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Description
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
Description
Free coenzyme A (CoASH) carries acyl groups for the tricarboxylic acid (TCA) cycle and fatty acid metabolism, and donates acyl groups for protein posttranslational modifications. Cellular de novo CoASH synthesis starts with a pantothenate kinase (PANK1-3) phosphorylating pantothenate (vitamin B5). Mutations in PANK2 cause a subtype of neurodegeneration with brain iron accumulation (NBIA). The PANKs have differential subcellular distribution and regulatory properties. However, the purpose of each PANK has remained obscure, with knockout mouse models presenting with mild phenotypes unless challenged with a high-fat diet. Based on PANK2’s known activation by palmitoylcarnitine, the PANK2-deficient cells were challenged with palmitic acid (PAL) added to glucose-containing media. The high nutrient mixture generated a surprising “starvation” profile of reduced proliferation, low ATP, AMPK activation, and autophagy upregulation in PANK2-deficient PAL-challenged cells. Further experiments showed that fatty acids accumulated and that PANK2-deficient cells had reduced respiration when provided with palmitoylcarnitine as a substrate, seemingly due to an impaired ability to oxidize fatty acids during PAL-induced Randle Cycle activation. Intriguingly, whole-cell CoASH levels remained stable despite the PAL-induced starvation phenotype, and increasing CoASH via PANK1β overexpression did not rescue the phenotype, demonstrating a unique role for PANK2 in fatty acid metabolism. Even though a direct CoASH deficiency was not detected, there were changes in short chain CoA-derivatives, including acetyl-CoA, succinyl-CoA, and butyryl-CoA, as well as evidence of impaired TCA cycle function. These impairments in both the TCA cycle and fatty acid oxidation implicate a role for PANK2 in regulating mitochondria CoA dynamics.
ContributorsNordlie, Sandra Maria (Author) / Kruer, Michael C (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Padilla Lopez, Sergio (Committee member) / Katsanos, Christos (Committee member) / Arizona State University (Publisher)
Created2022
Description
This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA and, thus, slow the rapid increase in sedentary lifestyles. Transcranial direct current stimulation (tDCS) involves brain neuromodulation by facilitating or inhibiting spontaneous neural activity. tDCS applied to the dorsolateral prefrontal cortex (DLPFC) increases dopamine release in the striatum, an area of the brain involved in the reward–motivation pathways. I propose that a repeated intervention, consisting of tDCS applied to the DLPFC followed by a short walking exercise stimulus, enhances motivation for PA and daily PA levels in healthy adults. Results showed that using tDCS followed by short-duration walking exercise may enhance daily PA levels in low-physically active participants but may not have similar effects on those with higher levels of daily PA. Moreover, there was a significant effect on increasing intrinsic motivation for PA in males, but there were no sex-related differences in PA. These effects were not observed during a 2-week follow-up period of the study after the intervention was discontinued. Further research is needed to confirm and continue exploring the effects of tDCS on motivation for PA in larger cohorts of sedentary populations. This novel research will lead to a cascade of new evidence-based technological applications that increase PA by employing approaches rooted in biology.
ContributorsRuiz Tejada, Anaissa (Author) / Katsanos, Christos (Thesis advisor) / Neisewander, Janet (Committee member) / Sadleir, Rosalind (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2023
Description
Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function, and by inhibiting or activating LPL, respectively. Therefore, these proteins play key role in plasma lipid metabolism, but their role in regulating LPL activity in human insulin resistant (IR) (i.e., pre-diabetic) state is not known. Thus, the purpose of this research was to evaluate the concentrations of ApoC3 and ApoC2 in plasma along with the endothelial-bound LPL availability and activity in IR humans and in healthy, insulin sensitive (IS)/control humans. Insulin resistance was evaluated from plasma insulin and glucose responses to an oral glucose tolerance test, and by calculating the Matsuda index. Subjects were placed in the following groups: IR subjects, Matsuda index <4.0 (N=7; 4 males, 3 females); IS, Matsuda index >7.0 (N=11, 9 males, 2 females). IR and IS subjects received an intravenous infusion of insulin (1 mU/kg/min and 0.5 mU/kg/min, respectively) for 30 minutes to stimulate LPL activity. Whole-body endothelial-bound LPL was released from the vasculature by intravenous infusion of heparin. Plasma samples were collected 10 minutes after heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations. Although plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P = 0.02), plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03). However, ApoC2 concentration was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). These findings suggest that circulating APOC3 and ApoC2 are not key determinants regulating LPL activity during hyperinsulinemia in the vasculature of insulin resistant humans.
