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Foraging has complex effects on whole-organism homeostasis, and there is considerable evidence that foraging behavior is influenced by both environmental factors (e.g., food availability, predation risk) and the physiological condition of an organism. The optimization of foraging behavior to balance costs and benefits is termed state-dependent foraging (SDF) while behavior

Foraging has complex effects on whole-organism homeostasis, and there is considerable evidence that foraging behavior is influenced by both environmental factors (e.g., food availability, predation risk) and the physiological condition of an organism. The optimization of foraging behavior to balance costs and benefits is termed state-dependent foraging (SDF) while behavior that seeks to protect assets of fitness is termed the asset protection principle (APP). A majority of studies examining SDF have focused on the role that energy balance has on the foraging of organisms with high metabolism and high energy demands ("high-energy systems" such as endotherms). In contrast, limited work has examined whether species with low energy use ("low-energy systems" such as vertebrate ectotherms) use an SDF strategy. Additionally, there is a paucity of evidence demonstrating how physiological and environmental factors other than energy balance influence foraging behavior (e.g. hydration state and free-standing water availability). Given these gaps in our understanding of SDF behavior and the APP, I examined the state-dependency and consequences of foraging in a low-energy system occupying a resource-limited environment - the Gila monster (Heloderma suspectum, Cope 1869). In contrast to what has been observed in a wide variety of taxa, I found that Gila monsters do not use a SDF strategy to manage their energy reserves and that Gila monsters do not defend their energetic assets. However, hydration state and free-standing water availability do affect foraging behavior of Gila monsters. Additionally, as Gila monsters become increasingly dehydrated, they reduce activity to defend hydration state. The SDF behavior of Gila monsters appears to be largely driven by the fact that Gila monsters must separately satisfy energy and water demands with food and free-standing water, respectively, in conjunction with the timescale within which Gila monsters balance their energy and water budgets (supra-annually versus annually, respectively). Given these findings, the impact of anticipated changes in temperature and rainfall patterns in the Sonoran Desert are most likely going to pose their greatest risks to Gila monsters through the direct and indirect effects on water balance.
ContributorsWright, Christian (Author) / Denardo, Dale F. (Thesis advisor) / Harrison, Jon (Committee member) / McGraw, Kevin (Committee member) / Sullivan, Brian (Committee member) / Wolf, Blair (Committee member) / Arizona State University (Publisher)
Created2014
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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

Consideration of both biological and human-use dynamics in coupled social-ecological systems is essential for the success of interventions such as marine reserves. As purely human institutions, marine reserves have no direct effects on ecological systems. Consequently, the success of a marine reserve depends on managers` ability to alter human behavior in the direction and magnitude that supports reserve objectives. Further, a marine reserve is just one component in a larger coupled social-ecological system. The social, economic, political, and biological landscape all determine the social acceptability of a reserve, conflicts that arise, how the reserve interacts with existing fisheries management, accuracy of reserve monitoring, and whether the reserve is ultimately able to meet conservation and fishery enhancement goals. Just as the social-ecological landscape is critical at all stages for marine reserve, from initial establishment to maintenance, the reserve in turn interacts with biological and human use dynamics beyond its borders. Those interactions can lead to the failure of a reserve to meet management goals, or compromise management goals outside the reserve. I use a bio-economic model of a fishery in a spatially patchy environment to demonstrate how the pre-reserve fisheries management strategy determines the pattern of fishing effort displacement once the reserve is established, and discuss the social, political, and biological consequences of different patterns for the reserve and the fishery. Using a stochastic bio-economic model, I demonstrate how biological and human use connectivity can confound the accurate detection of reserve effects by violating assumptions in the quasi-experimental framework. Finally, I examine data on recreational fishing site selection to investigate changes in response to the announcement of enforcement of a marine reserve in the Gulf of California, Mexico. I generate a scale of fines that would fully or partially protect the reserve, providing a data-driven way for managers to balance biological and socio-economic goals. I suggest that natural resource managers consider human use dynamics with the same frequency, rigor, and tools as they do biological stocks.
ContributorsFujitani, Marie (Author) / Abbott, Joshua (Thesis advisor) / Fenichel, Eli (Thesis advisor) / Gerber, Leah (Committee member) / Anderies, John (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The bleomycins are a family of glycopeptide-derived antibiotics isolated from various Streptomyces species and have been the subject of much attention from the scientific community as a consequence of their antitumor activity. Bleomycin clinically and is an integral part of a number of combination chemotherapy regimens. It has previously been

