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ABSTRACT 1. Aposematic signals advertise prey distastefulness or metabolic unprofitability to potential predators and have evolved independently in many prey groups over the course of evolutionary history as a means of protection from predation. Most aposematic signals investigated to date exhibit highly chromatic patterning; however, relatives in these toxic groups

ABSTRACT 1. Aposematic signals advertise prey distastefulness or metabolic unprofitability to potential predators and have evolved independently in many prey groups over the course of evolutionary history as a means of protection from predation. Most aposematic signals investigated to date exhibit highly chromatic patterning; however, relatives in these toxic groups with patterns of very low chroma have been largely overlooked. 2. We propose that bright displays with low chroma arose in toxic prey species because they were more effective at deterring predation than were their chromatic counterparts, especially when viewed in relatively low light environments such as forest understories. 3. We analyzed the reflectance and radiance of color patches on the wings of 90 tropical butterfly species that belong to groups with documented toxicity that vary in their habitat preferences to test this prediction: Warning signal chroma and perceived chromaticity are expected to be higher and brightness lower in species that fly in open environments when compared to those that fly in forested environments. 4. Analyses of the reflectance and radiance of warning color patches and predator visual modeling support this prediction. Moreover, phylogenetic tests, which correct for statistical non-independence due to phylogenetic relatedness of test species, also support the hypothesis of an evolutionary correlation between perceived chromaticity of aposematic signals and the flight habits of the butterflies that exhibit these signals.
ContributorsDouglas, Jonathan Marion (Author) / Rutowski, Ronald L (Thesis advisor) / Gadau, Juergen (Committee member) / McGraw, Kevin J. (Committee member) / Arizona State University (Publisher)
Created2013
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Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies).

Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
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The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with

The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
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A notable feature of advanced eusocial insect groups is a division of labor within the sterile worker caste. However, the physiological aspects underlying the differentiation of behavioral phenotypes are poorly understood in one of the most successful social taxa, the ants. By starting to understand the foundations on which social

A notable feature of advanced eusocial insect groups is a division of labor within the sterile worker caste. However, the physiological aspects underlying the differentiation of behavioral phenotypes are poorly understood in one of the most successful social taxa, the ants. By starting to understand the foundations on which social behaviors are built, it also becomes possible to better evaluate hypothetical explanations regarding the mechanisms behind the evolution of insect eusociality, such as the argument that the reproductive regulatory infrastructure of solitary ancestors was co-opted and modified to produce distinct castes. This dissertation provides new information regarding the internal factors that could underlie the division of labor observed in both founding queens and workers of Pogonomyrmex californicus ants, and shows that changes in task performance are correlated with differences in reproductive physiology in both castes. In queens and workers, foraging behavior is linked to elevated levels of the reproductively-associated juvenile hormone (JH), and, in workers, this behavioral change is accompanied by depressed levels of ecdysteroid hormones. In both castes, the transition to foraging is also associated with reduced ovarian activity. Further investigation shows that queens remain behaviorally plastic, even after worker emergence, but the association between JH and behavioral bias remains the same, suggesting that this hormone is an important component of behavioral development in these ants. In addition to these reproductive factors, treatment with an inhibitor of the nutrient-sensing pathway Target of Rapamycin (TOR) also causes queens to become biased towards foraging, suggesting an additional sensory component that could play an important role in division of labor. Overall, this work provides novel identification of the possible regulators behind ant division of labor, and suggests how reproductive physiology could play an important role in the evolution and regulation of non-reproductive social behaviors.
ContributorsDolezal, Adam G (Author) / Amdam, Gro V (Thesis advisor) / Brent, Colin S. (Committee member) / Gadau, Juergen (Committee member) / Hoelldobler, Bert (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
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The repression of reproductive competition and the enforcement of altruism are key components to the success of animal societies. Eusocial insects are defined by having a reproductive division of labor, in which reproduction is relegated to one or few individuals while the rest of the group members maintain the colony

