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Acetylcholinesterase (AChE) inhibition by chemical toxicants such as organophosphates, nerve agents, and carbamates can lead to a series of adverse health outcomes including seizures, coma, and death. An adverse outcome pathway (AOP) is a framework that describes a series of biologically measurable key events (KEs) leading from some molecular initiating

Acetylcholinesterase (AChE) inhibition by chemical toxicants such as organophosphates, nerve agents, and carbamates can lead to a series of adverse health outcomes including seizures, coma, and death. An adverse outcome pathway (AOP) is a framework that describes a series of biologically measurable key events (KEs) leading from some molecular initiating event (MIE) to an adverse outcome (AO) of regulatory significance, all developed and hosted in the AOP Wiki. A quantitative AOP (qAOP) is a mathematical model that predicts how perturbations in the MIE affect KEs based on the key event relationships (KERs) that define the AOP. The purpose of this thesis was to expand upon the KERs that define the AOP for AChE inhibition leading to neurodegeneration in order to better understand the effects of AChE inhibitors and the risks they pose to ecosystems, wildlife, and human health. In order to reduce the resources and time spent for chemical toxicity testing, a qAOP was developed based on the available quantitative data and models that supported the AOP. A literature review for the collection of qualitative evidence and quantitative data in support of the AOP was performed resulting in further expansion of the relationships between key events (KERs) through construction of additional KER description pages. A model evaluation was performed by comparing the qAOP model predictions with experimental data, with a subsequent sensitivity analysis of unknown parameters. The qAOP model simulates the MIE through its fifth KE (KE 5) and KE 7. Model predictions compared to experimentally measured data either under- or overpredicting multiple KEs warranting additional refinement such as a formal parameter optimization. Overall, more data amenable to qAOP model development are needed. To aid qAOP model development, the presentation of data in the AOPWiki may be improved by presenting the quantitative data in the AOP Wiki in a tabular format and allowing for the hosting of mathematical models or raw data. With these recommendations in mind, and through continued AOP construction in the AOP Wiki, new qAOP models will be developed, ultimately supporting chemical risk assessment and the mitigation of effects upon exposed individuals and wildlife populations.
ContributorsSinitsyn, Dennis (Author) / Watanabe, Karen (Thesis advisor) / Vinas, Natalia (Committee member) / Wirkus, Stephen (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Mycobacterium leprae, the causative agent of Hansen’s disease (leprosy), has plagued humans and other animal species for millennia and remains of concern to public health throughout the world today. Recent research into the expanded use of medical tissues preserved as formalin-fixed, paraffin-embedded samples (FFPE), opened the door for the study

Mycobacterium leprae, the causative agent of Hansen’s disease (leprosy), has plagued humans and other animal species for millennia and remains of concern to public health throughout the world today. Recent research into the expanded use of medical tissues preserved as formalin-fixed, paraffin-embedded samples (FFPE), opened the door for the study of M. leprae DNA from preserved skin samples. However, problems persist with damage to the DNA including fragmentation and cross linkage. This study evaluated two methods commonly used for the recovery of host DNA from FFPE samples for their efficacy in extracting pathogen DNA (hot alkaline lysis protocol and QIAGEN QIAamp FFPE DNA kit). Twenty FFPE skin samples collected from 1995-2015 from human subjects in the Pacific Islands suffering from M. leprae infection, each exhibiting a range of bacillary loads, were analyzed to determine which extraction method was most successful in terms of ability to consistently yield reliable, robust traces of M. leprae infection. This study further examined these samples to understand the phylogeny of leprosy in the region, where gaps in the evolutionary history of M. leprae persist. DNA recovery from paired samples was similar using either method. However, by extending the incubation time of post-paraffin removal sample lysis, both protocols were more likely to yield positive traces of M. leprae, with this enhancement being especially evident in paucibacillary samples with low bacterial presence. The qPCR assay findings suggest that the hot alkaline procedure is most likely to yield positive identification of infection in these traditionally challenging samples.
ContributorsKing, Felicia Clarice (Author) / Stone, Anne (Thesis advisor) / Wilson, Melissa (Committee member) / Buetow, Ken (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Genome-wide, single nucleotide polymorphisms (SNPs) and germination data were analyzed to better understand species delimitation and salt-tolerance within the legume genus Medicago. Molecular phylogenies revealed that the widely-used, genomic model line R108 and two deeply divergent accessions of Medicago truncatula are in fact more closely related to Medicago littoralis than