ContributorsJohnsson, Kailin Alexis (Author) / Katsanos, Christos (Thesis advisor) / Herman, Richard (Committee member) / De Filippis, Elena (Eleanna) (Committee member) / Arizona State University (Publisher)
Created2023
Description
In adults, consuming a high-fat meal can induce endothelial dysfunction while exercise may mitigate postprandial endothelial dysfunction. Whether exercise is protective against postprandial endothelial dysfunction in obese youth is unknown. The purpose of this study was to determine if high-intensity interval exercise (HIIE) performed the evening prior to a high-fat meal protects against postprandial endothelial dysfunction in obese adolescent males. Fourteen obese adolescent males (BMI%tile=98.5±0.6; 14.3±1.0yrs) completed the study. After initial screening, participants arrived, fasted at 9:00 in the morning where brachial artery flow-mediated dilation (FMD) was measured using duplex ultrasound after 20min of supine rest (7.0±3.0%) and completed a maximal exercise test on a cycle ergometer (VO2peak=2.6±0.5 L/min). Participants were randomized and completed 2 conditions: a morning high-fat meal challenge with evening prior HIIE (EX+M) or a morning high-fat meal challenge without prior exercise (MO). The EX+M condition included a single HIIE session on a cycle ergometer (8 X 2min at ≥90%HRmax, with 2min active recovery between bouts, 42min total) which was performed at 17:00 the evening prior to the meal challenge. In both conditions, a mixed-meal was tailored to participants body weight consisting of 0.7g of fat/kg of body weight consumed (889±95kcal; 65% Fat, 30% CHO). FMD was measured at fasting (>10hrs) and subsequently measured at 2hr and 4hr after high-fat meal consumption. Exercise did not improve fasting FMD (7.5±3.0 vs. 7.4±2.8%, P=0.927; EX+M and MO, respectively). Despite consuming a high-fat meal, FMD was not reduced at 2hr (8.4±3.4 vs. 7.6±3.9%; EX+M and MO, respectively) or 4hr (8.8±3.9 vs. 8.6±4.0%; EX+M and MO, respectively) in either condition and no differences were observed between condition (p(condition*time)=0.928). These observations remained after adjusting for baseline artery diameter and shear rate. We observed that HIIE, the evening prior, had no effect on fasting or postprandial endothelial function when compared with a meal only condition. Future research should examine whether exercise training may be able to improve postprandial endothelial function rather than a single acute bout in obese youth.
ContributorsRyder, Justin Ross (Author) / Shaibi, Gabriel Q (Thesis advisor) / Gaesser, Glenn A (Committee member) / Vega-Lopez, Sonia (Committee member) / Crespo, Noe C (Committee member) / Katsanos, Christos (Committee member) / Arizona State University (Publisher)
Created2014
Description
Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while other are nested between the myofibrils (i.e., intermyofibrillar (IMF) mitochondria). Functional and proteome differences specific to SS versus IMF mitochondria in obese individuals may contribute to reduced capacity for muscle ATP production seen in obesity. The overall goals of this work were to (1) isolate functional muscle SS and IMF mitochondria from lean and obese individuals, (2) assess enzyme activities associated with the electron transport chain and ATP production, (3) determine if elevated plasma amino acids enhance SS and IMF mitochondrial respiration and ATP production rates in SM of obese humans, and (4) determine differences in mitochondrial proteome regulating energy metabolism and key biological processes associated with SS and IMF mitochondria between lean and obese humans.
Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.
Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.
Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
ContributorsKras, Katon Anthony (Author) / Katsanos, Christos (Thesis advisor) / Chandler, Douglas (Committee member) / Dinu, Valentin (Committee member) / Mor, Tsafrir S. (Committee member) / Arizona State University (Publisher)
Created2017
Description
The Energiewende aims to drastically reduce Germany’s greenhouse gas emissions, without relying on nuclear power, while maintaining a secure and affordable energy supply. Since 2000 the country’s renewable-energy share has increased exponentially, accounting in 2017 for over a third of Germany's gross electricity consumption. This unprecedented achievement is the result of policies, tools, and institutional arrangements intended to steer society to a low-carbon economy. Despite its resounding success in renewable-energy deployment, the Energiewende is not on track to meet its decarbonization goals. Energiewende rules and regulations have generated numerous undesired consequences, and have cost much more than anticipated, a burden borne primarily by energy consumers. Why has the Energiewende not only made energy more expensive, but also failed to bring Germany closer to its decarbonization goals? I analyzed the Energiewende as a complex socio-technical system, examining its legal framework and analyzing the consequences of successive regulations; identifying major political and energy players and the factors that motivated them to pursue socio-technical change; and documenting the political trends and events in which the Energiewende is rooted and which continue to shape it. I analyzed the dynamics and the loopholes that created barriers to transition, pushed the utility sector to the brink of dissolution, and led to such undesirable outcomes as negative wholesale prices and forced exports of electricity to Germany’s European neighbors. Thirty high-level energy experts and stakeholders were interviewed to find out how the best-informed members of German society perceive the Energiewende. Surprisingly, although they were highly critical of the way the transition has unfolded, most were convinced that the transition would eventually succeed. But their definitions of success did not always depend on achieving carbon-mitigation targets. Indeed, Germany jeopardizes the achievement of these targets by changing too many policy and institutional variables at too fast a pace. Good intentions and commitment are not enough to create economies based on intermittent energy sources: they will also require intensive grid expansion and breakthroughs in storage technology. The Energiewende demonstrates starkly that collective action driven by robust political consensus is not sufficient for steering complex socio-technical systems in desired directions.
ContributorsSturm, Christine (Author) / Sarewitz, Daniel (Thesis advisor) / Miller, Clark (Committee member) / Anderies, John (Committee member) / Hirt, Paul (Committee member) / Arizona State University (Publisher)
Created2018
Description
Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying insulin resistance, (2) to determine if these changes in methylation can be altered through weight-loss induced by bariatric surgery, and (3) to identify DNA methylation biomarkers in whole blood that can be used as a surrogate for skeletal muscle.
Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.
These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.