The repression of reproductive competition and the enforcement of altruism are key components to the success of animal societies. Eusocial insects are defined by having a reproductive division of labor, in which reproduction is relegated to one or few individuals while the rest of the group members maintain the colony and help raise offspring. However, workers have retained the ability to reproduce in most insect societies. In the social Hymenoptera, due to haplodiploidy, workers can lay unfertilized male destined eggs without mating. Potential conflict between workers and queens can arise over male production, and policing behaviors performed by nestmate workers and queens are a means of repressing worker reproduction. This work describes the means and results of the regulation of worker reproduction in the ant species Aphaenogaster cockerelli. Through manipulative laboratory studies on mature colonies, the lack of egg policing and the presence of physical policing by both workers and queens of this species are described. Through chemical analysis and artificial chemical treatments, the role of cuticular hydrocarbons as indicators of fertility status and the informational basis of policing in this species is demonstrated. An additional queen-specific chemical signal in the Dufour's gland is discovered to be used to direct nestmate aggression towards reproductive competitors. Finally, the level of actual worker-derived males in field colonies is measured. Together, these studies demonstrate the effectiveness of policing behaviors on the suppression of worker reproduction in a social insect species, and provide an example of how punishment and the threat of punishment is a powerful force in maintaining cooperative societies.
ContributorsSmith, Adrian A. (Author) / Liebig, Juergen (Thesis advisor) / Hoelldobler, Bert (Thesis advisor) / Gadau, Juergen (Committee member) / Johnson, Robert A. (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
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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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Gene-centric theories of evolution by natural selection have been popularized and remain generally accepted in both scientific and public paradigms. While gene-centrism is certainly parsimonious, its explanations fall short of describing two patterns of evolutionary and social phenomena: the evolution of sex and the evolution of social altruism. I review

Gene-centric theories of evolution by natural selection have been popularized and remain generally accepted in both scientific and public paradigms. While gene-centrism is certainly parsimonious, its explanations fall short of describing two patterns of evolutionary and social phenomena: the evolution of sex and the evolution of social altruism. I review and analyze current theories on the evolution of sex. I then introduce the conflict presented to gene-centric evolution by social phenomena such as altruism and caste sterility in eusocial insects. I review gene-centric models of inclusive fitness and kin selection proposed by Hamilton and Maynard Smith. Based their assumptions, that relatedness should be equal between sterile workers and reproductives, I present several empirical examples that conflict with their models. Following that, I introduce a unique system of genetic caste determination (GCD) observed in hybrid populations of two sister-species of seed harvester ants, Pogonomyrmex rugosus and Pogonomyrmex barbatus. I review the evidence for GCD in those species, followed by a critique of the current gene-centric models used to explain it. In chapter two I present my own theoretical model that is both simple and extricable in nature to explain the origin, evolution, and maintenance of GCD in Pogonomyrmex. Furthermore, I use that model to fill in the gaps left behind by the contributing authors of the other GCD models. As both populations in my study system formed from inter-specific hybridization, I review modern discussions of heterosis (also called hybrid vigor) and use those to help explain the ecological competitiveness of GCD. I empirically address the inbreeding depression the lineages of GCD must overcome in order to remain ecologically stable, demonstrating that as a result of their unique system of caste determination, GCD lineages have elevated recombination frequencies. I summarize and conclude with an argument for why GCD evolved under selective mechanisms which cannot be considered gene-centric, providing evidence that natural selection can effectively operate on non-heritable genotypes appearing in groups and other social contexts.
ContributorsJacobson, Neal (Author) / Gadau, Juergen (Thesis advisor) / Laubichler, Manfred (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2012
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Here I present a phylogeographic study of at least six reproductively isolated lineages of harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: four of the identified lineages are divided into two pairs, and each pair has evolved

Here I present a phylogeographic study of at least six reproductively isolated lineages of harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: four of the identified lineages are divided into two pairs, and each pair has evolved under a mutualistic system that necessitates sympatry. These paired lineages are dependent upon one another because interlineage matings within each pair are the sole source of hybrid F1 workers; these workers build and sustain the colonies, facilitating the production of the reproductive caste, which results solely from intralineage fertilizations. This system of genetic caste determination (GCD) maintains genetic isolation among these closely related lineages, while simultaneously requiring co-expansion and emigration as their distributions have changed over time. Previous studies have also demonstrated that three of the four lineages displaying this unique genetic caste determination phenotype are of hybrid origin. Thus, reconstructing the phylogenetic and geographic history of this group allows us to evaluate past insights and plan future inquiries in a more complete historical biogeographic context. Using mitochondrial DNA sequences sampled across most of the morphospecies' ranges in the U.S. and Mexico, I employed several methods of phylogenetic and DNA sequence analysis, along with comparisons to geological, biogeographic, and phylogeographic studies throughout the sampled regions. These analyses on Pogonomyrmex harvester ants reveal a complex pattern of vicariance and dispersal that is largely concordant with models of late Miocene, Pliocene, and Pleistocene range shifts among various arid-adapted taxa in North America.
ContributorsMott, Brendon (Author) / Gadau, Juergen (Thesis advisor) / Fewell, Jennifer (Committee member) / Anderson, Kirk (Committee member) / Arizona State University (Publisher)
Created2012
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In social insect colonies, as with individual animals, the rates of biological processes scale with body size. The remarkable explanatory power of metabolic allometry in ecology and evolutionary biology derives from the great diversity of life exhibiting a nonlinear scaling pattern in which metabolic rates are not proportional to mass,

