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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
In cold chain tracking systems, accuracy and flexibility across different temperatures ranges plays an integral role in monitoring biospecimen integrity. However, while two common cold chain tracking systems are currently available (electronic and physics/chemical), there is not an affordable cold chain tracking mechanism that can be applied to a variety of temperatures while maintaining accuracy for individual vials. Hence, our lab implemented our understanding of biochemical reaction kinetics to develop a new cold chain tracking mechanism using the permanganate/oxalic acid reaction. The permanganate/oxalic acid reaction is characterized by the reduction of permanganate (MnVII) to Mn(II) with Mn(II)-autocatalyzed oxidation of oxalate to CO2, resulting in a pink to colorless visual indicator change when the reaction system is not in the solid state (i.e., frozen or vitrified). Throughout our research, we demonstrate, (i) Improved reaction consistency and accuracy along with extended run times with the implementation of a nitric acid-based labware washing protocol, (ii) Simulated reaction kinetics for the maximum length reaction and 60-minute reaction based on previously developed MATLAB scripts (iii) Experimental reaction kinetics to verify the simulated MATLAB maximum and 60-minute reactions times (iv) Long-term stability of the permanganate/oxalic acid reaction with water or eutectic solutions of sodium perchlorate and magnesium perchlorate at -80°C (v) Reaction kinetics with eutectic solvents, sodium perchlorate and magnesium perchlorate, at 25°C, 4°C, and -8°C (vi) Accelerated reaction kinetics after the addition of varying concentrations of manganese perchlorate (vii) Reaction kinetics of higher concentration reaction systems (5x and 10x; for darker colors), at 25°C (viii) Long-term stability of the 10x higher concentration reaction at -80°C.
ContributorsLjungberg, Emil (Author) / Borges, Chad (Thesis director) / Levitus, Marcia (Committee member) / Williams, Peter (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor)
Created2022-12
Description
ABSTRACT Over the past several decades, the dilemma of free-roaming horses in the U.S. has proven to be one of the most divisive issues in management of public lands. According to federal land management agencies, without population regulation, horses can increase at the rate of 15-20% a year on arid rangelands with inadequate numbers of natural, large predators. Horses compete for valuable forage and water resources alongside cattle and native wildlife in delicate riparian areas highly susceptible to the negative ecological effects of soil compaction and overgrazing. Most U.S. management policies, therefore, call for increased removal of free-roaming horses as they are categorized as “un-authorized livestock” or "non-native" species. Wild horse advocates, however, continue to petition for improvement in animal welfare and expansion of the horses’ territory. With heightened social conflict spurred by animal rights and ecological concerns, not to mention the often-stark differences over what really “belongs” on the landscape, the success of appropriate management strategies hinges on managing agencies’ preparedness and ability to respond in a timely and inclusive manner. A critical element of the management context is the public’s views toward the wild horse and the science used to manage them. Synthesizing the vast literature in the history and philosophy of wildlife management in the American West, and utilizing an ethnographic and case study approach, my research examines the range of stakeholder concerns and analyzes the factors that have led to the disconnect between public values of wild horses and public policy for the management of the federally protected free-roaming horses in Arizona’s Apache-Sitgreaves National Forests.
ContributorsMurphree, Julie Joan (Author) / Minteer, Ben A. (Thesis advisor) / Schoon, Michael (Thesis advisor) / Bradshaw, Karen (Committee member) / Chew, Matthew (Committee member) / Arizona State University (Publisher)
Created2022
Description
Plasma and serum are the most commonly used liquid biospecimens in biomarker research. These samples may be subjected to several pre-analytical variables (PAVs) during collection, processing and storage. Exposure to thawed conditions (temperatures above -30 °C) is a PAV that is hard to control, and track and could provide misleading information, that fail to accurately reveal the in vivo biological reality, when unaccounted for. Hence, assays that can empirically check the integrity of plasma and serum samples are crucial. As a solution to this issue, an assay titled ΔS-Cys-Albumin was developed and validated. The reference range of ΔS-Cys-Albumin in cardio vascular patients was determined and the change in ΔS-Cys-Albumin values in different samples over time course incubations at room temperature, 4 °C and -20 °C were evaluated. In blind challenges, this assay proved to be successful in identifying improperly stored samples individually and as groups. Then, the correlation between the instability of several clinically important proteins in plasma from healthy and cancer patients at room temperature, 4 °C and -20 °C was assessed. Results showed a linear inverse relationship between the percentage of proteins destabilized and ΔS-Cys-Albumin regardless of the specific time or temperature of exposure, proving ΔS-Cys-Albumin as an effective surrogate marker to track the stability of clinically relevant analytes in plasma. The stability of oxidized LDL in serum at different temperatures was assessed in serum samples and it stayed stable at all temperatures evaluated. The ΔS-Cys-Albumin requires the use of an LC-ESI-MS instrument which limits its availability to most clinical research laboratories. To overcome this hurdle, an absorbance-based assay that can be measured using a plate reader was developed as an alternative to the ΔS-Cys-Albumin assay. Assay development and analytical validation procedures are reported herein. After that, the range of absorbance in plasma and serum from control and cancer patients were determined and the change in absorbance over a time course incubation at room temperature, 4 °C and -20 °C was assessed. The results showed that the absorbance assay would act as a good alternative to the ΔS-Cys-Albumin assay.
