ability to project future changes, and to verify the effectiveness of policies aiming to reduce greenhouse gas emissions and increase carbon sequestration. Building an integrated carbon observation

A globally integrated carbon observation and analysis system is needed to improve the fundamental understanding of the global carbon cycle, to improve our ability to project future changes, and to verify the effectiveness of policies aiming to reduce greenhouse gas emissions and increase carbon sequestration. Building an integrated carbon observation system requires transformational advances from the existing sparse, exploratory framework towards a dense, robust, and sustained system in all components: anthropogenic emissions, the atmosphere, the ocean, and the terrestrial biosphere. The paper is addressed to scientists, policymakers, and funding agencies who need to have a global picture of the current state of the (diverse) carbon observations.

We identify the current state of carbon observations, and the needs and notional requirements for a global integrated carbon observation system that can be built in the next decade. A key conclusion is the substantial expansion of the ground-based observation networks required to reach the high spatial resolution for CO2 and CH4 fluxes, and for carbon stocks for addressing policy-relevant objectives, and attributing flux changes to underlying processes in each region. In order to establish flux and stock diagnostics over areas such as the southern oceans, tropical forests, and the Arctic, in situ observations will have to be complemented with remote-sensing measurements. Remote sensing offers the advantage of dense spatial coverage and frequent revisit. A key challenge is to bring remote-sensing measurements to a level of long-term consistency and accuracy so that they can be efficiently combined in models to reduce uncertainties, in synergy with ground-based data.

Bringing tight observational constraints on fossil fuel and land use change emissions will be the biggest challenge for deployment of a policy-relevant integrated carbon observation system. This will require in situ and remotely sensed data at much higher resolution and density than currently achieved for natural fluxes, although over a small land area (cities, industrial sites, power plants), as well as the inclusion of fossil fuel CO2 proxy measurements such as radiocarbon in CO2 and carbon-fuel combustion tracers. Additionally, a policy-relevant carbon monitoring system should also provide mechanisms for reconciling regional top-down (atmosphere-based) and bottom-up (surface-based) flux estimates across the range of spatial and temporal scales relevant to mitigation policies. In addition, uncertainties for each observation data-stream should be assessed. The success of the system will rely on long-term commitments to monitoring, on improved international collaboration to fill gaps in the current observations, on sustained efforts to improve access to the different data streams and make databases interoperable, and on the calibration of each component of the system to agreed-upon international scales.

ContributorsCiais, P. (Author) / Dolman, A. J. (Author) / Bombelli, A. (Author) / Duren, R. (Author) / Peregon, A. (Author) / Rayner, P. J. (Author) / Miller, C. (Author) / Gobron, N. (Author) / Kinderman, G. (Author) / Marland, G. (Author) / Gruber, N. (Author) / Chevallier, F. (Author) / Andres, R. J. (Author) / Balsamo, G. (Author) / Bopp, L. (Author) / Breon, F. -M. (Author) / Broquet, G. (Author) / Dargaville, R. (Author) / Battin, T. J. (Author) / Borges, A. (Author) / Bovensmann, H. (Author) / Buchwitz, M. (Author) / Butler, J. (Author) / Canadell, J. G. (Author) / Cook, R. B. (Author) / DeFries, R. (Author) / Engelen, R. (Author) / Gurney, Kevin (Author) / Heinze, C. (Author) / Heimann, M. (Author) / Held, A. (Author) / Henry, M. (Author) / Law, B. (Author) / Luyssaert, S. (Author) / Miller, J. (Author) / Moriyama, T. (Author) / Moulin, C. (Author) / Myneni, R. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-11-30
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Errors in the specification or utilization of fossil fuel CO2 emissions within carbon budget or atmospheric CO2 inverse studies can alias the estimation of biospheric and oceanic carbon exchange. A key component in the simulation of CO2 concentrations arising from fossil fuel emissions is the spatial distribution of the emission

Errors in the specification or utilization of fossil fuel CO2 emissions within carbon budget or atmospheric CO2 inverse studies can alias the estimation of biospheric and oceanic carbon exchange. A key component in the simulation of CO2 concentrations arising from fossil fuel emissions is the spatial distribution of the emission near coastlines. Regridding of fossil fuel CO2 emissions (FFCO2) from fine to coarse grids to enable atmospheric transport simulations can give rise to mismatches between the emissions and simulated atmospheric dynamics which differ over land or water. For example, emissions originally emanating from the land are emitted from a grid cell for which the vertical mixing reflects the roughness and/or surface energy exchange of an ocean surface. We test this potential "dynamical inconsistency" by examining simulated global atmospheric CO2 concentration driven by two different approaches to regridding fossil fuel CO2 emissions. The two approaches are as follows: (1) a commonly used method that allocates emissions to grid cells with no attempt to ensure dynamical consistency with atmospheric transport and (2) an improved method that reallocates emissions to grid cells to ensure dynamically consistent results. Results show large spatial and temporal differences in the simulated CO2 concentration when comparing these two approaches. The emissions difference ranges from −30.3 TgC grid cell-1 yr-1 (−3.39 kgC m-2 yr-1) to +30.0 TgC grid cell-1 yr-1 (+2.6 kgC m-2 yr-1) along coastal margins. Maximum simulated annual mean CO2 concentration differences at the surface exceed ±6 ppm at various locations and times. Examination of the current CO2 monitoring locations during the local afternoon, consistent with inversion modeling system sampling and measurement protocols, finds maximum hourly differences at 38 stations exceed ±0.10 ppm with individual station differences exceeding −32 ppm. The differences implied by not accounting for this dynamical consistency problem are largest at monitoring sites proximal to large coastal urban areas and point sources. These results suggest that studies comparing simulated to observed atmospheric CO2 concentration, such as atmospheric CO2 inversions, must take measures to correct for this potential problem and ensure flux and dynamical consistency.

ContributorsZhang, X. (Author) / Gurney, Kevin (Author) / Rayner, P. (Author) / Liu, Y. (Author) / Asefi-Najafabady, Salvi (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-11-30