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- Creators: Arizona State University
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Description
Coccidioidomycosis, also known as Valley Fever, is a disease caused by the dimorphic soil-dwelling fungus, Coccidioides sp. Coccidioidomycosis is difficult to diagnose because symptoms are similar to community-acquired pneumonia. Current diagnostic tests rely on antibody responses, but immune responses can be delayed and aberrant, resulting in false negative diagnoses. Unlike serology, detection of coccidioidal proteins or other fungal components in blood could distinguish valley fever from other pulmonary infections and provide a definitive diagnosis. Using mass spectrometry (LC-MS/MS) we examined the plasma peptidome from patients with serologically confirmed coccidioidomycosis. Mass spectra were searched using the protein database from the Coccidioides species, generated and annotated by the Broad Institute. 15 of 20 patients with serologically confirmed coccidioidomycosis demonstrated the presence of a peptide in plasma, "PGLDSKSLACTFSQV" (PGLD). The peptide is derived from an open reading frame from a "conserved hypothetical protein" annotated with 2 exons, and to date, found only in the C. posadasii strain Silviera RMSCC 3488 genomic sequence. In this thesis work, cDNA sequence analysis from polyadenylated RNA confirms the peptide sequence and genomic location of the peptide, but does not indicate that the intron in the gene prediction of C. posadasii strain Silviera RMSCC 3488 is present. A monoclonal antibody generated against the peptide bound to a 16kDa protein in T27K coccidioidal lysate. Detecting components of the fungus plasma could be a useful diagnostic tool, especially when serology does not provide a definitive diagnosis.
ContributorsDuffy, Stacy Leigh (Author) / Lake, Douglas (Thesis advisor) / Magee, Dewey Mitch (Committee member) / Antwi, Kwasi (Committee member) / Arizona State University (Publisher)
Created2013
Description
Speciation is the fundamental process that has generated the vast diversity of life on earth. The hallmark of speciation is the evolution of barriers to gene flow. These barriers may reduce gene flow either by keeping incipient species from hybridizing at all (pre-zygotic), or by reducing the fitness of hybrids (post-zygotic). To understand the genetic architecture of these barriers and how they evolve, I studied a genus of wasps that exhibits barriers to gene flow that act both pre- and post-zygotically. Nasonia is a genus of four species of parasitoid wasps that can be hybridized in the laboratory. When two of these species, N. vitripennis and N. giraulti are mated, their offspring suffer, depending on the generation and cross examined, up to 80% mortality during larval development due to incompatible genic interactions between their nuclear and mitochondrial genomes. These species also exhibit pre-zygotic isolation, meaning they are more likely to mate with their own species when given the choice. I examined these two species and their hybrids to determine the genetic and physiological bases of both speciation mechanisms and to understand the evolutionary forces leading to them. I present results that indicate that the oxidative phosphorylation (OXPHOS) pathway, an essential pathway that is responsible for mitochondrial energy generation, is impaired in hybrids of these two species. These results indicate that this impairment is due to the unique evolutionary dynamics of the combined nuclear and mitochondrial origin of this pathway. I also present results showing that, as larvae, these hybrids experience retarded growth linked to the previously observed mortality and I explore possible physiological mechanisms for this. Finally, I show that the pre-mating isolation is due to a change in a single pheromone component in N. vitripennis males, that this change is under simple genetic control, and that it evolved neutrally before being co-opted as a species recognition signal. These results are an important addition to our overall understanding of the mechanisms of speciation and showcase Nasonia as an emerging model for the study of the genetics of speciation.