ContributorsJehanathan, Nilojan (Author) / Borges, Chad (Thesis advisor) / Guo, Jia (Committee member) / Van Horn, Wade (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
Communications around sustainability have been found to be incongruent with eliciting the transformative change required to address global climate change and its' repercussions. Recent research has been exploring storytelling in sustainability, specifically with an emphasis on reflexive and emancipatory methods. These methods encourage embracing and contextualizing complexity and intend to target entire cognitive hierarchies. This study explores the possibility of using emancipatory and reflexive storytelling as a tool to change attitudes pertaining to the Valley Metro Light Rail, an example of a complex sustainability mitigation effort. I explore this in four steps: 1) Conducted a pre-survey to gauge preexisting attitudes and predispositions; 2) Provided a narrative that uses storytelling methodologies of reflexivity and emancipation through a story about the light rail; 3) Conducted a post-survey to gauge attitude shift resulting from the narrative intervention; 4) Facilitated a focus group discussion to examine impact qualitatively. These steps intended to provide an answer to the question: How does emancipatory and reflexive storytelling impact affective, cognitive and conative attitudes regarding local alternative transportation? By using tripartite attitude model, qualitative and quantitative analysis this paper determines that reflexive and emancipatory storytelling impacts attitudinal structures. The impact is marginal in the survey response, though the shift indicated a narrowing of participant responses towards one another, indicative of participants subscribing to emancipation and reflexivity of their held attitudes. From the group discussion, it was evident from qualitative responses that participants engaged in emancipating themselves from their held attitudes and reflected upon them. In doing so they engaged in collaboration to make suggestions and suggest actions to help those with experiences that differed from their own. Though this research doesn’t provide conclusive evidence, it opens the door for future research to assess these methodologies as a tool to elicit shared values, beliefs and norms, which are necessary for collective action leading to transformative change in response to global climate change.
ContributorsSwanson, Jake Ryan (Author) / Roseland, Mark (Thesis advisor) / Larson, Kelli (Committee member) / Calhoun, Craig (Committee member) / Schoon, Michael (Committee member) / Arizona State University (Publisher)
Created2023
Description
Trace evidence is an essential component of forensic investigations. Anthropogenicmaterials such as fibers and glass have been well studied for use in forensic trace evidence, but the potential use of retroreflective beads found in soils for forensic investigations is largely unexplored. Retroreflective glass beads are tiny spheres mixed into pavement markings to create reflective surfaces to reduce lane departure accidents. Retroreflective glass beads are a potentially new source of trace evidence for forensic investigations.
Analysis of the spatial distribution and chemical compositions of retroreflective glass beads recovered from 17 soil samples were analyzed and compared to see if there are striking variations that can distinguish samples by source. Soil samples taken near marked roads showed significantly higher concentrations of glass beads, averaging from 0.18 bead/g of soil sample to 587 beads/g of soil, while soil samples taken near unmarked roads had average range of concentration of 0 bead/g of soil to 0.21 bead/g of soil. Retroreflective glass beads come from pavement markings, thus soil samples near marked roads are expected to have higher concentrations of glass beads. Analysis of spatial distribution of glass beads showed that as sample collection moved further from the road, concentration of glass beads decreased.
ICP-MS results of elemental concentrations for each sample showed discriminative differences between samples, for most of the elements. An analysis of variance for elemental concentrations was conducted, and results showed statistically significant differences, beyond random chance alone for half of the elements analyzed. For forensic comparisons, a significant difference in even just one element is enough to conclude that the samples came from different sources. The elemental concentrations of glass beads collected from the same location, but of varying differences, was also analyzed. ANOVA results show significant differences for only one or two elements. A pair-wise t-test was conducted to determine which elements are most discriminative among all the samples. Rubidium was found to be the most discriminative, showing significant difference for 67% of the pairs. Beryllium, potassium, and manganese were also highly discriminative, showing significant difference for at least 50% of all the pairs.