Genome-wide, single nucleotide polymorphisms (SNPs) and germination data were analyzed to better understand species delimitation and salt-tolerance within the legume genus Medicago. Molecular phylogenies revealed that the widely-used, genomic model line R108 and two deeply divergent accessions of Medicago truncatula are in fact more closely related to Medicago littoralis than to other accessions representing Medicago truncatula. This result was supported by germination data wherein the two accessions representing deeply divergent Medicago truncatula demonstrated salt-tolerance that was more similar to Medicago littoralis than to other accessions of Medicago truncatula. Molecular phylogenies revealed that two additional accessions representing deeply divergent Medicago truncatula appear to be more closely related to Medicago italica than to other accessions representing Medicago truncatula. The results of the present study elucidate complex evolutionary relationships and contribute to the present understanding of existing salt-tolerance within Medicago.
ContributorsHopkins, Andrew David (Author) / Wojciechowski, Martin (Thesis advisor) / Park, Yujin (Committee member) / Steele, Kelly (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Biogeography places the geographical distribution of biodiversity in an evolutionary context. Ants (Hymenoptera: Formicidae), being a group of ubiquitous, ecologically dominant, and diverse insects, are useful model systems to understand the evolutionary origins and mechanisms of biogeographical patterns across spatial scales. On a global scale, ants have been used to

Biogeography places the geographical distribution of biodiversity in an evolutionary context. Ants (Hymenoptera: Formicidae), being a group of ubiquitous, ecologically dominant, and diverse insects, are useful model systems to understand the evolutionary origins and mechanisms of biogeographical patterns across spatial scales. On a global scale, ants have been used to test hypotheses on the origin and maintenance of the remarkably consistent latitudinal diversity gradient where biodiversity peaks in the equatorial tropics and decreases towards the poles. Additionally, ants have been used to posit and test theories of island biogeography such as the mechanisms of the species-area relationship, being the increase of biodiversity with cumulative land area. However, there are still unanswered questions about ant biogeography such as how specialized life histories contribute to their global biogeographical patterns. Furthermore, there remain island systems in the world’s biodiversity hotspots that harbor much less ant species than predicted by the species-area relationship, which potentially suggests a place ripe for discovery. In this dissertation, I use natural history, taxonomic, geographic, and phylogenetic data to study ant biodiversity and biogeography across spatial scales. First, I study the global biodiversity and biogeography of a specialized set of symbiotic interactions between ant species, here referred to as myrmecosymbioses, with an emphasis on social parasitism where one species exploits the parental care behavior and social colony environment of another species. In addition to characterizing a new myrmecosymbiosis, I use a global biogeographic and phylogenetic dataset to show that ant social parasitism is distributed along an inverse latitudinal diversity gradient where species richness and independent evolutionary origins of social parasitism peak within the northern hemisphere where the least free-living ant diversity exists. Second, I study the unexplored ant fauna of the Vanuatuan archipelago in the South Pacific. Using approximately 10,000 Vanuatuan ant specimens coupled with phylogenomics, I fill in a historical knowledge gap of South Pacific ant biogeography and demonstrate that the Vanuatuan ant fauna is a novel biodiversity hotspot. With these studies, I provide insights into how specialized life histories and unique island biotas shape the global distribution of biodiversity in different ways, especially in the ants.
ContributorsGray, Kyle William (Author) / Rabeling, Christian (Thesis advisor) / Martins, Emilia (Committee member) / Taylor, Jesse (Committee member) / Pratt, Stephen (Committee member) / Wojciechowski, Martin (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Evolution is a key feature of undergraduate biology education: the AmericanAssociation for the Advancement of Science (AAAS) has identified evolution as one of the five core concepts of biology, and it is relevant to a wide array of biology-related careers. If biology instructors want students to use evolution to address scientific challenges post-graduation,

Evolution is a key feature of undergraduate biology education: the AmericanAssociation for the Advancement of Science (AAAS) has identified evolution as one of the five core concepts of biology, and it is relevant to a wide array of biology-related careers. If biology instructors want students to use evolution to address scientific challenges post-graduation, students need to be able to apply evolutionary principles to real-life situations, and accept that the theory of evolution is the best scientific explanation for the unity and diversity of life on Earth. In order to help students progress on both fronts, biology education researchers need surveys that measure evolution acceptance and assessments that measure students’ ability to apply evolutionary concepts. This dissertation improves the measurement of student understanding and acceptance of evolution by (1) developing a novel Evolutionary Medicine Assessment that measures students’ ability to apply the core principles of Evolutionary Medicine to a variety of health-related scenarios, (2) reevaluating existing measures of student evolution acceptance by using student interviews to assess response process validity, and (3) correcting the validity issues identified on the most widely-used measure of evolution acceptance - the Measure of Acceptance of the Theory of Evolution (MATE) - by developing and validating a revised version of this survey: the MATE 2.0.
ContributorsMisheva, Anastasia Taya (Author) / Brownell, Sara (Thesis advisor) / Barnes, Elizabeth (Committee member) / Collins, James (Committee member) / Cooper, Katelyn (Committee member) / Sterner, Beckett (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Aggregation is a fundamental principle of animal behavior; it is especially significant tohighly social species, like ants. Ants typically aggregate their workers and brood in a central nest, potentially due to advantages in colony defense and regulation of the environment. In many ant species, when a colony must abandon its