The bleomycins are a family of glycopeptide-derived antibiotics isolated from various Streptomyces species and have been the subject of much attention from the scientific community as a consequence of their antitumor activity. Bleomycin clinically and is an integral part of a number of combination chemotherapy regimens. It has previously been shown that bleomycin has the ability to selectively target tumor cells over their non-malignant counterparts. Pyrimidoblamic acid, the N-terminal metal ion binding domain of bleomycin is known to be the moiety that is responsible for O2 activation and the subsequent chemistry leading to DNA strand scission and overall antitumor activity. Chapter 1 describes bleomycin and related DNA targeting antitumor agents as well as the specific structural domains of bleomycin. Various structural analogues of pyrimidoblamic acid were synthesized and subsequently incorporated into their corresponding full deglycoBLM A6 derivatives by utilizing a solid support. Their activity was measured using a pSP64 DNA plasmid relaxation assay and is summarized in Chapter 2. The specifics of bleomycin—DNA interaction and kinetics were studied via surface plasmon resonance and are presented in Chapter 3. By utilizing carefully selected 64-nucleotide DNA hairpins with variable 16-mer regions whose sequences showed strong binding in past selection studies, a kinetic profile was obtained for several BLMs for the first time since bleomycin was discovered in 1966. The disaccharide moiety of bleomycin has been previously shown to be a specific tumor cell targeting element comprised of L-gulose-D-mannose, especially between MCF-7 (breast cancer cells) and MCF-10A ("normal" breast cells). This phenomenon was further investigated via fluorescence microscopy using multiple cancerous cell lines with matched "normal" counterparts and is fully described in Chapter 4.
ContributorsBozeman, Trevor C (Author) / Hecht, Sidney M. (Thesis advisor) / Chaput, John (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2013
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Description
DNA is a unique, highly programmable and addressable biomolecule. Due to its reliable and predictable base recognition behavior, uniform structural properties, and extraordinary stability, DNA molecules are desirable substrates for biological computation and nanotechnology. The field of DNA computation has gained considerable attention due to the possibility of exploiting the

DNA is a unique, highly programmable and addressable biomolecule. Due to its reliable and predictable base recognition behavior, uniform structural properties, and extraordinary stability, DNA molecules are desirable substrates for biological computation and nanotechnology. The field of DNA computation has gained considerable attention due to the possibility of exploiting the massive parallelism that is inherent in natural systems to solve computational problems. This dissertation focuses on building novel types of computational DNA systems based on both DNA reaction networks and DNA nanotechnology. A series of related research projects are presented here. First, a novel, three-input majority logic gate based on DNA strand displacement reactions was constructed. Here, the three inputs in the majority gate have equal priority, and the output will be true if any two of the inputs are true. We subsequently designed and realized a complex, 5-input majority logic gate. By controlling two of the five inputs, the complex gate is capable of realizing every combination of OR and AND gates of the other 3 inputs. Next, we constructed a half adder, which is a basic arithmetic unit, from DNA strand operated XOR and AND gates. The aim of these two projects was to develop novel types of DNA logic gates to enrich the DNA computation toolbox, and to examine plausible ways to implement large scale DNA logic circuits. The third project utilized a two dimensional DNA origami frame shaped structure with a hollow interior where DNA hybridization seeds were selectively positioned to control the assembly of small DNA tile building blocks. The small DNA tiles were directed to fill the hollow interior of the DNA origami frame, guided through sticky end interactions at prescribed positions. This research shed light on the fundamental behavior of DNA based self-assembling systems, and provided the information necessary to build programmed nanodisplays based on the self-assembly of DNA.
ContributorsLi, Wei (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Chen, Julian (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2014
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Description
As an evolutionary force, hybridization outcomes include introgression, admixture, speciation, and reproductive isolation. While hybridization has been studied in several primates, the marmoset genus Callithrix is an important, but little studied example of Neotropical hybridization. Varying degrees of reproductive isolation exist between Callithrix species, and hybridization occurs at species borders