ContributorsGibson, Joshua D (Author) / Gadau, Jürgen (Thesis advisor) / Harrison, Jon (Committee member) / Pratt, Stephen (Committee member) / Verrelli, Brian (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
Modified and artificial water sources can be used as a management tool for game and non-game wildlife species. State, federal, and private agencies allocate significant resources to install and maintain artificial water sources (AWS) annually. Capture mark recapture methods were used to sample small mammal communities in the vicinity of five AWS and five paired control sites (treatments) in the surrounding Sonoran desert from October 2011 to May 2012. I measured plant species richness, density, and percent cover in the spring of 2012. A Multi-response Permutation Procedure was used to identify differences in small mammal community abundance, biomass, and species richness by season and treatment. I used Principle Component Analysis to reduce 11 habitat characteristics to five habitat factors. I related rodent occurrence to habitat characteristics using multiple and logistic regression. A total of 370 individual mammals representing three genera and eight species of rodents were captured across 4800 trap nights. Desert pocket mouse (Chaetodipus penicillatus) was the most common species in both seasons and treatments. Whereas rodent community abundance, biomass, and richness were similar between seasons, community variables of AWS were greater than CS. Rodent diversity was similar between treatments. Desert pocket mouse abundance and biomass were twice as high at AWS when compared to controls. Biomass of white-throated woodrat (Neotoma albigula) was five times greater at AWS. Habitat characteristics were similar between treatments. Neither presence of water nor distance to water explained substantial habitat variation. Occurrence of rodent species was associated with habitat characteristics. Desert rodent communities are adapted for arid environments (i.e. Heteromyids) and are not dependent on "free water". Higher abundances of desert pocket mouse at AWS were most likely related to increased disturbance and debris and not the presence of water. The results of this study and previous studies suggest that more investigation is needed and that short term studies may not be able to detect interactions (if any) between AWS and desert small mammal communities.
ContributorsSwitalski, Aaron (Author) / Bateman, Heather L (Thesis advisor) / Miller, William (Committee member) / Alford, Eddie (Committee member) / Arizona State University (Publisher)
Created2013
Description
The academic literature on science communication widely acknowledges a problem: science communication between experts and lay audiences is important, but it is not done well. General audience popular science books, however, carry a reputation for clear science communication and are understudied in the academic literature. For this doctoral dissertation, I utilize Sam Harris's The Moral Landscape, a general audience science book on the particularly thorny topic of neuroscientific approaches to morality, as a case-study to explore the possibility of using general audience science books as models for science communication more broadly. I conduct a literary analysis of the text that delimits the scope of its project, its intended audience, and the domains of science to be communicated. I also identify seven literary aspects of the text: three positive aspects that facilitate clarity and four negative aspects that interfere with lay public engagement. I conclude that The Moral Landscape relies on an assumed knowledge base and intuitions of its audience that cannot reasonably be expected of lay audiences; therefore, it cannot properly be construed as popular science communication. It nevertheless contains normative lessons for the broader science project, both in literary aspects to be salvaged and literary aspects and concepts to consciously be avoided and combated. I note that The Moral Landscape's failings can also be taken as an indication that typical descriptions of science communication offer under-detailed taxonomies of both audiences for science communication and the varieties of science communication aimed at those audiences. Future directions of study include rethinking appropriate target audiences for science literacy projects and developing a more discriminating taxonomy of both science communication and lay publics.
ContributorsJohnson, Nathan W (Author) / Robert, Jason S (Thesis advisor) / Creath, Richard (Committee member) / Martinez, Jacqueline (Committee member) / Sylvester, Edward (Committee member) / Lynch, John (Committee member) / Arizona State University (Publisher)
Created2013
Description
Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments in cell degeneration research with the four major chapters, I trace the emergence of the degenerating cell as a scientific object, describe the generations of a variety of concepts, interpretations and usages associated with cell death and aging, and analyze the transforming influences of the rising cell degeneration research. Particularly, the four chapters show how the changing scientific practices about cellular life in embryology, cell culture, aging research, and molecular biology of Caenorhabditis elegans shaped the interpretations about cell degeneration in the twentieth-century as life-shaping, limit-setting, complex, yet regulated. These events created and consolidated important concepts in life sciences such as programmed cell death, the Hayflick limit, apoptosis, and death genes. These cases also transformed the material and epistemic practices about the end of cellular life subsequently and led to the formations of new research communities. The four cases together show the ways cell degeneration became a shared subject between molecular cell biology, developmental biology, gerontology, oncology, and pathology of degenerative diseases. These practices and perspectives created a special kind of interconnectivity between different fields and led to a level of interdisciplinarity within cell degeneration research by the early 1990s.
