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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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Consideration of both biological and human-use dynamics in coupled social-ecological systems is essential for the success of interventions such as marine reserves. As purely human institutions, marine reserves have no direct effects on ecological systems. Consequently, the success of a marine reserve depends on managers` ability to alter human behavior

Consideration of both biological and human-use dynamics in coupled social-ecological systems is essential for the success of interventions such as marine reserves. As purely human institutions, marine reserves have no direct effects on ecological systems. Consequently, the success of a marine reserve depends on managers` ability to alter human behavior in the direction and magnitude that supports reserve objectives. Further, a marine reserve is just one component in a larger coupled social-ecological system. The social, economic, political, and biological landscape all determine the social acceptability of a reserve, conflicts that arise, how the reserve interacts with existing fisheries management, accuracy of reserve monitoring, and whether the reserve is ultimately able to meet conservation and fishery enhancement goals. Just as the social-ecological landscape is critical at all stages for marine reserve, from initial establishment to maintenance, the reserve in turn interacts with biological and human use dynamics beyond its borders. Those interactions can lead to the failure of a reserve to meet management goals, or compromise management goals outside the reserve. I use a bio-economic model of a fishery in a spatially patchy environment to demonstrate how the pre-reserve fisheries management strategy determines the pattern of fishing effort displacement once the reserve is established, and discuss the social, political, and biological consequences of different patterns for the reserve and the fishery. Using a stochastic bio-economic model, I demonstrate how biological and human use connectivity can confound the accurate detection of reserve effects by violating assumptions in the quasi-experimental framework. Finally, I examine data on recreational fishing site selection to investigate changes in response to the announcement of enforcement of a marine reserve in the Gulf of California, Mexico. I generate a scale of fines that would fully or partially protect the reserve, providing a data-driven way for managers to balance biological and socio-economic goals. I suggest that natural resource managers consider human use dynamics with the same frequency, rigor, and tools as they do biological stocks.
ContributorsFujitani, Marie (Author) / Abbott, Joshua (Thesis advisor) / Fenichel, Eli (Thesis advisor) / Gerber, Leah (Committee member) / Anderies, John (Committee member) / Arizona State University (Publisher)
Created2014
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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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DescriptionThis paper provides an analysis of the differences in impacts made by companies that promote their sustainability efforts. A comparison of companies reveals that the ones with greater supply chain influence and larger consumer bases can make more concrete progress in terms of accomplishment for the sustainability realm.
ContributorsBeaubien, Courtney Lynn (Author) / Anderies, John (Thesis director) / Allenby, Brad (Committee member) / Janssen, Marco (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
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In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that

In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that are more specific to the archaeological cases: i) societal choices are influenced by robustness–vulnerability trade-offs, ii) there is interplay between robustness–vulnerability trade-offs and robustness–performance trade-offs, iii) societies often get locked in to particular strategies, and iv) multiple positive feedbacks escalate the perceived cost of societal change. We then discuss whether these lock-in traps can be prevented or whether the risks associated with them can be mitigated. We conclude by highlighting how these long-term historical studies can help us to understand current society, societal practices, and the nexus between ecology and society.

ContributorsSchoon, Michael (Author) / Fabricius, Christo (Author) / Anderies, John (Author) / Nelson, Margaret (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011
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What relationships can be understood between resilience and vulnerability in social-ecological systems? In particular, what vulnerabilities are exacerbated or ameliorated by different sets of social practices associated with water management? These questions have been examined primarily through the study of contemporary or recent historic cases. Archaeology extends scientific observation beyond

What relationships can be understood between resilience and vulnerability in social-ecological systems? In particular, what vulnerabilities are exacerbated or ameliorated by different sets of social practices associated with water management? These questions have been examined primarily through the study of contemporary or recent historic cases. Archaeology extends scientific observation beyond all social memory and can thus illuminate interactions occurring over centuries or millennia. We examined trade-offs of resilience and vulnerability in the changing social, technological, and environmental contexts of three long-term, pre-Hispanic sequences in the U.S. Southwest: the Mimbres area in southwestern New Mexico (AD 650–1450), the Zuni area in northern New Mexico (AD 850–1540), and the Hohokam area in central Arizona (AD 700–1450). In all three arid landscapes, people relied on agricultural systems that depended on physical and social infrastructure that diverted adequate water to agricultural soils. However, investments in infrastructure varied across the cases, as did local environmental conditions. Zuni farming employed a variety of small-scale water control strategies, including centuries of reliance on small runoff agricultural systems; Mimbres fields were primarily watered by small-scale canals feeding floodplain fields; and the Hohokam area had the largest canal system in pre-Hispanic North America. The cases also vary in their historical trajectories: at Zuni, population and resource use remained comparatively stable over centuries, extending into the historic period; in the Mimbres and Hohokam areas, there were major demographic and environmental transformations. Comparisons across these cases thus allow an understanding of factors that promote vulnerability and influence resilience in specific contexts.