Aggregation is a fundamental principle of animal behavior; it is especially significant tohighly social species, like ants. Ants typically aggregate their workers and brood in a central nest, potentially due to advantages in colony defense and regulation of the environment. In many ant species, when a colony must abandon its nest, it can effectively reach consensus on a new home. Ants of the genus Temnothorax have become a model for this collective decision-making process, and for decentralized cognition more broadly. Previous studies examine emigration by well-aggregated colonies, but can these ants also reach consensus when the colony has been scattered? Such scattering may readily occur in nature if the nest is disturbed by natural or man- made disasters. In this exploratory study, Temnothorax rugatulus colonies were randomly scattered in an arena and presented with a binary equal choice of nest sites. Findings concluded that the colonies were able to re-coalesce, however consensus is more difficult than for aggregated colonies and involved an additional primary phase of multiple temporary aggregations eventually yielding to reunification. The maximum percent of colony utilization for these aggregates was reached within the first hour, after which point, consensus tended to rise as aggregation decreased. Small, but frequent, aggregates formed within the first twenty minutes and remained and dissolved to the nest by varying processes. Each colony included a clump containing the queen, with the majority of aggregates containing at least one brood item. These findings provide additional insight to house-hunting experiments in more naturally challenging circumstances, as well as aggregation within Temnothorax colonies.
ContributorsGoodland, Brooke (Author) / Shaffer, Zachary (Thesis advisor) / Pratt, Stephen (Thesis advisor) / Pavlic, Theodore (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The purpose of this paper is to create awareness around breast cancer risk factorsand screening methods. Five overarching intrinsic risk factors, including: the patient’s age at the time of diagnosis, race, familial susceptibility, and the role of natural hormone changes, and one extrinsic risk factor, dietary habits, were selected for consideration. Along with

The purpose of this paper is to create awareness around breast cancer risk factorsand screening methods. Five overarching intrinsic risk factors, including: the patient’s age at the time of diagnosis, race, familial susceptibility, and the role of natural hormone changes, and one extrinsic risk factor, dietary habits, were selected for consideration. Along with risk factors, four screening methods were taken into consideration. These included self-breast exams, mammograms, magnetic resonance imaging (MRI), and ultrasound. The recommendation of screening methods was then determined in relation to a women’s risk for breast cancer. Two categories of risk (average and high risk) were defined and the recommended screening methods were determined based on the risk. Overall, mammography was found to be a useful tool in both average and high risk women. For high risk women, mammography with MRI had a greater sensitivity and was able to detect more breast cancers. More research needs to be conducted on the efficacy of Breast MRI, Ultrasound, and breast self-exams as supplemental tools to mammography in both average and high-risk women
ContributorsTodd, Julia M (Author) / Compton, Carolyn (Thesis advisor) / Pepin, Susan (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The alarming decline of insect pollinators is due in part to agrochemical exposure and climate warming. This thesis focuses on understanding how exposure to a commonly used fungicide and high air temperature affect the flight behavior and physiology of the very important commercial pollinator, Apis mellifera. I found that honey

The alarming decline of insect pollinators is due in part to agrochemical exposure and climate warming. This thesis focuses on understanding how exposure to a commonly used fungicide and high air temperature affect the flight behavior and physiology of the very important commercial pollinator, Apis mellifera. I found that honey bees reared on pollen contaminated with field-realistic levels of a fungicide (Pristine®) commonly applied to almond blossoms before pollination had smaller thoraxes, possibly due to inhibition of protein digestion, plausibly reducing flight capability. By flying unloaded bees in low density air to elicit maximal performance, I found that consumption of high doses of fungicide during development inhibited maximal flight performance, but consumption of field-realistic doses did not. To understand climatic-warming effects on honey bees, I flew unloaded foragers at various air densities and temperatures to assess the effects of flight muscle temperature (29 to 44°C) on maximal aerobic metabolism. Flight metabolic rate peaked at a muscle temperature of 39°C and decreased by ~2% per degree below and ~5% per degree above this optimum. Carrying nectar loads increased flight muscle temperatures and flight metabolism of foragers flying at air temperatures of 20 or 30°C. Yet, remarkably, bees flying at 40°C were able to carry loads without heating up or increasing metabolic rate. Bees flying at 40°C increased evaporative cooling and decreased metabolic heat production to thermoregulate. High speed video revealed that bees flying at 40°C air temperature lowered their wing beat frequency while increasing stroke amplitude, increasing flight efficiency. My data also suggests that cooler bees use wing kinematic strategies that increase flight stability and maneuverability while generating excess heat that warms their flight muscle toward optimum. High water loss rates during flight likely limit foraging in dry air temperatures above 46°C, suggesting that CTmax measures of resting honey bees significantly overestimate when high air temperature will negatively impact flight and foraging.
ContributorsGlass, Jordan Robert (Author) / Harrison, Jon F. (Thesis advisor) / Denardo, Dale F. (Committee member) / Dudley, Robert (Committee member) / Fewell, Jennifer H. (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Phenotypic evolution is of great significance within biology, as it is the culmination of the influence of key evolutionary factors on the expression of genotypes. Deeper studies of the fundamental components, such as fitness effects of mutations and genetic variance within a population, allow one to predict the evolutionary trajectory