In social insect colonies, as with individual animals, the rates of biological processes scale with body size. The remarkable explanatory power of metabolic allometry in ecology and evolutionary biology derives from the great diversity of life exhibiting a nonlinear scaling pattern in which metabolic rates are not proportional to mass, but rather exhibit a hypometric relationship with body size. While one theory suggests that the supply of energy is a major physiological constraint, an alternative theory is that the demand for energy is regulated by behavior. The central hypothesis of this dissertation research is that increases in colony size reduce the proportion of individuals actively engaged in colony labor with consequences for energetic scaling at the whole-colony level of biological organization. A combination of methods from comparative physiology and animal behavior were developed to investigate scaling relationships in laboratory-reared colonies of the seed-harvester ant, Pogonomyrmex californicus. To determine metabolic rates, flow-through respirometry made it possible to directly measure the carbon dioxide production and oxygen consumption of whole colonies. By recording video of colony behavior, for which ants were individually paint-marked for identification, it was possible to reconstruct the communication networks through which information is transmitted throughout the colony. Whole colonies of P. californicus were found to exhibit a robust hypometric allometry in which mass-specific metabolic rates decrease with increasing colony size. The distribution of walking speeds also scaled with colony size so that larger colonies were composed of relatively more inactive ants than smaller colonies. If colonies were broken into random collections of workers, metabolic rates scaled isometrically, but when entire colonies were reduced in size while retaining functionality (queens, juveniles, workers), they continued to exhibit a metabolic hypometry. The communication networks in P. californicus colonies contain a high frequency of feed-forward interaction patterns consistent with those of complex regulatory systems. Furthermore, the scaling of these communication pathways with size is a plausible mechanism for the regulation of whole-colony metabolic scaling. The continued development of a network theory approach to integrating behavior and metabolism will reveal insights into the evolution of collective animal behavior, ecological dynamics, and social cohesion.
ContributorsWaters, James S., 1983- (Author) / Harrison, Jon F. (Thesis advisor) / Quinlan, Michael C. (Committee member) / Pratt, Stephen C. (Committee member) / Fewell, Jennifer H. (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
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For interspecific mutualisms, the behavior of one partner can influence the fitness of the other, especially in the case of symbiotic mutualisms where partners live in close physical association for much of their lives. Behavioral effects on fitness may be particularly important if either species in these long-term relationships displays

For interspecific mutualisms, the behavior of one partner can influence the fitness of the other, especially in the case of symbiotic mutualisms where partners live in close physical association for much of their lives. Behavioral effects on fitness may be particularly important if either species in these long-term relationships displays personality. Animal personality is defined as repeatable individual differences in behavior, and how correlations among these consistent traits are structured is termed behavioral syndromes. Animal personality has been broadly documented across the animal kingdom but is poorly understood in the context of mutualisms. My dissertation focuses on the structure, causes, and consequences of collective personality in Azteca constructor colonies that live in Cecropia trees, one of the most successful and prominent mutualisms of the neotropics. These pioneer plants provide hollow internodes for nesting and nutrient-rich food bodies; in return, the ants provide protection from herbivores and encroaching vines. I first explored the structure of the behavioral syndrome by testing the consistency and correlation of colony-level behavioral traits under natural conditions in the field. Traits were both consistent within colonies and correlated among colonies revealing a behavioral syndrome along a docile-aggressive axis. Host plants of more active, aggressive colonies had less leaf damage, suggesting a link between a colony personality and host plant health. I then studied how aspects of colony sociometry are intertwined with their host plants by assessing the relationship among plant growth, colony growth, colony structure, ant morphology, and colony personality. Colony personality was independent of host plant measures like tree size, age, volume. Finally, I tested how colony personality influenced by soil nutrients by assessing personality in the field and transferring colonies to plants the greenhouse under different soil nutrient treatments. Personality was correlated with soil nutrients in the field but was not influenced by soil nutrient treatment in the greenhouse. This suggests that soil nutrients interact with other factors in the environment to structure personality. This dissertation demonstrates that colony personality is an ecologically relevant phenomenon and an important consideration for mutualism dynamics.
ContributorsMarting, Peter (Author) / Pratt, Stephen C (Thesis advisor) / Wcislo, William T (Committee member) / Hoelldobler, Bert (Committee member) / Fewell, Jennifer H (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2018