These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
ContributorsDay, Samantha Elaine (Author) / Coletta, Dawn K. (Thesis advisor) / Katsanos, Christos (Committee member) / Mandarino, Lawrence J. (Committee member) / Shaibi, Gabriel Q. (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2017
Description
Obesity is one of the most challenging health conditions of our time, characterized by complex interactions between behavioral, environmental, and genetic factors. These interactions lead to a distinctive obese phenotype. Twenty years ago, the gut microbiota (GM) was postulated as a significant factor contributing to the obese phenotype and associated metabolic disturbances. Exercise had shown to improve and revert the metabolic abnormalities in obese individuals. Also, genistein has a suggested potential anti-obesogenic effect. Studying the dynamic interaction of the GM with relevant organs in metabolic homeostasis is crucial for the design of new long-term therapies to treat obesity. The purpose of this experimental study is to examine exercise (Exe), genistein (Gen), and their combined intervention (Exe + Gen) effects on GM composition and musculoskeletal mitochondrial oxidative function in diet-induced obese mice. Also, this study aims to explore the association between gut microbial diversity and mitochondrial oxidative capacity. 132 adult male (n=63) and female (n= 69) C57BL/6 mice were randomized to one of five interventions for twelve weeks: control (n= 27), high fat diet (HFD; n=26), HFD + Exe (n=28), HFD + Gen (n=27), or HFD + Exe + Gen (n=24). All HFD drinking water was supplemented with 42g sugar/L. Fecal pellets were collected, DNA extracted, and measured the microbial composition by sequencing the V4 of the 16S rRNA gene with Illumina. The mitochondrial oxidative capacity was assessed by measuring the enzymatic kinetic activity of the citrate synthase (CS) of forty-nine mice. This study found that Exe groups had a significantly higher bacterial richness compared to HFD + Gen or HFD group. Exe + Gen showed the synergistic effect to drive the GM towards the control group´s GM composition as we found Ruminococcus significantly more abundant in the HFD + Exe + Gen than the rest of the HFD groups. The study did not find preventive capacity in either of the interventions on the CS activity. Therefore, further research is needed to confirm the synergistic effect of Exe, Exe, and Gen on the gut bacterial richness and the capacity to prevent HFD-induced deleterious effect on GM and mitochondrial oxidative capacity.
ContributorsOrtega Santos, Carmen Patricia (Author) / Whisner, Corrie M (Thesis advisor) / Dickinson, Jared M (Committee member) / Katsanos, Christos (Committee member) / Gu, Haiwei (Committee member) / Liu, Li (Committee member) / Al-Nakkash, Layla (Committee member) / Arizona State University (Publisher)
Created2021
Description
The plateau pika (Ochotona curzoniae), a small burrowing lagomorph that occupies the high alpine grassland ecosystems of the Qinghai-Tibetan Plateau in western China, remains a controversial subject among policymakers and researchers. One line of evidence points to pikas being a pest, which has led to massive attempts to eradicate pika populations. Another point of view is that pikas are a keystone species and an ecosystem engineer in the grassland ecosystem of the QTP. The pika eradication program raises a difficult ethical and religious dilemma for local pastoralists, and is criticized for not being supported by scientific evidence. Complex interactions between pikas, livestock, and habitat condition are poorly understood. My dissertation research examines underpinning justifications of the pika poisoning program leading to these controversies. I investigated responses of pikas to habitat conditions with field experimental manipulations, and mechanisms of pika population recovery following pika removal. I present policy recommendations based on an environmental ethics framework and findings from the field experiments. After five years of a livestock grazing exclusion experiment and four years of pika monitoring, I found that grazing exclusion resulted in a decline of pika habitat use, which suggests that habitat conditions determine pika population density. I also found that pikas recolonized vacant burrow systems following removal of residents, but that distances travelled by dispersing pikas were extremely short (~50 m). Thus, current pika eradication programs, if allowed to continue, could potentially compromise local populations as well as biodiversity conservation on the QTP. Lethal management of pikas is a narrowly anthropocentric-based form of ecosystem management that has excluded value-pluralism, such as consideration of the intrinsic value of species and the important ecological role played by pikas. These conflicting approaches have led to controversies and policy gridlock. In response, I suggest that the on-going large-scale pika eradication program needs reconsideration. Moderation of stocking rates is required in degraded pika habitats, and Integrated Pest Management may be required when high stocking rate and high pika density coexist. A moderate level of livestock and pika density can be consistent with maintaining the integrity and sustainability of the QTP alpine steppe ecosystem.
ContributorsBadingqiuying (Author) / Smith, Andrew T. (Thesis advisor) / Wu, Jianguo (Committee member) / Minteer, Ben (Committee member) / Anderies, John (Committee member) / Harris, Richard B. (Committee member) / Arizona State University (Publisher)
Created2016