Phenotypic evolution is of great significance within biology, as it is the culmination of the influence of key evolutionary factors on the expression of genotypes. Deeper studies of the fundamental components, such as fitness effects of mutations and genetic variance within a population, allow one to predict the evolutionary trajectory of phenotypic evolution. In this regard, how much the change in mutational variance and the ongoing natural selection influence the rate of phenotypic evolution has yet to be fully understood. Therefore, this study measured mutational variances and the increasing rate of genetic variance during the experimental evolution of Escherichia coli populations, focusing on two growth-related traits, the populational maximum growth rate and carrying capacity. Mutational variances were measured by mutation-accumulation experiments, which allowed for the analysis of the effects of spontaneous mutations on growth-related traits in the absence of selection. This analysis revealed that some evolved populations developed a higher mutational variance for growth-related traits. Further investigation showed that most evolved populations have also developed a greater mutational effect, which could explain the increase in mutational variance. Finally, the genetic variances for most evolved populations are lower than expected in the absence of selection, and the involvement of either stabilizing or directional selection is evident. Future experiments with a larger sample size of experimentally evolved populations, as well as more intermediate timepoints during experimental evolution, may provide further insight regarding the complexities of the evolutionary outcomes of these traits.
ContributorsGonzales, Jadon (Author) / Lynch, Michael (Thesis advisor) / Geiler-Samerotte, Kerry (Committee member) / Ho, Wei-Chin (Committee member) / Arizona State University (Publisher)
Created2023
Description
Recovering high-quality DNA from thermally altered human remains poses a significant challenge for research and law enforcement agencies due to high levels of DNA degradation resulting from exposure to extremely high temperatures (e.g., fire). The current standard practice for the DNA identification of badly burned skeletal remains is to extract

Recovering high-quality DNA from thermally altered human remains poses a significant challenge for research and law enforcement agencies due to high levels of DNA degradation resulting from exposure to extremely high temperatures (e.g., fire). The current standard practice for the DNA identification of badly burned skeletal remains is to extract DNA from dense cortical bone collected from recovered skeletal elements. Some of the problems associated with this method are that it requires specialized equipment and training, is highly invasive (involving the physical destruction of sample material), time-consuming, and does not reliably guarantee the successful identification of the remains in question. At low-medium levels of thermal exposure, charred tissue is often adhered to these skeletal remains and typically discarded. In cases where burned/charred tissue is recoverable, it has the potential to be a more efficient alternative to the sampling of cortical bone. However, little has been done to test the viability of thermally altered soft tissue in terms of DNA identification to date. Burned/charred tissue was collected from skeletal samples provided by the University of Tennessee Forensic Anthropology Center, as a part of a controlled burn from donor individuals, for downstream laboratory processing and DNA analysis as part of the Stone Lab (Arizona State University, School of Human Evolution and Social Change). DNA from this charred tissue was extracted using the Qiagen DNeasy Blood and Tissue Kit, and resulting yields were quantified via fluorometry using the Qubit Fluorometer 2.0 and Agilent TapeStation 4200 High-Sensitivity D5000 assay. It was found that between the temperatures of ~200-300 ℃ (burn category 2) and ~300-350 ℃ (burn category 3), tissue was the most efficient extraction type, especially from tissue taken from the surface of the ilium and the rib. As for bone, both the Dabney and the Loreille protocol performed similarly, so choice in extraction type comes down to personal preference, type of equipment on hand, and training. Although, for samples with low input material, the Dabney protocol is optimal.
ContributorsCoffman, Amber (Author) / Stone, Anne C (Thesis advisor) / Parker, Cody (Committee member) / Kanthaswamy, Sreetharan (Committee member) / Arizona State University (Publisher)
Created2023