As an evolutionary force, hybridization outcomes include introgression, admixture, speciation, and reproductive isolation. While hybridization has been studied in several primates, the marmoset genus Callithrix is an important, but little studied example of Neotropical hybridization. Varying degrees of reproductive isolation exist between Callithrix species, and hybridization occurs at species borders or regions containing introduced and native species. Interbreeding between Callithrix species carries important implications for biodiversity and genetic integrity within the genus. However, species origins and levels of genetic admixture in marmoset hybrid zones are generally unknown, and few population genetic studies of individual Callithrix species exist. Using the mitochondrial control region and 44 microsatellite markers, this work explored the genetic diversity and species origins of two C. penicillata and C. jacchus hybrid zones, as well as genetic diversity and divergence in the parental species. Both marker types showed that C. penicillata is more genetically diverse than C. jacchus. Based on mtDNA, C. jacchus seems to have experienced a past population expansion and C. penicillata evolved under constant population size. The data revealed the existence of a previously undocumented natural hybrid zone along the São Francisco River in NE Brazil and confirmed species origins of an anthropogenic zone in Rio de Janeiro state. The data also showed much lower levels of admixture and genetic diversity within the natural hybrid zone than in the anthropogenic zone. Further, the data suggested that the São Francisco River is an important geographic barrier to gene flow in the natural hybrid zone. On the other hand, admixture patterns within the anthropogenic hybrid zone suggested collapse of reproductive barriers, and the formation of a hybrid marmoset swarm. Thus, this work suggested different evolutionary dynamics in anthropogenic vs. natural animal hybrid zones. Restriction Associated DNA sequencing (RADseq) identified a large number of single nucleotide polymorphisms within C. jacchus and C. penicillata genomes. These preliminary data were used to measure intraspecific genomic diversity and interspecific divergence. In the future, RADseq will be used to study genus-wide diversity of Callithrix species, examine past and present marmoset demographic history, and applied to the evolutionary study of marmoset hybridization.
ContributorsMalukiewicz, Joanna (Author) / Stone, Anne C. (Thesis advisor) / Nash, Leanne (Committee member) / Rosenberg, Michael (Committee member) / Hedrick, Phil (Committee member) / Ruiz-Miranda, Carlo (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e.,

Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Urbanization provides an excellent opportunity to examine the effects of human-induced rapid environmental change (HIREC) on natural ecosystems. Certain species can dominate in urban habitats at the expense of biodiversity. Phenotypic plasticity may be the mechanism by which these 'urban exploiters' flourish in urban areas. Color displays and condition-dependent phenotypes

Urbanization provides an excellent opportunity to examine the effects of human-induced rapid environmental change (HIREC) on natural ecosystems. Certain species can dominate in urban habitats at the expense of biodiversity. Phenotypic plasticity may be the mechanism by which these 'urban exploiters' flourish in urban areas. Color displays and condition-dependent phenotypes are known to be highly plastic. However, conspicuous color displays are perplexing in that they can be costly to produce and may increase detection by enemies. The Western black widow spider () is a superabundant pest species that forms dense aggregations throughout metropolitan Phoenix, Arizona, USA. Adult female display a red hourglass on their abdomen, which is speculated to function as a conspicuous warning signal to enemies. Here, I performed field studies to identify how widow morphology and hourglass color differ between urban and desert subpopulations. I also conducted laboratory experiments to examine the dietary sensitivity of hourglass coloration and to identify its functional role in the contexts of agonism, mating, and predator defense. My field data reveal significant spatial variation across urban and desert subpopulations in ecology and color. Furthermore, hourglass coloration was significantly influenced by environmental factors unique to urban habitats. Desert spiders were found to be smaller and less colorful than urban spiders. Throughout, I observed a positive correlation between body condition and hourglass size. Laboratory diet manipulations empirically confirm the condition-dependence of hourglass size. Additionally, widows with extreme body conditions exhibited condition-dependent coloration. However, hourglass obstruction and enlargement did not produce any effects on the outcome of agonistic encounters, male courtship, or predator deterrence. This work offers important insights into the effects of urbanization on the ecology and coloration of a superabundant pest species. While the function of the hourglass remains undetermined, my findings characterize the black widow's hourglass as extremely plastic. Plastic responses to novel environmental conditions can modify the targets of natural selection and subsequently influence evolutionary outcomes. Therefore, assuming a heritable component to this plasticity, the response of hourglass plasticity to the abrupt environmental changes in urban habitats may result in the rapid evolution of this phenotype.
ContributorsGburek, Theresa (Author) / Johnson, James C. (Thesis advisor) / McGraw, Kevin J. (Committee member) / Rutowski, Ronald L (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Rapid and reliable separation and analysis of proteins require powerful analytical methods. The analysis of proteins becomes especially challenging when only small sample volumes are available, concomitantly with low concentrations of proteins. Time critical situations pose additional challenges. Due to these challenges, conventional macro-scale separation techniques reach their limitations. While