ContributorsNelson, Margaret (Author) / Kintigh, Keith (Author) / Abbott, David (Author) / Anderies, John (Author) / College of Liberal Arts and Sciences (Contributor)
Created2010
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Perceptions of climate variability and change reflect local concerns and the actual impacts of climate phenomena on people's lives. Perceptions are the bases of people's decisions to act, and they determine what adaptive measures will be taken. But perceptions of climate may not always be aligned with scientific observations because

Perceptions of climate variability and change reflect local concerns and the actual impacts of climate phenomena on people's lives. Perceptions are the bases of people's decisions to act, and they determine what adaptive measures will be taken. But perceptions of climate may not always be aligned with scientific observations because they are influenced by socio-economic and ecological variables. To find sustainability solutions to climate-change challenges, researchers and policy makers need to understand people's perceptions so that they can account for likely responses. Being able to anticipate responses will increase decision-makers' capacities to create policies that support effective adaptation strategies. I analyzed Mexican maize farmers' perceptions of drought variability as a proxy for their perceptions of climate variability and change. I identified the factors that contribute to the perception of changing drought frequency among farmers in the states of Chiapas, Mexico, and Sinaloa. I conducted Chi-square tests and Logit regression analyses using data from a survey of 1092 maize-producing households in the three states. Results showed that indigenous identity, receipt of credits or loans, and maize-type planted were the variables that most strongly influenced perceptions of drought frequency. The results suggest that climate-adaptation policy will need to consider the social and institutional contexts of farmers' decision-making, as well as the agronomic options for smallholders in each state.
ContributorsRodríguez, Natalia (Author) / Eakin, Hallie (Thesis advisor) / Muneepeerakul, Rachata (Thesis advisor) / Manuel-Navarrete, David (Committee member) / Arizona State University (Publisher)
Created2015
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Description

An understanding of the formation of spatial heterogeneity is important because spatial heterogeneity leads to functional consequences at the ecosystem scale; however, such an understanding is still limited. Particularly, research simultaneously considering both external variables and internal feedbacks (self-organization) is rare, partly because these two drivers are addressed under different

An understanding of the formation of spatial heterogeneity is important because spatial heterogeneity leads to functional consequences at the ecosystem scale; however, such an understanding is still limited. Particularly, research simultaneously considering both external variables and internal feedbacks (self-organization) is rare, partly because these two drivers are addressed under different methodological frameworks. In this dissertation, I show the prevalence of internal feedbacks and their interaction with heterogeneity in the preexisting template to form spatial pattern. I use a variety of techniques to account for both the top-down template effect and bottom-up self-organization. Spatial patterns of nutrients in stream surface water are influenced by the self-organized patch configuration originating from the internal feedbacks between nutrient concentration, biological patchiness, and the geomorphic template. Clumps of in-stream macrophyte are shaped by the spatial gradient of water permanence and local self-organization. Additionally, significant biological interactions among plant species also influence macrophyte distribution. The relative contributions of these drivers change in time, responding to the larger external environments or internal processes of ecosystem development. Hydrologic regime alters the effect of geomorphic template and self-organization on in-stream macrophyte distribution. The relative importance of niche vs. neutral processes in shaping biodiversity pattern is a function of hydrology: neutral processes are more important in either very high or very low discharge periods. For the spatial pattern of nutrients, as the ecosystem moves toward late succession and nitrogen becomes more limiting, the effect of self-organization intensifies. Changes in relative importance of different drivers directly affect ecosystem macroscopic properties, such as ecosystem resilience. Stronger internal feedbacks in average to wetter years are shown to increase ecosystem resistance to elevated external stress, and make the backward shifts (vegetation loss) much more gradual. But it causes increases in ecosystem hysteresis effect. Finally, I address the question whether functional consequences of spatial heterogeneity feed back to influence the processes from which spatial heterogeneity emerged through a conceptual review. Such feedbacks are not likely. Self-organized spatial patterning is a result of regular biological processes of organisms. Individual organisms do not benefit from such order. It is order for free, and for nothing.

ContributorsDong, Xiaolin (Author) / Grimm, Nancy (Thesis advisor) / Muneepeerakul, Rachata (Thesis advisor) / Franklin, Janet (Committee member) / Heffernan, James B (Committee member) / Sabo, John (Committee member) / Arizona State University (Publisher)
Created2015
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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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Social-ecological systems (SES) are replete with hard and soft human-made components (or infrastructures) that are consciously-designed to perform specific functions valued by humans. How these infrastructures mediate human-environment interactions is thus a key determinant of many sustainability problems in present-day SES. This dissertation examines the question of how some of

Social-ecological systems (SES) are replete with hard and soft human-made components (or infrastructures) that are consciously-designed to perform specific functions valued by humans. How these infrastructures mediate human-environment interactions is thus a key determinant of many sustainability problems in present-day SES. This dissertation examines the question of how some of the designed aspects of physical and social infrastructures influence the robustness of SES under global change. Due to the fragility of rural livelihood systems, locally-managed common-pool resource systems that depend on infrastructure, such as irrigated agriculture and community forestry, are of particular importance to address this sustainability question. This dissertation presents three studies that explored the robustness of communal irrigation and forestry systems to economic or environmental shocks. The first study examined how the design of irrigation infrastructure affects the robustness of system performance to an economic shock. Using a stylized dynamic model of an irrigation system as a testing ground, this study shows that changes in infrastructure design can induce fundamental changes in qualitative system behavior (i.e., regime shifts) as well as altered robustness characteristics. The second study explored how connectedness among social units (a kind of social infrastructure) influenced the post-failure transformations of large-N forest commons under economic globalization. Using inferential statistics, the second study argues that some attributes of the social connectedness that helped system robustness in the past made the system more vulnerable to undesirable transformations in the current era. The third study explored the question of how to guide adaptive management of SES for more robustness under uncertainty. This study used an existing laboratory behavioral experiment in which human-subjects tackle a decision problem on collective management of an irrigation system under environmental uncertainty. The contents of group communication and the decisions of individuals were analyzed to understand how configurations of learning-by-doing and other adaptability-related conditions may be causally linked to robustness under environmental uncertainty. The results show that robust systems are characterized by two conditions: active learning-by-doing through outer-loop processes, i.e., frequent updating of shared assumptions or goals that underlie specific group strategies, and frequent monitoring and reflection of past outcomes.
ContributorsYu, Jae Hoon David (Author) / Anderies, John M. (Thesis advisor) / Janssen, Marco A. (Committee member) / Muneepeerakul, Rachata (Committee member) / Arizona State University (Publisher)
Created2015