ContributorsJiang, Lijing (Author) / Maienschein, Jane (Thesis advisor) / Laubichler, Manfred (Thesis advisor) / Hurlbut, James (Committee member) / Creath, Richard (Committee member) / White, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
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
Description
Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
To address the need of scientists and engineers in the United States workforce and ensure that students in higher education become scientifically literate, research and policy has called for improvements in undergraduate education in the sciences. One particular pathway for improving undergraduate education in the science fields is to reform undergraduate teaching. Only a limited number of studies have explored the pedagogical content knowledge of postsecondary level teachers. This study was conducted to characterize the PCK of biology faculty and explore the factors influencing their PCK. Data included semi-structured interviews, classroom observations, documents, and instructional artifacts. A qualitative inquiry was designed to conduct an in-depth investigation focusing on the PCK of six biology instructors, particularly the types of knowledge they used for teaching biology, their perceptions of teaching, and the social interactions and experiences that influenced their PCK. The findings of this study reveal that the PCK of the biology faculty included eight domains of knowledge: (1) content, (2) context, (3) learners and learning, (4) curriculum, (5) instructional strategies, (6) representations of biology, (7) assessment, and (8) building rapport with students. Three categories of faculty PCK emerged: (1) PCK as an expert explainer, (2) PCK as an instructional architect, and (3) a transitional PCK, which fell between the two prior categories. Based on the interpretations of the data, four social interactions and experiences were found to influence biology faculty PCK: (1) teaching experience, (2) models and mentors, (3) collaborations about teaching, and (4) science education research. The varying teaching perspectives of the faculty also influenced their PCK. This study shows that the PCK of biology faculty for teaching large introductory courses at large research institutions is heavily influenced by factors beyond simply years of teaching experience and expert content knowledge. Social interactions and experiences created by the institution play a significant role in developing the PCK of biology faculty.
ContributorsHill, Kathleen M. (Author) / Luft, Julie A. (Thesis advisor) / Baker, Dale (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Liquid-liquid interfaces serve as ideal 2-D templates on which solid particles can self-assemble into various structures. These self-assembly processes are important in fabrication of micron-sized devices and emulsion formulation. At oil/water interfaces, these structures can range from close-packed aggregates to ordered lattices. By incorporating an ionic liquid (IL) at the interface, new self-assembly phenomena emerge. ILs are ionic compounds that are liquid at room temperature (essentially molten salts at ambient conditions) that have remarkable properties such as negligible volatility and high chemical stability and can be optimized for nearly any application. The nature of IL-fluid interfaces has not yet been studied in depth. Consequently, the corresponding self-assembly phenomena have not yet been explored. We demonstrate how the unique molecular nature of ILs allows for new self-assembly phenomena to take place at their interfaces. These phenomena include droplet bridging (the self-assembly of both particles and emulsion droplets), spontaneous particle transport through the liquid-liquid interface, and various gelation behaviors. In droplet bridging, self-assembled monolayers of particles effectively "glue" emulsion droplets to one another, allowing the droplets to self-assembly into large networks. With particle transport, it is experimentally demonstrated the ILs overcome the strong adhesive nature of the liquid-liquid interface and extract solid particles from the bulk phase without the aid of external forces. These phenomena are quantified and corresponding mechanisms are proposed. The experimental investigations are supported by molecular dynamics (MD) simulations, which allow for a molecular view of the self-assembly process. In particular, we show that particle self-assembly depends primarily on the surface chemistry of the particles and the non-IL fluid at the interface. Free energy calculations show that the attractive forces between nanoparticles and the liquid-liquid interface are unusually long-ranged, due to capillary waves. Furthermore, IL cations can exhibit molecular ordering at the IL-oil interface, resulting in a slight residual charge at this interface. We also explore the transient IL-IL interface, revealing molecular interactions responsible for the unusually slow mixing dynamics between two ILs. This dissertation, therefore, contributes to both experimental and theoretical understanding of particle self-assembly at IL based interfaces.
ContributorsFrost, Denzil (Author) / Dai, Lenore L (Thesis advisor) / Torres, César I (Committee member) / Nielsen, David R (Committee member) / Squires, Kyle D (Committee member) / Rege, Kaushal (Committee member) / Arizona State University (Publisher)
Created2013
Description
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