Rapid and reliable separation and analysis of proteins require powerful analytical methods. The analysis of proteins becomes especially challenging when only small sample volumes are available, concomitantly with low concentrations of proteins. Time critical situations pose additional challenges. Due to these challenges, conventional macro-scale separation techniques reach their limitations. While microfluidic devices require only pL-nL sample volumes, they offer several advantages such as speed, efficiency, and high throughput. This work elucidates the capability to manipulate proteins in a rapid and reliable manner with a novel migration technique, namely dielectrophoresis (DEP). Since protein analysis can often be achieved through a combination of orthogonal techniques, adding DEP as a gradient technique to the portfolio of protein manipulation methods can extend and improve combinatorial approaches. To this aim, microfluidic devices tailored with integrated insulating obstacles were fabricated to create inhomogeneous electric fields evoking insulator-based DEP (iDEP). A main focus of this work was the development of pre-concentration devices where topological micropost arrays are fabricated using standard photo- and soft lithographic techniques. With these devices, positive DEP-driven streaming of proteins was demonstrated for the first time using immunoglobulin G (IgG) and bovine serum albumin. Experimentally observed iDEP concentrations of both proteins were in excellent agreement with positive DEP concentration profiles obtained by numerical simulations. Moreover, the micropost iDEP devices were improved by introducing nano-constrictions with focused ion beam milling with which numerical simulations suggested enhancement of the DEP effect, leading to a 12-fold increase in concentration of IgG. Additionally, concentration of β-galactosidase was observed, which seems to occur due to an interplay of negative DEP, electroosmosis, electrokinesis, diffusion, and ion concentration polarization. A detailed study was performed to investigate factors influencing protein DEP under DC conditions, including electroosmosis, electrophoresis, and Joule heating. Specifically, temperature rise within the iDEP device due to Joule heating was measured experimentally with spatial and temporal resolution by employing the thermosensitive dye Rhodamine B. Unlike DNA and cells, protein DEP behavior is not well understood to date. Therefore, this detailed study of protein DEP provides novel information to eventually optimize this protein migration method for pre-concentration, separation, and fractionation.
ContributorsNakano, Asuka (Author) / Ros, Alexandra (Thesis advisor) / Hayes, Mark (Committee member) / Levitus, Marcia (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive

The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The coordination of group behavior in the social insects is representative of a broader phenomenon in nature, emergent biological complexity. In such systems, it is believed that large-scale patterns result from the interaction of relatively simple subunits. This dissertation involved the study of one such system: the social foraging of

The coordination of group behavior in the social insects is representative of a broader phenomenon in nature, emergent biological complexity. In such systems, it is believed that large-scale patterns result from the interaction of relatively simple subunits. This dissertation involved the study of one such system: the social foraging of the ant Temnothorax rugatulus. Physically tiny with small population sizes, these cavity-dwelling ants provide a good model system to explore the mechanisms and ultimate origins of collective behavior in insect societies. My studies showed that colonies robustly exploit sugar water. Given a choice between feeders unequal in quality, colonies allocate more foragers to the better feeder. If the feeders change in quality, colonies are able to reallocate their foragers to the new location of the better feeder. These qualities of flexibility and allocation could be explained by the nature of positive feedback (tandem run recruitment) that these ants use. By observing foraging colonies with paint-marked ants, I was able to determine the `rules' that individuals follow: foragers recruit more and give up less when they find a better food source. By altering the nutritional condition of colonies, I found that these rules are flexible - attuned to the colony state. In starved colonies, individual ants are more likely to explore and recruit to food sources than in well-fed colonies. Similar to honeybees, Temmnothorax foragers appear to modulate their exploitation and recruitment behavior in response to environmental and social cues. Finally, I explored the influence of ecology (resource distribution) on the foraging success of colonies. Larger colonies showed increased consistency and a greater rate of harvest than smaller colonies, but this advantage was mediated by the distribution of resources. While patchy or rare food sources exaggerated the relative success of large colonies, regularly (or easily found) distributions leveled the playing field for smaller colonies. Social foraging in ant societies can best be understood when we view the colony as a single organism and the phenotype - group size, communication, and individual behavior - as integrated components of a homeostatic unit.
ContributorsShaffer, Zachary (Author) / Pratt, Stephen C (Thesis advisor) / Hölldobler, Bert (Committee member) / Janssen, Marco (Committee member) / Fewell, Jennifer (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2014