ContributorsGomez, Janelle Kate Pacifico (Author) / Montero, Shirly (Thesis advisor) / Herckes, Pierre (Thesis advisor) / Borges, Chad (Committee member) / Gordon, Gwyneth (Committee member) / Arizona State University (Publisher)
Created2023
Description
Understanding the dynamic interactions between humans and wildlife is essential to establishing sustainable wildlife-based ecotourism (WBE). Animal behavior exists within a complex feedback loop that affects overall ecosystem function, tourist satisfaction, and socioeconomics of local communities. However, the specific value that animal behavior plays in provisioning ecosystem services has not been thoroughly evaluated. People enjoy activities that facilitate intimate contact with animals, and there are many perceived benefits associated with these experiences, such as encouraging pro-environmental attitudes that can lead to greater motivation for conservation. There is extensive research on the effects that unregulated tourism activity can have on wildlife behavior, which include implications for population health and survival. Prior to COVID-19, WBE was developing rapidly on a global scale, and the pause in activity caused by the pandemic gave natural systems the chance to recover from environmental damage from over-tourism and provided insights into how tourism could be less impactful in the future. Until now it has been undetermined how changes in animal behavior can alter the relationships and socioeconomics of this multidimensional system. This dissertation provides a thorough exploration of the behavioral, ecological, and economic parameters required to model biosocial interactions and feedbacks within the whale watching system in Las Perlas Archipelago, Panama. Through observational data collected in the field, this project assessed how unmanaged whale watching activity is affecting the behavior of Humpback whales in the area as well as the socioeconomic and conservation contributions of the industry. Additionally, it is necessary to consider what a sustainable form of wildlife tourism might be, and whether the incorporation of technology will help enhance visitor experience while reducing negative impacts on wildlife. To better ascertain whether this concept of this integration would be favorably viewed, a sample of individuals was surveyed about their experiences about using technology to enhance their interactions with nature. This research highlights the need for more deliberate identification and incorporation of the perceptions of all stakeholders (wildlife included) to develop a less-impactful WBE industry that provides people with opportunities to establish meaningful relationships with nature that motivate them to help meet the conservation challenges of today.
ContributorsSurrey, Katie (Author) / Gerber, Leah (Thesis advisor) / Guzman, Hector (Committee member) / Minteer, Ben (Committee member) / Schoon, Michael (Committee member) / Arizona State University (Publisher)
Created2023
Description
Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as well as caregivers to maintain appropriate glucose levels. The majority of T1D patients have antibodies to one or more antigens: insulin, IA-2, GAD65, and ZnT8. Although antibodies are detectable years before symptoms occur, the initiating factors and mechanisms of progression towards β-cell destruction are still not known. The search for new autoantibodies to elucidate the autoimmune process in diabetes has been slow, with proteome level screenings on native proteins only finding a few minor antigens. Post-translational modifications (PTM)—chemical changes that occur to the protein after translation is complete—are an unexplored way a self-protein could become immunogenic. This dissertation presents the first large sale screening of autoantibodies in T1D to nitrated proteins. The Contra Capture Protein Array (CCPA) allowed for fresh expression of hundreds of proteins that were captured on a secondary slide by tag-specific ligand and subsequent modification with peroxynitrite. The IgG and IgM humoral response of 48 newly diagnosed T1D subjects and 48 age-matched controls were screened against 1632 proteins highly or specifically expressed in pancreatic cells. Top targets at 95% specificity were confirmed with the same serum samples using rapid antigenic protein in situ display enzyme-linked immunosorbent assay (RAPID ELISA) a modified sandwich ELISA employing the same cell-free expression as the CCPA. For validation, 8 IgG and 5 IgM targets were evaluated with an independent serum sample set of 94 T1D subjects and 94 controls. The two best candidates at 90% specificity were estrogen receptor 1 (ESR1) and phosphatidylinositol 4-kinase type 2 beta (PI4K2B) which had sensitivities of 22% (p=.014) and 25% (p=.045), respectively. Receiver operating characteristic (ROC) analyses found an area under curve (AUC) of 0.6 for ESR1 and 0.58 for PI4K2B. These studies demonstrate the ability and value for high-throughput autoantibody screening to modified antigens and the frequency of Type 1 diabetes.
ContributorsHesterman, Jennifer (Author) / LaBaer, Joshua (Thesis advisor) / Borges, Chad (Committee member) / Sweazea, Karen (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
University-level sustainability education in Western academia attempts to focus on eliminating future harm to people and the planet. However, Western academia as an institution upholds systems of oppression and reproduces settler colonialism. This reproduction is antithetical to sustainability goals as it continues patterns of Indigenous erasure and extractive relationships to the Land that perpetuate violence towards people and the planet. Sustainability programs, however, offer several frameworks, including resilience, that facilitate critical interrogations of social-ecological systems. In this thesis, I apply the notion of resilience to the perpetuation of settler colonialism within university-level sustainability education. Specifically, I ask: How is settler colonialism resilient in university-level sustainability education? How are, or could, sustainability programs in Western academic settings address settler colonialism? Through a series of conversational interviews with faculty and leadership from Arizona State University School of Sustainability, I analyzed how university-level sustainability education is both challenging and shaped by settler colonialism. These interviews focused on faculty perspectives on the topic and related issues; the interviews were analyzed using thematic coding in NVivo software. The results of this project highlight that many faculty members are already concerned with and focused on challenging settler colonialism, but that settler colonialism remains resilient in this system due to feedback loops at the personal level and reinforcing mechanisms at the institutional level. This research analyzes these feedback loops and reinforcing mechanisms, among others, and supports the call for anti-colonial and decolonial reconstruction of curriculum, as well as a focus on relationship building, shifting of mindset, and school-wide education on topics of white supremacy, settler colonialism, and systems of oppression in general.
ContributorsBills, Haven (Author) / Klinsky, Sonja (Thesis advisor) / Goebel, Janna (Committee member) / Schoon, Michael (Committee member) / Arizona State University (Publisher)
Created2022